After being injected with the telomerase gene, adult and old mice lived 24 percent and 13 percent longer, respectively.

Scientists are doing their best to give us the gift of immortality. The latest in the fight against ever dying is a gene therapy that gives mice a healthy dose of telomerase, the enzyme that keeps our chromosomes – and thus our cells and bodies – “young.” The therapy extended the lifespans of mice by 24 percent and, at least so far, the therapy appears to be completely safe.

As we age the dying cells in our body are replenished through cell division. But with each cell division the bits of DNA at the ends of chromosomes – the telomeres – deteriorate. At some point the shortened telomeres signal to the cell that it’s time to stop dividing, leading to tissue degradation – one of the hard facts of life for the now aged cells. But now scientists have given cells a kind of molecular fountain of youth – at least in mice. They injected the mice with the telomerase gene which then slowed the cellular aging process by extending the dwindling telomere ends. They gave the gene therapy to one year old mice, considered adults, and two year old mice, considered old. The lifespan of the one year olds were extended by 24 percent, the two year olds by 13 percent. Not only did the mice live longer, but they reaped beneficial effects across a range of conditions associated with aging including insulin sensitivity, osteoporosis, and physical coordination.

An inactive form of telomerase had no effect on lifespan, confirming that its telomere-lengthening enzymatic activity was crucial. The study was led by María Blasco at the Spanish National Cancer Research Centre and published in EMBO Molecular Medicine.

Dr. Marìa Blasco, Spanish National Cancer Research Centre

The treatment involved replacing the genes of a virus with the gene for telomerase. This viral vector had several advantages. First, viruses are good at getting into the body and infecting a large number of cells. Inserting telomerase into a small handful of cells won’t have much impact on an organism’s lifespan. Second, the gene remains active for years. And lastly, the viral DNA did not insert itself into the DNA of the mouse cells. Past attempts at gene therapy that work this way run the risk of insertion errors that turn the cell into a tumor, as was the case in the trial which caused leukemia in two of nine participants testing a gene therapy for “bubble boy disease.”

Longevity through telomerase is nothing new. Adding telomerase to human cells in culture allowed them to extend their lifespans by at least an extra 20 divisions. And mice genetically engineered to make telomerase lived 40 percent longer and showed improved glucose tolerance, coordination, and less inflammation compared to normal mice. But genetically engineering people isn’t an option (yet), so a treatment form of telomerase such as the injectable virus in the current study – extending the lifespans of adult and old mice – is a much more conceivable approach.

Aging is a complex process with lots of components, many of which we might not even be aware. But if telomere shortening is really so powerfully rate-limiting to our lifespans, then it could turn out to be as close to a silver bullet for longevity as we’re likely to find. Maybe telomerase treatments could buy us those extra years crucial to reaching Aubrey de Grey’s “longevity escape velocity” beyond which new treatments will save us from the disease of death – indefinitely.

[image credits: Science Daily, publico.es, and Science Creative Daily]
images: Science Daily, publico.es, Science Creative Daily

Small molecule, big controversy. A new study clears doubts about how resveratrol causes its anti-aging effects.

Resveratrol, the famed anti-aging supplement extracted from red wine, has experienced its share of controversy. An experimental artifact, a pair of studies that questioned its health benefits, and the shady practices of one now-discredited scientist have put resveratrol in a bad light as of late. But a recent study now attempts to help set the record straight by confirming one part of the resveratrol puzzle.

Resveratrol was first identified in 2003 when Konrad Howitz, working with David Sinclair’s group at Harvard, found that it activated the protein SIRT1. Past research has “implicated” SIRT1 as an anti-aging factor due to the beneficial effects it has on glucose homeostasis, neurodegeneration, and integrity of the cell’s power house, the mitochondria. A number of studies suggested that the healthful benefits of resveratrol were via the activation of SIRT1 but it still remained to be shown convincingly. Even casting doubt on resveratrol’s ability to activate SIRT1 were two 2005 studies that showed that a fluorescent marker used in one of the experiments was activating SIRT1 itself.

To get to the molecular bottom of things, Harvard biologist David Sinclair and his team devised an elegant experiment to see if resveratrol still had the same effect on cells if SIRT1 was removed. This would be a convincing demonstration that the beneficial effects of resveratrol were indeed through the activation of SIRT1. To do this the group developed a mouse that was genetically modified so that all of the SIRT1 in its body would disappear when it was given a certain chemical. Strikingly, normal mice in the study reaped the expected benefits when given resveratrol, but mice with no SIRT1 did not.

Sinclair co-founded Sirtis Pharmaceuticals, which is developing drugs that, like resveratrol, activate SIRT1, so obviously data supporting that the benefits of resveratrol are via SIRT1 activation helps out Sinclair and other companies developing drugs meant to mimic resveratrol or otherwise activate SIRT1. Conversely, we previously pointed out that two studies which put into question resveratrol’s beneficial effects were performed by Pfizer and Amgen, companies in competition with Glaxo-Smith-Kline who bought Sirtis in 2008 for $720 million.

Does the potential conflict of interest detract from the powerful demonstration Sinclair’s team was able to show with their genetically-modified mice?  There are sure to be more pieces to the resveratrol puzzle and the current experiment will have to be reproduced. But for the moment, demonstrating the link between the wine extract and SIRT1 is an important step if resveratrol will ever be shown to live up to its anti-aging potential.

[image credits: LA Times and extremelongevity.net]
images: wine and molecule

Amyvid, a drug that binds to a marker for Alzheimer's disease, gives physicians a new tool with which to differentiate between normal (left) and Alzheimer's (right) individuals.

Pharmaceutical giant Eli Lily just got FDA approval on a chemical that would enable clinicians to detect a biological marker for Alzheimer’s disease. They can detect the marker now, but currently quantifying it can only be performed during autopsy. Detecting it early, during a person’s lifetime has the potential to not only identify people at risk for Alzheimer’s before they show symptoms, but it could help researchers searching for a cure.

The chemical, called florbetapir or its brand name Amyvid, binds to the protein, beta-amyloid, thought to be a hallmark of Alzheimer’s disease. The drug, which is radioactive, is injected into patients which are then imaged with a Positron Emission Tomography (PET) scan that detects the radioactive signal. A positive scan means there are at least a moderate amount of amyloid plaques, the aggregates of amyloid protein thought to disrupt neuronal function and lead to cognitive decline and dementia associated with Alzheimer’s disease.

Right now Alzheimer’s disease is diagnosed by individual physicians who detect cognitive and behavioral changes in the patient. But by the time behavioral changes are evident, scientists think, the disease is already very advanced. They think that the disease actually begins years before symptoms start to show. If there was a way to detect the disease, such as a PET scan that detects an increase in amyloid protein, doctors could identify high risk patients years before they begin to show symptoms.

Unfortunately, that won’t help the patients very much as there is currently no cure for Alzheimer’s disease. But the real strength of the test rests in its ability to differentiate Alzheimer’s patients who have amyloid with those who do not.

Between 10 and 20 percent of patients diagnosed with Alzheimer’s disease do not show abnormal levels of amyloid at autopsy. The cause of the disease may be different in these patients than in the patients with elevated levels of amyloid, and thus different treatments may be required. Conducting separate studies on these two groups could be a better way to finding a cure.

Researchers also estimate that in some communities a third of patients with mild symptoms but nonetheless have Alzheimer’s disease go undiagnosed. If these patients also show increased levels of amyloid doctors may be quicker to the diagnosis.

Deaths due to Alzheimer's disease continue to rise while falling for other major diseases (source: Alzheimer's Association).

Research seeking treatment for Alzheimer’s also stands to benefit from detecting amyloid earlier. Nowadays people have to already show signs of cognitive decline to qualify for clinical trials. The problem is, the damage is already done by the time outward symptoms begin to show. If it turns out that the amount of amyloid increases appreciably before they show cognitive decline, these people at risk to develop Alzheimer’s could be enrolled in clinical trials earlier. And clinical trials aside, just correlating the timing of amyloid increase to the onset of behavioral symptoms could help researchers understand how the two are related.

Amyvid adds to the recent growth of the Alzheimer’s diagnosis toolkit. Tests, shown to be extremely accurate in differentiating Alzheimer’s and normal individuals, are already commercially available to measure amyloid from spinal fluid. A bit less traumatic than a spinal tap, a blood test was developed last year that correctly identified over 80 percent of Alzheimer’s patients based on the levels of nine hormones and proteins including amyloid. And GE Healthcare is currently developing another PET approach that uses a different tracer to bind amyloid, [(18)F] Flutemetamol. Phase III trials for the drug are underway.

Eli Lily said Amyvid will be available this June in “limited quantities.” Side effects from the drug include headache, fatigue, muscle pain, and nausea.

Alzheimer’s disease affects 54 million Americans and is the sixth-leading cause of death in the US. It is a devastating disease, not only for the victims, but their friends and family. Last year unpaid caregivers gave an estimated 17.4 billion hours towards caring for Alzheimer’s patients.

A point that is unfailingly raised in discussions about diagnosing Alzheimer’s disease is the fact that there is no cure. The few drugs that doctors prescribe are only meant to treat symptoms by improving cognitive function or decreasing anxiety. There’s a lot of people who don’t want to know if they’re at high risk for Alzheimer’s disease if they know it can’t be reversed. Fair enough. But whether or not you want to know right now, when there is a cure for Alzheimer’s, it’ll be nice to know we have tools to detect it and detect it early.

[image credits: Alzheimer's Association and modified from Journal of The American Medical Association]
[video credit: Alzheimer's Association]
images 1 and 2: JAMA
image 3: Alzheimer’s
video: Alzheimer’s by the numbers

Muscle cells taken from a cow are placed in a special nutrient mixture that promotes growth. Researchers hope to combine the cultured tissue into a hamburger sometime this fall.

A number of laboratories around the world are trying to grow meat in a Petri dish. So far we’ve heard about clumps of cells grown from stem cells with the hope that those cells will one day grow into a full-sized, grill-ready chicken fillet or hamburger. Now one researcher says the time to fire up the propane is fast approaching. Researcher Mark Post announced to his in vitro meat producing colleagues that his lab will have a hamburger fit for consumption sometime this fall.

Did you say you wanted cheese on that?

Post made the announcement a few weeks ago at the annual meeting for the American Association for the Advancement of Science in Vancouver. He said the lab is still growing the small slabs of cow skeletal muscle, but by the fall they’ll have enough tissue to piece them together into a hamburger.

Cultured meat begins with muscle cells taken from the rear of a cow for sirloin steak, for instance, or from the area surrounding a pig’s spine for growing pork chops. The cells are then placed in a nutrient mixture that helps them to proliferate. A biodegradable scaffold guides the cells as they grow together to eventually form muscle tissue. Making a hamburger requires joining these pieces of tissue into a coherent whole.

It’s unclear how long the lab has been growing their bits of burger, but given the amount of time needed to make just one hamburger we’re pretty much guaranteed a long wait before sleeves of artificially grown patties show up at the supermarket. Even if taste and nutritional value is comparable to that of normal burgers, we’re still probably years away from being able to grow cultured meat cost-effectively and in amounts large enough to make an impact on world consumption. Post’s hamburger is funded to the tune of 250,000 euros from an anonymous private investor.

But when we do, we may find ourselves at the start of a food revolution.

Late last year the Earth’s population reached 7 billion. By 2050, that number’s expected to reach 9 billion. How to feed so many people, especially countries like the US which consume twice the global average?

Population growth makes it ever more imperative to find more efficient - and more humane - ways to feed our love for meat.

In 1961 the world’s total meat supply was 71 million tons. By 2007 we were gorging more than twice that per capita and the supply had reached 284 million tons. And even though the population will increase by about a third by 2050, the world’s total meat consumption is expected to double in the same amount of time. Americans account for about 5 percent of the world’s population but eat about 15 percent of its total meat. Nearly 10 billion animals are grown and killed for food in the US each year (New York Times writer Mark Bittman specifies that the word “raise” would be incorrect to describe what happens to animals at factory farms). According to these figures, every year about 67 billion animals are slaughtered for meat worldwide.

It takes resources to sustain such prodigious numbers. Livestock production is estimated to use up 30 percent for the world’s ice-free land and produce almost a fifth of the world’s greenhouse gases, more than the amount produced by global transportation.

Needless to say, growing cultured meat in a lab would be a desirable alternative to factory farms. Not only is treating the animals more ethically and reducing carbon emissions desirable, but according to Post, cows and pigs are the least efficient among all livestock to convert to food with a bioconversion efficiency of 15 percent. PETA, obviously in favor of not killing animals for food, is encouraging scientists by offering $1 million to anyone able to bring in vitro chicken meat to the market.

Hopefully when Post’s hamburger is ready his lab will have better luck than Vladimir Mironov whose administrative run-ins kept him from a taste test last year. And if the faux burger turns out to be just as good as the real thing, overcoming the technological hurdles to producing them in a cost-effective way will be a delicious challenge I hope the whole field can’t resist.

[image credits: Reuters and National Geographic]
image 1: Mark Post
image 2: population

Life expectancy nearly doubled in developed countries over the 20th century. Prior to 1950 the increase was due mostly to a decrease in infant mortality. After the 1950s it was a decline in old age mortality that provided the main life-prolonging force. Improvements to the social and physical environments and breakthroughs in healthcare underlie both phases of mortality decrease. A person born in the US at the turn of the 20th century could expect to live 49.2 years. Their ancestor born in 2003 could reasonably expect to see their 77th birthday. But while average lifespans continue to lengthen, the oldest of the old appear to be encountering a rather powerful limiting factor. As reported recently in Slate, the number of oldest supercentenarians – people 110 and older – has stayed at around 80 over the past few years. And the age at which they die hasn’t changed over the past few decades. Data from japan is used to illustrate this. In 1990 there were 3,000 people 100 or older, the oldest of them being 114. Twenty years later the number of people aged 100 and over had grown to around 44,000, but the oldest was still 114. Robert Young, a gerontologist working for the Guinness Book of World Records, estimates that “the odds of a person dying in any given year between the ages of 110 and 113 appear to be about one in two. But by age 114, the chances jump to more like two in three.”

Number of people living to 110 years or older in Switzerland.

This phenomenon of everyone getting older but the oldest dying at the about the same age is called “rectangularization of the mortality curve.” A mortality curve tracks the probability that a person will be alive at a certain age. At birth the value is 100%. By year one it begins to slope downward, and around 70s, 80s, 90s it drops at a faster rate. In decades past the curve looked like a ski slope, hitting zero around 114. But the fact that more people are living longer lifts the curve and pushes it to the right so it looks more like a cliff than a ski slope – and more like a rectangle.

During our last Google+ Hangout we got a chance to hang with longevity researcher Aubrey de Grey, author of “Ending Aging” who once proclaimed “the first person to live to 1,000 was probably born by 1945.” We asked him about rectangularization, why it was that the whole ski slope doesn’t just move to the right but instead comes crashing down at around age 114. “This is a fascinating phenomenon and nobody has really much idea of what’s going on. What we do know is that it’s absolutely essential to not jump to conclusions about what’s going on. Time and time again over the decades past demographers have been brutally misled by short-term phenomena, by statistics gathered only over a few years. Blips happen for all manner of impenetrable reasons. In this case we’re talking about people born in a small segment of time, around 1900, and most of them born in particular countries and going through certain types of life they might not have gone through had they been born 20 years previously or 20 years later. There are many factors called ‘cohort effects’ that can cause early life phenomena to have an influence on longevity.”

Bottom line: don’t believe the hype.

“At this point I’m not exactly losing sleep over the phenomenon you’re talking about. I think that we’re probably going to see a resumption of the trend of everything just moving to the right eventually.”

Rectangularization of mortality.

De Grey also adds that medical developments could make rectangularization, much speculated upon in the study of aging, a moot discussion. “I don’t really care about whether I’m right or not about what I just said because it’s all going to become completely irrelevant when we have therapies that repair the damage of aging. Those therapies are going to make the whole concept of life expectancy…the way it’s calculated today will no longer exist.”

Because therapies will make life expectancies of the future, de Grey argues, so much longer than they are today, today’s estimates will become irrelevant. Like trying to compare Mark McGuire, Sammy Sosa and Barry Bonds to Babe Ruth. After steroids, all bets are off.

But that’s not stopping researchers from looking for the “longevity gene.” Sampling the genetic material of centenarians, researchers have seen strong correlations with several genes and the likelihood of living to 100. Two of them are involved in fat metabolism, a third in calcium metabolism.

Despite de Grey’s skepticism, if there really is a genetically-programmed limit around 114, seems to me that would make it all the more imperative to make good on the Longevity Dividend, the range of benefits to both individuals and society were we to stay healthier longer. Some argue that extending life will only postpone the inevitable disease and frailty that comes with old age. But if there were an upper bound that is not affected by current longevity trends, then the longest lifespans will not get longer but the period of age-related disease and frailty would be shortened.

Just my two cents for what they’re worth. Regardless of whether or not the upper bound is real, I agree with de Grey. Biologically, it is a fascinating phenomenon.

[image credits: dailygalaxy.com via Urban Times, Journal of Epidemiology & Community Health, and Archives of Gerentology & Geriatrics]
image 1: old age
image 2: longevity
image 3: rectangularization

With 3D printing, doctors can now create better bone implants at less cost than with conventional implants.

An 83-year-old woman suffering from a lower jaw infection became the first person to receive a jaw implant manufactured with a 3D printer. Infections such as hers are normally remedied with reconstructive surgery, but doctor’s deemed the procedure too risky because of her age and health. Instead they turned to LayerWise, a company that specializes in 3D printing of metallic structures.

Titanium powder was melted with a high-precision laser into layers guided by a computer model of the jaw. The computer model was digitally divided into 2D layers and printed at 33 layers per millimeter. The 3D printing made it possible to create an implant that just as intricate as the real thing. With articulated joints, cavities that foster muscle attachment, and grooves to guide nerve and vein regrowth, the new jaw was an intricate piece of hardware. It normally takes several days to make a custom implant, but the 3D printed implant took just a few hours to print. After the implant was made it was treated with a bioceramic coating by Cam Bioceramics BV. The surgery to attach a jaw implant normally takes around 20 hours. But because the printed implant fit so well surgeons were able to attach it in just four hours. A shorter surgery makes for a shorter recovery. The patient was able to go home with her new jaw after only four days. Normally recovery takes weeks. She was able to speak a few words after waking up, and the following day she was able to swallow again. Being made of titanium, the new jaw weighs 107 grams or about a third heavier than the patient’s own jaw. The doctors think she’ll adjust easily.

The implant is treated with a bioceramic coating prior to implantation.

The new method was made possible by research performed at the Biomed research group at the University of Hasselt in Belgium and researchers at four other universities. The surgery was performed last June but is only now being announced. Later this month the patient will undergo a follow-up surgery to remove healing implants which have served as place-holders for the patient’s teeth. After they’re removed, false teeth will be screwed into their place.

The structures that can be produced by the layer-by-layer materialization of 3D printing are practically limitless. By comparison, creating medical implants with conventional metalworking is time-consuming, expensive, and the implants don’t match the original as well. Last year an orthopedic surgeon used a 3D printer to make bone models from CT scan images that doctors could use to prepare for surgeries. Others are trying to push the medical implant envelope by printing organs! It will be a while before our bodies’ organic material will provide us a reliable ‘ink,’ says Ruben Wauthle at LayerWise, citing many biological and chemical issues that are yet unresolved. Even so, 3D printing could be a major boon for medicine in the near future. No doubt others will adopt printing for jaw and other types of bone replacements. The patients will be better off, and hospitals will save time and money.

[image credits: LayerWise]
images: LayerWise

What do you think are the odds that you will die during the next year? Try to put a number to it — 1 in 100? 1 in 10,000? Whatever it is, it will be twice as large 8 years from now.

This startling fact was first noticed by the British actuary Benjamin Gompertz in 1825 and is now called the “Gompertz Law of human mortality.” Your probability of dying during a given year doubles every 8 years. For me, a 25-year-old American, the probability of dying during the next year is a fairly miniscule 0.03% — about 1 in 3,000. When I’m 33 it will be about 1 in 1,500, when I’m 42 it will be about 1 in 750, and so on. By the time I reach age 100 (and I do plan on it) the probability of living to 101 will only be about 50%. This is seriously fast growth — my mortality rate is increasing exponentially with age.

And if my mortality rate (the probability of dying during the next year, or during the next second, however you want to phrase it) is rising exponentially, that means that the probability of me surviving to a particular age is falling super-exponentially. Below are some statistics for mortality rates in the United States in 2005, as reported by the US Census Bureau (and displayed by Wolfram Alpha):

This data fits the Gompertz law almost perfectly, with death rates doubling every 8 years. The graph on the right also agrees with the Gompertz law, and you can see the precipitous fall in survival rates starting at age 80 or so. That decline is no joke; the sharp fall in survival rates can be expressed mathematically as an exponential within an exponential:

Exponential decay is sharp, but an exponential within an exponential is so sharp that I can say with 99.999999% certainty that no human will ever live to the age of 130. (Ignoring, of course, the upward shift in the lifetime distribution that will result from future medical advances)

Surprisingly enough, the Gompertz law holds across a large number of countries, time periods, and even different species. While the actual average lifespan changes quite a bit from country to country and from animal to animal, the same general rule that “your probability of dying doubles every X years” holds true. It’s an amazing fact, and no one understands why it’s true.

There is one important lesson, however, to be learned from Benjamin Gompertz’s mysterious observation. By looking at theories of human mortality that are clearly wrong, we can deduce that our fast-rising mortality is not the result of a dangerous environment, but of a body that has a built-in expiration date.

The lightning bolt theory

If you had never seen any mortality statistics (or known very many old people), you might subscribe to what I call the “lightning bolt theory” of mortality. In this view, death is the result of a sudden and unexpected event over which you have no control. It’s sort of an ancient Greek perspective: there are angry gods carousing carelessly overhead, and every so often they hurl a lightning bolt toward Earth, which kills you if you happen to be in the wrong place at the wrong time. These are the “lightning bolts” of disease and cancer and car accidents, things that you can escape for a long time if you’re lucky but will eventually catch up to you.

The problem with this theory is that it would produce mortality rates that are nothing like what we see. Your probability of dying during a given year would be constant, and wouldn’t increase from one year to the next. Anyone who paid attention during introductory statistics will recognize that your probability of survival to age t would follow a Poisson distribution, which means exponential decay (and not super-exponential decay).

Just to make things concrete, imagine a world where every year a “lightning bolt” gets hurled in your general direction and has a 1 in 80 chance of hitting you. Your average life span will be 80 years, just like it is in the US today, but the distribution will be very different:

Your probability of survival according to the "Lightning Bolt Theory"

What a crazy world! The average lifespan would be the same, but out of every 100 people 31 would die before age 30 and 2 of them would live to be more than 300 years old. Clearly we do not live in a world where mortality is governed by “lightning bolts”.

The accumulated lightning bolt theory

I think most people will see pretty quickly why the “lightning bolt theory” is flawed. Our bodies accumulate damage as they get older. With each misfortune our defenses are weakened — a car accident might leave me paralyzed, or a knee injury could give me arthritis, or a childhood bout with pneumonia could leave me with a compromised immune system. Maybe dying is a matter of accumulating a number of “lightning strikes”; none of them individually will do you in, but the accumulated effect leads to death. I think of it something like Monty Python’s Black Knight: the first four blows are just flesh wounds, but the fifth is the end of the line.

Your probability of survival according to the "accumulated lightning bolt" theory

Fortunately, this theory is also completely testable. And, as it turns out, completely wrong. Shown above are the results from a simulated world where “lightning bolts” of misfortune hit people on average every 16 years, and death occurs at the fifth hit. This world also has an average lifespan of 80 years (16*5 = 80), and its distribution is a little less ridiculous than the previous case. Still, it’s no Gompertz Law: look at all those 160-year-olds! You can try playing around with different “lightning strike rates” and different number of hits required for death, but nothing will reproduce the Gompertz Law. No explanation based on careless gods, no matter how plentiful or how strong their blows are, will reproduce the strong upper limit to human lifespan that we actually observe.

The cops and criminals inside your body

Like I said before, no one knows why our lifespans follow the Gompertz law. But it isn’t impossible to come up with a theoretical world that follows the same law. The following argument comes from this short paper, produced by the Theoretical Physics Institute at the University of Minnesota [update: also published here in the journal Theory in Biosciences].

Imagine that within your body is an ongoing battle between cops and criminals. And, in general, the cops are winning. They patrol randomly through your body, and when they happen to come across a criminal he is promptly removed. The cops can always defeat a criminal they come across, unless the criminal has been allowed to sit in the same spot for a long time. A criminal that remains in one place for long enough (say, one day) can build a “fortress” which is too strong to be assailed by the police. If this happens, you die.

Lucky for you, the cops are plentiful, and on average they pass by every spot 14 times a day. The likelihood of them missing a particular spot for an entire day is given (as you’ve learned by now) by the Poisson distribution: it is a mere .

But what happens if your internal police force starts to dwindle? Suppose that as you age the police force suffers a slight reduction, so that they can only cover every spot 12 times a day. Then the probability of them missing a criminal for an entire day decreases to . The difference between 14 and 12 doesn’t seem like a big deal, but the result was that your chance of dying during a given day jumped by more than 10 times. And if the strength of your police force drops linearly in time, your mortality rate will rise exponentially.

This is the Gompertz law, in cartoon form: your body is deteriorating over time at a particular rate. When its “internal policemen” are good enough to patrol every spot that might contain a criminal 14 times a day, then you have the body of a 25-year-old and a 0.03% chance of dying this year. But by the time your police force can only patrol every spot 7 times per day, you have the body of a 95-year-old with only a 2-in-3 chance of making it through the year.

More questions than answers

The example above is tantalizing. The language of “cops and criminals” lends itself very easily to a discussion of the immune system fighting infection and random mutation. Particularly heartening is the fact that rates of cancer incidence also follow the Gompertz law, doubling every 8 years or so. Maybe something in the immune system is degrading over time, becoming worse at finding and destroying mutated and potentially dangerous cells.

Unfortunately, the full complexity of human biology does not lend itself readily to cartoons about cops and criminals. There are a lot of difficult questions for anyone who tries to put together a serious theory of human aging. Who are the criminals and who are the cops that kill them? What is the “incubation time” for a criminal, and why does it give “him” enough strength to fight off the immune response? Why is the police force dwindling over time? For that matter, what kind of “clock” does your body have that measures time at all?

There have been attempts to describe DNA degradation (through the shortening of your telomeres or through methylation) as an increase in “criminals” that slowly overwhelm the body’s DNA-repair mechanisms, but nothing has come of it so far. I can only hope that someday some brilliant biologist will be charmed by the simplistic physicist’s language of cops and criminals and provide us with real insight into why we age the way we do.

UPDATE: G&L reader Michael has made a cool-looking (if slightly morbid) web calculator to evaluate the Gompertz law prediction for different ages. If you want to know what the law implies for you in particular, and are not terribly handy with a calculator, then you might want to check it out.

Do you really need all those pills? Some researchers say dietary supplements help only those who need them, and don't make healthy people healthier.

“Don’t forget to take your vitamins?”

That healthful reminder from mom may soon become a thing of the past. While dietary supplements remain popular in the US, a continuous stream of studies are casting increasing doubt that the widely-accepted benefits are real. Researchers and regulators are taking notice, and some are beginning to deliver a different message.

Two studies published earlier this month are the most recent examples. One takes aim at vitamin E, the other at multivitamin supplements for women.

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) put to test the common “wisdom” that vitamin E lowers men’s risk for prostate cancer. A total of 35,533 men in the US, Canada, and Puerto Rico, received one of four treatments: vitamin E, selenium (an essential mineral thought to lower the risk of cancer when taken with vitamin E), both together, or a placebo. They found that taking vitamin E actually increased the risk for prostate cancer. Taken together with selenium, however, seemed to mitigate the increased risk that comes with taking vitamin E.

Bottom line, though, is that taking vitamin E or selenium – or both – did not reduce risk of prostate cancer.

The Iowa Women’s Health Study assessed the health affects of vitamins and minerals in over 38,000 older women. With a maximum follow up of about 20 years, the study showed that taking common vitamins and mineral supplements was actually associated with an increase in mortality rate, compared to women who did not take supplements.

We have to keep in mind, though, that studying the effects of vitamins and supplements is tricky. People don’t just eat them one at a time. The subjects in the SELECT trial took their vitamin E along with their normal diet. Other vitamins and minerals can interact with vitamin E in complex ways that researchers are far from understanding. So studies that try to parse out the effects of a single supplement have to be taken, pardon me for saying, with a grain of salt.

But while any single trial is not conclusive, a pattern emerges when one takes a broader view, according to Marion Nestle, New York University professor of nutrition, food studies, and public health. “The better the quality of research, the less benefit [supplements] show,” he told the Wall Street Journal. “It’s fair to say from the research that supplements don’t make healthy people healthier.”

There's nothing like the real thing.

Others agree. The Office of Dietary Supplements, part of the National Institutes of Health, says that while vitamin C has long been a popular remedy for the common cold, research shows that, for most people, vitamin C does not reduce the risk for getting a cold. On the other hand, taking too much vitamin C can cause diarrhea, nausea, and stomach cramps. And while taking vitamin B-6 and B-12 is commonly thought to reduce risk for cardiovascular disease, the data is not conclusive. In a 2006 statement, the American Heart Association said “evidence is inadequate to recommend…B vitamin supplements as a means to reduce cardiovascular disease risk.” There’s no disputing that calcium is important for bone health, but efforts to show it reduces the risk of cancer and heart disease have fallen short. And taking calcium supplements can increase risk for kidney stones.

Early studies suggested beta-carotene decreased risk for lung cancer. But two large studies published in 1994 and 1996 showed that smokers taking beta-carotene supplements were actually more likely to develop lung cancer than smokers who didn’t take the supplement. A follow up to the studies was performed in 2004. It concluded that beta-carotene was harmful to those at risk for lung cancer, even though the subjects hadn’t taken the supplement for years.

But that doesn’t mean all of us should stop taking our vitamins. For those with specific deficiencies or the malnourished, supplements are a necessary part of the diet. It’s recommended, for example, that pregnant women take folic acid. Folic acid is important for the kind of rapid cell growth that occurs during pregnancy. Taking it helps reduce the risk of birth defects.

Large studies that evaluate supplements, such as SELECT, are rare. In fact, many supplements remain untested, not only for their effectiveness, but for their safety as well. The FDA has a separate set of regulations for supplements than they do for drugs or “conventional” foods. According to these regulations, the “manufacturer is responsible for ensuring that a dietary supplement or ingredient is safe before it is marketed.” The FDA is responsible, however, for taking action if a supplement has adverse effects once people start taking them.

Sounds arse-backwards if you ask me. But no one’s asking me, and the fact is the supplement industry is big business. According to a National Health and Nutrition Examination Survey report published earlier this year, in 2006 about half of Americans were popping at least one supplement a month. In 2010 the supplement industry raked in $28 billion in sales, a 4.4 percent increase from 2009. Despite the growing number of studies that show a given supplement doesn’t work, people continue to take them.

Joseph Fortunato, chief executive of supplement retail giant GNC Corp., is quite okay with that. The Wall Street Journal quotes Fortunato from a company conference call transcript: “The thing you do with [reports of studies] is just ride them out, and literally we see no impact on our business.”

That may soon change if the National Center for Complementary and Alternative Medicine (part of the NIH) and other health institutes have their way. The growing body of data that consistently fails to show benefits has prompted them to push for more studies that explore how nutrients work – a body of knowledge that is surprisingly lacking.

So what do we do with all this uncertainty? If you’re considering taking a dietary supplement, get informed. Read up and talk to your doctor. But as professor Nestle says, it might be a waste of money for people without specific deficits. The best way to get the vitamins and minerals you need? The old fashioned way: a balanced diet.

[image credits: Johns Hopkins Bloomberg School of Public Health and Dietary Supplements For Health And Fitness]
image 1: pills
image 2: balanced

For those unfamiliar with her work, Sonia Arrison has been on the science beat for a decade, covering emerging technology for TechNewsWorld, their ramifications for Pacific Research Institute, and publishing two other books on modern tech issues. She’s also one of the associate founders of Singularity University, and presents there often. Here’s a quick overview of Arrison as it pertains to her new book on longevity – the SU class of 2011 makes an appearance around 2:00.

Here’s another promotional video, this one more focused on the technology discussed in 100+:

I’d start off by describing the technology that Arrison thinks will help humanity extend its lifespan, but you already know all about it. To regular readers of Singularity Hub, the first few chapters of 100+ will be more than familiar. Regenerative medicine based on stem cell treatments, genetic modification, and lab-grown organs – we talk about this all the time. Arrison puts it all together in a concise and compelling best hits list of modern science, attracting much needed attention to the successes we’ve already seen in repairing and replacing failed parts of people as they age or get injured. With straight forward prose and a palpable sense of enjoyment, Arrison steps you through all these advancements and lets you feel the awe of what we’ve already achieved.

That’s part of the purpose of the book. As Arrison told me, she crafted 100+ in order to “make it readable for the average Joe on the street.” She was inspired to explore the science of longevity after watching ‘extreme makeover’ type reality TV shows like The Swan. If people were crying in joy from having plastic surgery, how else might we want to change ourselves? From cosmetic augmentation to real transhumanism, Arrison realized that “the more [she] looked at it, the more it seemed like reality, not just science fiction.”

People want to be happier, healthier, and experience more life. That’s one of the fundamental arguments of 100+, and Arrison states her case strongly enough to convince almost anyone, and in a style that will be as accessible to your techno-phobic Uncle Walter as it is to your computer loving self. But if humanity wants more out of life, why haven’t we made more of a push for radical life extension? Partly, Arrison supposes, because we don’t realize regenerative medicine is so possible. “If everybody knew about it, we’d all put more energy into it and we’d all live longer, healthier, happier, lives.” To me, 100+ serves as a sort of evangelical text for those looking to spread the word about longevity.

Arrison, however, sees it a little differently: “some may call it ‘evangelical’ but I think of it as sort of a myth-busting book.” From the beginning, 100+ addresses the standard philosophical and pessimistic arguments against longevity. Bring up radical life extension with a large group and you’re bound to have someone posit that it’s natural to die, that we’re not made to live forever. Others will argue that humans have a negative impact on the environment, that aged people will bring down the economy, and that all rising populations are checked by disease and famine as Malthus surmised centuries ago. Well, “Malthus was wrong,” says Arrison, “because he didn’t account for human capital.” More people means more brains working on solving the world’s problems. And if longevity works the way she thinks it will, those minds will be have the vitality of youth, but with many decades of experience. 100+ spends a good deal of its literary real estate debunking the anxieties and barriers society throws up so it won’t have to seriously consider the consequences of humanity successfully living longer lives.

If disaster isn’t going to strike, what will? In what impresses me as the most daring, and yet most satisfying part of 100+, Arrison explores the impact 150 year lifespans will have on finance, family, and religion. People will have to plan on having money for decades longer, pushing us to be more responsible, more investment minded. Arrison thinks we’ll want to do more with that money because ultimately, “death limits our ambition.” Our families will transform to account for generations that span centuries and family trees whose branches split off in ways we don’t see today. With ovarian cell grafts, in vitro fertilization, and other emerging reproductive technologies women could have their own biological children at 80…100…even 120. Siblings could be born sixty years apart. The centers of our world will be radically different.

Arrison thinks religion will have to change with it. She originally thought ending the threat of natural death would kill religiosity. After all, why do we need an afterlife when we have endless life here and now? Yet to her surprise, Arrison’s research showed that religion doesn’t fade as people gain longer lives, that instead religions are adapting to focus more on the purpose of life. In her opinion, the religions that thrive will be those that help people find meaning and satisfaction with their extended time on this Earth.

While I’m much more of a nuts and bolts technophile, I found Arrison’s extrapolation of longevity’s impact on the social side of things very intriguing. True to its aim to be accessible to the masses, 100+ explores the impact on finance, family, and faith in a way that explains rather than condemns, and enlightens rather than proclaims. Without comprising her vision for the importance of life extension, Arrison still manages to be respectful of humanity’s more conservative elements. A bit of a tight-rope walk, but she pulls it off.

So there’s really little reason 100+ couldn’t be given to almost anyone in your extended social circle to get them thinking about the realities and possibilities of longevity. But what then? “Change has to come from the bottom up.” 100+ outlines the people, the institutions, and the trends we’ll need if we want to encourage life-extension science to be ready in our lifetimes. Arrison ends the book with a look at the movers and shakers that are actively pursuing immortality. Here her Silicon Vally insider credentials shine. Arrison also vents an often stated Bay Area frustration with the FDA, a bureaucracy that doesn’t even have an approval process in place for age-related treatments. To satisfy Arrison’s thirst for the fountain of youth we’ll need media outlets discussing longevity more regularly – “Instead of the healthcare crisis why aren’t we talking about making people healthier?” We’ll need philanthropists and governments to push for age-related research, and we’ll need everyone to make longevity a priority.

If 100+ is right about the escalation of longevity science in the next few decades, and I think it’s certainly likely we’ll have great advances there, then we could see the end to physical aging in our lifetimes. That’s something to marvel at. I asked Arrison what she would do with her extra time. Fitting for someone who confesses that she never feels like she has enough time, she gave many different answers. Family, traveling, charity, education… I bet many of our own lists would look similar. There’s so much for us to do with our time, and we haven’t even seen a fraction of what the future holds in store. 100 years ago, most people didn’t have indoor plumbing. Now we have the internet (a different series of tubes). Live to 150 and beyond and you’ll see things, you’ll be things, that you never imagined were possible. Sonia Arrison makes those possibilities seem within our grasp. All we have to do is accept our right to challenge death, and fund the science that could make it end. We’ve already had more successes than most of us know about. We could achieve much, much more.

[image credits: 100plusbook.com]
[video credits: Arrison Project]
[sources: Sonia Arrison, 100+]

One big happy. Unregulated fertility clinics have allowed the number of half-siblings – such as these three – to grow to groups as large as 150.

Imagine finding out you had a half-sister. You might want to contact her, find out where she lives, what she does for a living, and whether or not she likes sushi.

Now multiply that by 150.

At the same time that artificial insemination is a miracle for so many couples who can’t conceive children, it’s also an example of how slack regulation can lead to unhealthy consequences. The New York Times recently reported that a single sperm donor has fathered 150 children, and his fertile seeds of life are still being used to impregnate more women still.

The Waltons would have needed the show’s entire hour to say goodnight.

This particular cohort is one of the largest to be found on the Web-based registry that tracks children born from specific donor numbers – donor identities are kept anonymous. But more and more there are groups of 50 or more half-siblings.

Cynthia Daily, who’s child is among the group of 150 siblings, told the New York Times, “It’s wild when we see them all together – they all look alike.”

Not only is this strange, it’s worrisome.

What if, for example, the donor had a genetic defect that he’s unwittingly – or worse, wittingly – passing on to all of these children? Logically one might think that fertility clinics would disqualify someone who had, for example, a genetic heart defect. But fertility clinics aren’t thinking logically, they’re thinking with their…um…test tubes. The FDA requires that donors in the US are tested for “communicable disease agents and diseases.” Screening includes a medical history interview and tests for infectious diseases such as hepatitis and HIV.

How effective is the screening? Just ask Tyler Blackwell. Curious about his biological father, Tyler and his mother located him and sent him a letter suggesting they might meet. They got no response. Later, the donor’s sister contacted Tyler and his mother – not to help Tyler meet his father, but to tell him there was a good chance that he had a genetic heart defect. Tyler’s biological father had almost died at the age of 43 when his aorta ruptured. Two of the man’s brothers have the disorder, as well as his mother. And by the way, the family has a history of a connective tissue disorder called Marfan’s syndrome. Tyler’s biological father had never told the three clinics at which he donated sperm of his genetic conditions. His sperm has been used to father at least 24 children, yet he was never required to update his medical history with the clinics.

Three half-siblings pictured with their mothers.

“It didn’t occur to anyone to tell us.”
A much more egregious example recently occurred in the Netherlands. A man with Asperger’s Syndrome, a mild form of autism that affects a person’s ability to socialize and communicate effectively with others, was able to donate sperm by lying to a clinic. After telling the clinic that he was perfectly healthy, his sperm was used for 18 months to father at least 22 children. Some of the children are already showing signs of autism. The man had also been previously treated for depression, which is also thought to have a strong genetic component. Inexplicably, the man is still at large and he’s still finding women who will use his sperm for artificial insemination or even by having intercourse with him.

The above examples illustrate the need for better monitoring and more comprehensive regulations. The US has been slow to adopt regulations. While Britain, France, Sweden, and other countries set limits to how many children a single donor can father, no such limit exists in the US. “We have more rules that go into place when you buy a used car than when you buy sperm,” Debora L. Spar, president of Barnard College and author of “The Baby Business: How Money, Science and Politics Drive the Commerce of Conception” told the New York Times.

Because there is no formal registry from which donor offspring can get information or make connections, a Donor Sibling Registry was created by and for the donor-conceived community. Half-siblings that share a mutual desire to make a connection can find each other through the registry. The registry can also potentially be a lifesaver by connecting offspring with their donors, thus giving them access to medical information that fertility clinics can’t be bothered to collect. “There are no rules or regulations about donor identification, testing donors, monitoring numbers of children or medical records.” Wendy Kramer, co-founder of the registry told ABC News. “No one is watching. There are no laws. They don’t keep track.”

Genetic diseases aside, how wise is it to alter the gene pool so rapidly and disproportionately as when fathering 150 children or more? Rare diseases could spread, and then there’s the increased likelihood of accidental incest. As a mother of a donor-conceived teenager told the New York Times, “My daughter knows her donor’s number for this very reason. She’s been in school with numerous kids who were born through donors. She’s had crushes on boys who are donor children.”

Given the industry’s lack of regulation, it’s not surprising that we don’t really know how many children from sperm donors are born per year in the US. Estimates range from 30,000 to 60,000. Although sperm banks ask mothers of donor children to report when a child is born, only about 20 to 40 percent of mothers do.

When Louise Brown became the first baby born using in vitro fertilization back in 1978, the British government charged a committee with the task of recommending regulations for what was sure to become a big international industry. What they produced was called the Warnock Report, named after the philosopher who led the group. The report recommended limiting the number of children a donor father could have to 10. The New York Times points out that “the regulations have become a model for industry practices in other countries.”

Obviously, the US is not one of them.

[image credits: CBC and MSNBC]
image 1: children
image 2: with mothers

A substance extracted from pigs has allowed Marine Corporal Isaias Hernandez to regain much of the muscle he lost to a mortar explosion while serving in Afghanistan.

It was only a year ago that ACell’s “miracle powder” was sprinkled on amputated fingers and shown to stimulate the regeneration of fingertips. The world was both awed and skeptical of the powder’s regenerative power, touting that it would revolutionize regenerative medicine or calling it was quack science.

A fingertip is one thing. A thigh, quite another.

After losing most of his thigh muscle in a battlefield explosion, one marine was given a second chance when another such miracle powder caused much of his thigh to grow back. It’s not only a wonderful feel-good story, but demonstrating that the same substance can grow back different tissues suggests that we may have only seen a small part of its full regenerative potential.

October 12, 2004, Afghanistan

At the time the mortar exploded, U.S. Marine Corporal Isaias Hernandez and his companion were working to repair a truck. If he hadn’t been carrying a television at that moment he, like his companion, would have been killed. The TV absorbed most of the shrapnel, but what it missed tore through Hernandez’s arms and legs. His right thigh got the worst of it: 70 percent of its muscle was sheered off and the femur was fractured. For the next four years the Corporal underwent multiple surgeries and constant physical therapy, but his leg wasn’t getting stronger. His only option was amputation, as is the fate of the vast majority of limbs with severe muscle damage.

Enter Dr. Stephen Badylak, Director of Tissue Engineering at the University of Pittsburg’s McGowan Institute for Regenerative Medicine. Dr. Badylak and colleagues offered Corporal Hernandez an alternative to amputation: regrow the muscle. The key to this seemingly miraculous procedure is a material obtained from pig bladders. As the material’s name, the extracellular matrix implies, it is the mix of chemicals that fills the space surrounding the body’s cells. It’s a complex mixture of hormones, structural proteins, and other molecules that maintain the health and function of the cells, as well as mediates cell-to-cell communication. It also guides tissue growth. Following an intense physical therapy program to strengthen the 30 percent of muscle he had left, doctors made an incision deep into Hernandez’s thigh and applied the extracellular matrix. Instead of a powder like ACell’s, Dr. Badylak’s group turned the material into a gel form. “You can’t use a powder to replace a tendon,” remarked Dr. Badylak. It went to work, spurring not only the growth of muscle tissue but tendons, as he mentioned, and the proper vasculature as well. About six weeks after the surgery the Marine began to feel his strength returning. What’s more, he saw muscle bulking up in the area that the extracellular matrix had been applied. “I used to have a hard time walking and going up and down stairs,” he told Purdue alumnus magazine in a feature story on star alum Dr. Badylak. “I can pretty much walk and do stairs fine now.”

After more than a decade since Dr. Badylak first treated a patient with the extracellular matrix material he still doesn’t quite know how it does what it does. A few things researchers do know: the extracellular matrix becomes part of the tissue it is placed into; as part of the tissue it can grow and heal; it somehow recruits the body’s own stem cells to its location; and it changes the body’s immune response from attacking to “constructive remodeling.”

The decision to use extracellular matrix from pig bladders was not a scientific one, but an economic one. Pig parts were in abundance in butcher-happy Indiana near Purdue University where Dr. Badylak first began the research.

Pig extracellular matrix does more than just regrow thigh muscle. ACell's remarkable MatriStem powder has been used to regrow fingers.

The fact that the extracellular matrix recruits the body’s own stem cells is huge because it obviates the need to introduce stem cells from an outside source. As we’ve discussed before, even genetically-identical cells derived from the patient can be problematic. Reprogramming skin cells, for instance, into heart cells requires significant molecular manipulation, and these manipulations can lead to side effects such as rejection or cancer. The fact that the extracellular matrix puts the body’s own stem cells to work is simpler and safer. It may also get Dr. Badylak’s treatment into clinics sooner. “It…simplifies treatment because it’s much easier to get FDA approval with stem cell research when you don’t have to harvest them,” he told Purdue alumnus.

As Dr. Badylak and his colleagues know, every little bit helps. Their ‘MiracleGro For Muscles’ wasn’t always seen as such. Even after years of watching the extracellular matrix successfully morph into whatever tissue it was inserted into–from nerve cells to muscle and bone–the research stubbornly refused to get funded. As Dr. Badylak told the Purdue alumnus, “Nobody thought it was worth funding because it was such a crazy idea. Why would anyone want to put pig tissue in a human?” But profit-minded entrepreneurialism saved the day from pundit-advised conservatism. Eli Lilly and Co. and DuPuy, an orthopedic company in Indiana, put real money into the idea. With the help of drug company coffers Dr. Badylak’s research took off and eventually Washington came aboard. The current study that gave Corporal Hernandez much of his thigh back is a trial in collaboration with the U.S. government. As part of a $70 million government program for regenerative medicine, it’s hoped that Hernandez’s will be the first of many such success stories.

Given that the U.S. is currently fighting two wars, the victory for regenerative medicine couldn’t have come at a better time. “I get six to eight emails a day (from potential patients),” Dr. Badylak said in December of last year, long before news of Corporal Hernandez’s regrown thigh. Let’s hope that this treatment makes it to the clinic soon, so that Dr. Badylak can answer not only their emails, but their prayers as well.

[image credits: dailymail.co.uk, Acell]
image 1: Hernandez
image 2: Acell

Behold: the Cornucopia of Youth?

When lunchtime rolls around, what are you thinking about: your health or your hunger? We all want to eat healthier in theory, but for many of us, attempts at healthier diets tend to be sporadic and short lived. Which is unfortunate on the one hand, since reams of medical research is showing that eating “right” has a probabilistic effect on health — and lifespan! On a demographic level and in controlled individual trials, people who eat better can live decades longer in excellent health.  Meanwhile, the rest of us are getting by on whatever diet we’ve lucked into and relying on doctors to do the rest.  But how long will we have to wait before researchers develop bio-technologies that will halt or even repair the damage caused to your body by aging? Are we doing enough in the mean time?

If it were up to David Murdock, he’d tell you to be doing more. A billionaire several times over, Murdock has lived the American dream, starting out destitute and penniless after World War II and later rising to prominence and fortune through business. But losing both his wife and mother to cancer several years ago radically altered his priorities and made him a man on a mission. Now he’s investing his time and money to improve the state of health, biotechnology, and personal longevity… including his own. (He plans to live to 125!). His message: No matter what you pack for lunch there’s likely lots of room for improvement — and he’s not afraid to tell you so. He’s been featured on the Hub before, along with others of his cohort who believe the key to longevity is eating right and exercising.  Average lifespan (and health-span) are correlated with lifestyle and diet is a big component of that.  Individual supplements are touted as essential for anyone who wants to improve their chances of ultra-longevity – Ray Kurzweil famously takes over a hundred on a daily basis.  And some people take this ethos to heart, devoting a huge portion of their lives to optimizing their meals and exercising so they can spend even longer doing it.

But there are reasons to be skeptical of claims like these too.  Sure, Murdock enjoys enviable health and he’s in his late eighties.  But he didn’t start his extreme healthful habits until his sixties and has always been “naturally slender”: if he’d been predisposed to accumulate damage from eating his choice of less-saintly foods, it would have built up by the time he began his crusade.  His wife Gabriele’s cancer killed her when she was 43: she wasn’t lucky enough to last until he learned the nutritional secrets he believes could have saved her.

Billionaire David Murdock intends to live to 125

Meanwhile, others who have lived long past their 100th birthdays such as Sakhan Dosova (who may have been as old as 130 when she died) rarely list their favorite foods as carrots or cantaloupe. Her favorite food: cottage cheese and ground wheat.  We wouldn’t have heard about her, or her predilection for dairy and carbs, if she hadn’t gotten to such an impressive age – but by the same token, we would never have heard of someone like Murdock who used the same diet and wasn’t doing as well.  Why attribute health to diet, and not good genes, or any of the other predictors of low mortality? Murdock also has the advantage of being a billionaire: that helps.

Let’s optimistically assume that Murdock and other who overhaul their lives to extend them are doing something right, and will get more years for their trouble.  Even so, some people don’t want to settle for lifestyle-based methods and the – at best – a few extra decades of extended life.  SENS has been working on regenerative medicine, which is intended to remove cumulative harm done to the body using bio-technology that we can use to possibly repair damage.  If it works as advertised, it doesn’t have the upper bound of efficacy that lifestyle-based choices seem to have: you could keep patching yourself up until you were several centuries old, not just the one and a quarter Murdock plans for.

However, research in general progresses slowly, and you can’t yet check in to a rejuvenation pod and emerge looking twenty-something every time you have another birthday.  As long as there’s a hint that passing on the bacon and filling up on blueberries will help, take advantage: they might let you live long enough to see the really snazzy tech.

[image credit: Jemal Countess/Getty Images]

Eye Robot

Robots have been trying to invade our bodies for years. Now they’ve found a way to get in our eyes and–if we’re lucky–we won’t even know about it.

Bradley Nelson is a Professor of Robotics and Intelligent Systems at ETH-Zürich and is the founder of the Institute of Robotics and Intelligent Systems where he leads the Multi-Scale Robotics Lab. Dr. Nelson and his team have created a robot that, once injected into the eye, can be moved forwards, backwards, and turned in place–all by remote control. If they can shrink their micrometer-scale robot enough to fit into a 23 gauge needle it could be injected into the eye with little or no anesthetic.

The MagMite, as it’s called, is driven by magnetic propulsion. At the center of 8 overlapping magnetic fields (and their magnets) the MagMite’s movements are the net result of changes in the strengths of the magnetic fields. It has a mass of 30-50 µg and, measuring 300 µm x 300 µm x 70 µm, the microbot (a nanobot, of course, would have dimensions in the hundreds of nanometers) is comparable in size to the blood vessels in the human retina having diameters of approximately 150 µm. This is important as Dr. Nelson hopes MagMite will one day be used to treat retinal vein occlusion, a common cause of glaucoma or macular edema. The spatial resolution afforded by the MagMite would allow physicians to deliver drugs in a precise, site-specific manner. People with age-related macular degeneration, the most common cause of blindness among older people, would also benefit. Age-related macular degeneration is often treated with injections directly into the eye. But this leads to rapid diffusion of the drug and the need for regular injections. MagMite could remain in the eye for months, dispensing the drug in a time-release fashion.

So far it’s only been tested in synthetic eyes or eyes dissected from animals (the demonstration in the clip below is in a pig eye). Plans are in the works for human trials. Any takers? Try not to look at the needle headed right for your eye. Remember, it probably won’t hurt.

The magnetic control system developed by Dr. Nelson’s group is a major improvement over robotic propulsions systems of the past. A common strategy for designing medical robots has been to give it a kind of motor with the idea of enabling them to swim their way to targets in the body such as a tumor where they could deliver local chemotherapy. As we’ve pointed out before these mechanical approaches have several drawbacks including tissue damage caused by moving parts and the possibility of the motor getting snagged. These robots would also require nano-sized batteries which simply don’t exist yet. The ideal situation would be a robot that doesn’t require internal propulsion or power. That’s what Dr. Nelson has in his MagMites. We can conceive of letting them course through the bloodstream, passively going with the flow, until they near their target where the magnets could then be turned on and guide it the rest of the way.

The MagMite is a major achievement, but there are some additional major advances that need to be developed before anything like the scenario I described above becomes a reality. For one, the robot has to be seen. Dr. Nelson’s group chose to develop their MagMite in the eye because they can watch it from the outside-in (I’m certain it was experimental feasibility rather than a desire to treat eye conditions that drove their test target–but I digress). But even the eye presented difficulties. The various types of tissues that make up the eye scatter light differently. It was a major challenge for the team to tweak the optics so they could properly monitor the MagMite’s movements. Good luck trying to reach that lung tumor. For that to happen, the MagMite technology will probably have to be merged with that of carbon nanotube transmitters that would transmit the robot’s precise location. Again, this technology is a ways off yet.

Dr. Bradley Nelson's remotely-controlled MagMite may pave the way to future nanotechnology-based medicine.

But Dr. Nelson’s proof of principle is indeed a beautiful display of technological finesse. To manipulate 8 magnetic fields with such a soft touch as to precisely control a micrometer-sized robot is mastery. The MagMite’s speed tops out at 12.5 mm/s or 42 times the robot’s body length per second. At such speeds the robot can produce enough force to push objects of comparable size. It’s easy to get excited about the prospects of using MagMites for noninvasive surgery, at least in the eye where small changes in structure lead to big changes in vision. And the magnetic power required to move it is 2 mT, about 50 times the average magnetic field of the Earth and a thousand times less power than a typical MRI magnet.

At this point, the MagMite is really just a small magnet, not much of a robot at all. But that’ll change soon when Dr. Nelson enables it with drug delivery capabilities. At hundreds of microns the MagMite is not the ideal vehicle for drug delivery. Nanobots, with dimensions in the hundreds of nanometers, would be able to go where MagMite cannot (nanoparticles small enough to pass through cell membranes are already being created in labs). The dream application, of course, is to unleash trillions of robots into the body that would deliver drugs to specific sites, including specific organelles inside of cells. And yes, again, this technology is quite a ways off. But with Dr. Nelson’s demonstration, it was brought that much closer.

[image credits: NewScientist, Institute of Robotics and Intelligent Systems]
[video credit: NewScientist via youtube]

image: Bradley Nelson
video: NewScientist

If asking nicely doesn't work, maybe science can reveal the secrets of the immortal jellyfish!

The search for the fountain of youth has been ongoing ever since man decided that dying wasn’t all that appealing. And now, it appears that this elusive holy grail has been found, albeit by a species that is not ours! So who is the lucky winner of the everlasting life sweepstakes? None other than the humble and dime-sized jellyfish known as Turritopsis nutricula. This creature has accomplished what no other biological being on our planet has ever been known to do: reverse it’s aging to become young again after reaching full maturity! As early as 1992, scientists had observed this phenomenon in Turritopsis and research into its secrets was ongoing. However, a recent spike in the numbers and geographic distribution of this species has once again brought it to the attention of the greater scientific community because of the many important breakthroughs we have witnessed in stem cell research in the past decade. As regenerative medicine continues to grow into the future of medicine, it’s clear that this tiny jellyfish may hold the answers to not only addressing the many aging-related ailments we face, but also our own mortality!

In the picture below, you can see the typical lifecycle of a jellyfish. It starts out as a larva that eventually sinks to the bottom of the ocean and attaches to a sturdy substrate and continues development into a polyp that resembles a sea plant. The polyp then matures to become a free-floating medusa, what we commonly recognize as jellyfish resembling an upside down saucer with tentacles. Not much excitement so far, but Turritopsis has put an interesting twist to this process. It undergoes development much like what I’ve described above and what many of its relatives go through. However, during times of stress like a shortage of food, Turritopsis responds by beginning to reverse the process before eventually becoming a polyp again. From this point then, it can again develop into a sexually mature medusa when conditions become more favorable. Theoretically, it can repeat this process indefinitely as its cells undergo a process called transdifferentiation, a rare biological process whereby any non-stem cell can become a different cell entirely. It is still unclear whether only specific cells can only become other specific cells or if any cell in Turritopsis has the potential to become any other cell.

The typical lifecycle of a jellyfish. Exciting, isn't it?

Ok, what Turritopsis does is admittedly cool, but why would we care? As you know, here at the Hub, one of our favorite topics are stem cells and all the promise they hold for regenerating tissue and treating a vast array of ailments. And while stem cells are one avenue to reach the goal of regenerating damaged or diseased tissues, transdifferentiation is another option that can get us to that goal.

Allow me to digress here and clarify the difference between these two systems (also see the below figure). Stem cells are cells that can differentiate into any type of cell. They can be isolated from a natural state i.e. embryonic stem cells (ESCs), or created by taking already differentiated cells and coaxing them to undifferentiate into stem cells, becoming induced pluripotent stem cells (iPSCs). These stem cells can then differentiate into another type of cell. On the other hand, transdifferentiation doesn’t require the middle step of becoming a stem cell. Any differentiated cell can become any other differentiated cell, given of course that it receives the correct signals.

If transdifferentiation can be harnessed in the lab, we may be able to avoid using stem cells altogether.

Much of the advances in stem cell technology have come from having an understanding of how stem cells naturally develop into different cell types. Thus, nature’s methods are teaching us how to manipulate stem cells and turn them into the desired cell type. And when it comes to transdifferentiation, the hope is that we will eventually be able to learn how creatures like Turritopsis skip the stem cell step and go directly from one cell type to another. As such, a recent breakthrough in using transdifferentiation for therapeutic purposes was reached in the laboratory of Dr. Deepak Srivastava of the Gladstone Institute of Cardiovascular Disease at the University of California, San Francisco. In a recent article in the journal Cell, Dr. Srivastava’s group describes their success in getting architectural cells in the heart called fibroblasts to differentiate into cardiomyocyte-like cells. In case you’re rusty on your cardiac anatomy, cardiomyocytes are the cells in the heart that contract and result in it’s rhythmic beating. And as Dr. Srivastava explains in the video below, it is the loss of these cells and the development of scar tissue that is debilitating to those fortunate enough to survive a heart attack. So by just switching on three genes in the fibroblasts, the researchers were able to coax them to transdifferentiate into cardiomyocyte-like cells that looked and behaved like cardiomyocytes. Taking it one step further, they implanted these cells into the hearts of mice and found that they behaved just as one would expect them to. In a previous post, we had described similar results, but in that work, the researchers had to first produce stem cells from skin cells before producing the cardiomyocytes. Clearly, Dr. Srivastava’s group has taken this to another level.

So while we still have some hurdles to overcome before this type of treatment is available for use in humans, it is indeed on its way. The amazing work being done in laboratories such as Dr. Srivastava’s are inching us closer to the day when perhaps we’ll be able to not only treat various ailments, but also to turn back the hands of time and reverse our aging like Turritopsis has been able to do. A recent press release by Advanced Cell Technology (ACT) hints at some potentially new technologies they are developing to take advantage of transdifferentiation. While most of their work thus far has focused on stem cell-based treatments, it’s encouraging to see companies like ACT put time and money into exploring transdifferentiation-based treatments as well. Sure everyone is working to get to the same goal, but there may be more than one way to get there!

[Sources: Cell, National Geographic, Wikipedia, Advanced Cell Technology, Gladstone Institute of Cardiovascular Disease, Nature Reviews Genetics, KQED TV]
[Image Credits: Russel McAvoy, Nature Reviews Genetics]
[Video Credit: KQED TV]

Patients can control a computer with their thoughts using ECoG electrodes placed directly on the brain.

A temporary surgical implant enabled patients to “talk” to a computer. Just by thinking the words aloud in their head they were able to control a cursor on a computer screen. The brain-computer interface (BCI) technology could one day be used to help people who are unable to talk or have other physical disabilities due to brain injury. The technology could one day be used to read a person’s mind.

Published April 7 in the Journal of Neuroengineering, the study was carried out by scientists at the Center for Innovation in Neurosciences and Technology at Washington University in St. Louis. The team was led by Dr. Eric Leuthardt, a pioneer in the field who previously developed a BCI that enabled people to play video games with their thoughts. In the current study a net of ECoG (electrocorticographic) electrodes was temporarily placed beneath the dura, a layer of connective tissue surrounding the brain. Rather than performing a craniotomy and placing electrodes on the brain for an experiment–might be hard to get approval for that–the original purpose of the electrodes was to map activity in patients with intractable epilepsy so that those areas could be surgically removed. As human brain studies are often brought about, Dr. Leuthardt combined his clinical aims with experimental. The ECoG electrodes detect the activity of underlying neurons and transmit the signals to a computer that then uses the signals to perform a task. In the current study the patients’ brain activity was used to control a cursor on a computer screen. Remarkably, the patients were able to accurately control the cursor in as little as 4 minutes. The slowest of them took 15 minutes. The ease with which the patents were able to perform the task is an encouraging sign that the technology could be applied to prosthetics control.

Other researchers have successfully used a BCI to interact with a computer. What’s novel about Leuthardt’s study was the region of the brain they recorded from. Building off work in monkeys where a mathematical relationship was found between the activity of motor cortex neurons and movements produced, early work in neural interfaces for prosthetic control logically focused efforts of how to use the motor cortex as the brain activity source. Leuthardt’s group, however, took a different approach. They hypothesized that, instead of imagining an arm movement–from right to left, for example–the patient could control the cursor with sounds either spoken aloud or imagined.

Instead of recording from the motor cortex, the researchers needed to record from the speech centers of the brain: Wernicke’s area in the temporal lobe and Broca’s area in the frontal lobe. The patients were asked to say or think of four sounds: oo, ah, ee, and eh. The computer then associated the patterns of brain activity that represented each of the sounds and tied specific cursor movements to the sounds. When the patient said or thought “ah” for example, the cursor would move left.

Spoken or imaginary sounds generate brain waves which are recorded by ECoG electrodes and sent to a computer to control the movements of a cursor.

Using the brain’s speech centers instead of the motor area was a major achievement. Human speech has been studied extensively with brain imaging techniques such as positron emission tomography (PET) or functional magnetic resonance imaging (fMRI). Data from these experiments have revealed a great deal about how different parts of the speech network work together to produce and understand language. But prior to Leuthardt’s demonstration it was not known if speech network activity could be used in BCI control.

Will the computer understand us if we simply talk to it? This is important for neuroprosthetic devices of the future as it expands the repertoire of brain function that clinicians can potentially use to control a robotic limb.

Another way to phrase the above question: can the computer read our minds? Amazingly, the answer seems to be yes. But simple oos and ahs are one thing, articulated thoughts are quite another. When we talk–either to each other or internally to ourselves–our thoughts aren’t limited to the words we’re using. Our brain relates to the words in intuitive ways, as in all of the imagery and associations that pop up in our heads when we hear a simple word like “ninja.” BCIs are a long way off from extracting the tremendously more complex idea of ninja our brain conjures up, but understanding overt statements from the brain is a step in that direction. It’s fun to think that this technology might be used someday to record our thoughts in the same way tape recorders are used. Brain implants could enable us to “jot down” lecture notes in our thoughts and retrieve them from the computer later. You’ll definitely want to keep those notes heavily guarded, lest someone hacks in and realizes that your mind kept wandering to the cute girl in the row next to you.

The video below from Russia TV Today is a great summary of the state of BCI technology today. Instead of using surgically-implanted ECoG electrodes, the Russian scientists in the video use a much more user-friendly “shower cap” of EEG electrodes that can read brain waves from outside the head. The video nicely illustrates the technology, including the difficulties of calibrating BCIs. Check it out as users solve puzzles, drive a remote controlled car, and move a ball across the floor using only their thoughts.

Computers are already being used to read our minds–and companies are cashing in on the data. Neuromarketing is a field born when a neuroscientist performed the Pepsi Challenge while scanning people’s brain activity with fMRI. The study showed that a part of the brain called the medial prefrontal cortex lights up when people really like a product. As before, Pepsi beat Coke and when they drank Pepsi the MPC lit up. But then why, if more people prefer Pepsi, does Coke dominate the market? The answer came when researchers uncovered the labels. Now that the people knew what they were drinking, the MPC lit up with Coke, not Pepsi. The conclusion was that Coke’s advertising was much more effective than Pepsi’s: even though people preferred Pepsi, they thought they preferred Coke. Lighting up the MPC meant a refreshed and satisfied Coke drinker. Thus, a cottage industry was born. Companies began putting people in MRI machines and testing their slogans and ad campaigns, and watching to see if the MPC lit up. If it did, it meant the consumer was thinking, “I need that pair of shoes.”

The potential of combining mind and machine is limitless. The two are being brought ever closer as developments in BCI technology proceed in parallel with our increasing understanding of the how the brain works. The future of BCIs will take us in even more exciting and unpredictable directions. Whether it improves the lives of disabled people, enhances our use of information, makes video games more fun, or makes companies money only time will tell. Eventually, I have no doubt, it will be all of the above and more.

[image credits: Journal of Neuroengineering]
[video credit: moscowbci via youtube]

video: Russia TV Today