When my mother was diagnosed with breast cancer, she surmised, “Hell, something’s gotta kill you.” Well, maybe not. Researchers are working diligently to address the seemingly unavoidable realities of aging and dying. In fact, the University of Southern California founded the Davis School of Gerontology for such a purpose, and the institute serves as the oldest and largest institute of its kind. Establishing the school was a groundbreaking, visionary achievement. When it was founded in 1974, less than 10% of the US population was 65 and older, the baby boomers were still young, and geriatric issues were barely in the national consciousness. Undoubtedly, the founders foresaw a dramatic shift in the age distribution in the coming decades, and now it’s projected that 20% of the population will be over 65 and older by 2020. With this same spirit of innovation and foresight, Davis faculty members continue to be on the cutting edge of gerontological science. The school also strives to translate its discoveries into programs that help the community deal with medical, psychological, and social effects of aging. At the dawn of a major change in age structure in the US, high impact research and outreach programs like the ones at the Davis School of Gerontology will become increasingly important.
Scientists worldwide are trying to clear what I call the second hurdle of longevity. The first hurdle was cleared in the industrialized world with the advent of antibiotics, vaccines, and improved sanitation, which led to a punctuated increase in life expectancy. Fortunately, even less developed countries are catching up, a fact beautifully demonstrated by Hans Rosling’s presentation in BBC Four’s The Joy of Stats documentary. However, as people are living longer, we have hit the second hurdle. People are developing cancer, Alzheimer’s, and other disorders influenced by age that cut life short and diminish its quality. Some are even saying that the one year increase in life expectancy seen every four years for the past two centuries may be reaching an upper limit. Recent CDC reports on 2008 data show that life expectancy in the United States decreased by over a month that year.
Faculty at the Davis School of Gerontology have adopted a multi-pronged approach to the problem and are pursuing various avenues that may lead to a solution. Caleb “Tuck” Finch and his colleagues have been investigating the interaction between inflammation and the aging process. He posits that postnatal factors such as environmental pollution and diet may exert aging effects through inflammation pathways. He also investigates the role hormones may have on the aging process, observing how changes in sex hormones late in life could mediate neural senescence. Generally, he is optimistic about treating the neurodegenerative diseases of aging, believing we’ll be able to lower the risk of Alzheimer’s and control its course by the next decade (you can find an in-depth interview with Dr. Finch here). Of course, even if we mitigate the risk factors and slow the progression of the disease, Alzheimer’s will be a persisting concern for the elderly and the final outcome will be unavoidable for those who develop it. Also, there are many manifestations of dementia, most likely with distinct or diverging etiologies. Even if we prevent the buildup of amyloid plaques, reduce inflammation, and protect cholinergic neurons, my grandpa will still forget where he put the remote.
Another faculty member, Dr. Valter Longo, extended the lifespan of yeast 10 times. If there were a yeast category for the Methuselah Foundation’s Mprize (an award given to scientists who significantly increase the lifespan of mice), Dr. Longo would have won handily. In both yeast and mice, a surefire way to enhance longevity is through caloric restriction (CR), which is essentially a state of persistent hunger. On its own, CR can produce a 3-fold and 30-50% lifespan increase in yeast and mice, respectively. Currently, CR has yet to provide any definitive results in primates, but some circles aren’t waiting for the science to unravel and and actively promote the CR diet as a means of human life extension. I know people who have jumped on the bandwagon and willfully sustain mild hunger throughout the day. Perhaps I’m weak-willed, but I could not bear the torment of knowing I could never be fully satiated. Fortunately, Woody Allen’s wisdom provides a rationale for my abstinence from food abstinence: “You can live to be a hundred, if you give up all the things that make you want to live to be a hundred.” Also, there’s evidence CR can lead to a weakened immune system.
Fortunately, Dr. Longo has helped identify the downstream molecular targets of CR, so with appropriate drugs and genetic manipulation, food abstinence may not be necessary. In fact, it was the genetic down-regulation of nutrient sensing pathways that enabled Longo and his team to decuple the yeast life span. Will we see these findings converted to therapies for humans? It’s exciting to know that the molecular cascades that were altered in yeast have human correlates, and a polymorphism in the gene of a transcription factor along this pathway may confer a longer lifespan. While genotyping may reveal your allelic configuration, gene therapy is still on the shelf and drug candidates/targets have not yet been identified. Also, there may be unforeseen, deleterious side effects caused by nutrient sensing inhibition in humans. For the moment, it seems uber-aged yeast may have applications in beer production sooner than human longevity.
It’s almost certain that we’ll live longer in the future. But with the diminished quality of life associated with old age, will anybody want to? I’m reminded of my grandfather, who has to struggle with every step and is often frustrated when he forgets things. He often says, “Jeremy, getting’ old isn’t for sissies. If you’re a sissy, don’t get old.” This sentiment reflects the findings of USC faculty member Eileen Crimmins and her team, who reported that a decrease in morbidity is not co-occurring with the increase in life expectancy. In other words, people can expect to live longer, but they can also expect to spend more years in a deteriorating state. This was primarily linked to second hurdle issues (diabetes, cancer, heart disease, and stroke) as well as accidents leading to loss of functioning. Most strikingly, in the past decade there has been an increased prevalence of mobility disability in all age groups, even for those aged 20-29. It’s clear that without effective rejuvenation-targeted interventions, longevity therapies of the future will be disappointing. In the mean time, we must adhere to that tired mantra: “eat right and exercise.”
From the perspective of a non-scientist, playing with inflammation pathways, yeast, and public health statistics may seem trivial. What do caloric restriction studies in mice mean to you if you're dealing with an aging parent who can barely stay on the road? How can gene knockout experiments in yeast keep your grandfather from falling when getting out of the bathtub? It's refreshing to see that the school does not shy away from these issues and has spearheaded fall prevention, autobiography writing, and caregiver support initiatives. This service component of the school is a positive model for both scientists and futurists. While it is important to tackle the big questions of longevity and rejuvenation, we must not forget the basic needs of the elderly living with us today. The Davis School of Gerontology demonstrates that it’s possible to have your head in the clouds and your feet on the ground at the same time.
Dr. Gerald Davison, the dean of the school, commented on the importance of the community outreach.
We are committed to serving the community in ways that take advantage of our scientific expertise. As a university, USC has a long tradition of doing this and, as a professional school within the University, we are especially attuned to the responsibilities of trying to improve the lives of our neighbors.
Dr. Davison also described how the school blends their research and outreach.
Our services are evidence-based, and our research is either applied or else basic with applied implications. For example, our research-based understanding of Alzheimer’s disease informs the outreach we do to the caregivers of Alzheimer’s patients.
This seamless integration of innovative research and clinical application represents a triumph of translational medicine. It facilitates the transition of discoveries from the lab bench to bedside and may hasten the day that the specters of aging are a thing of the past.
Through conventional treatment, my mother was able to beat the cancer. For the moment, she has avoided death, and she cherishes every moment of every day. Occasionally, she restates the ominous warning, “Something’s gotta kill you.” There are few things I revel in more than proving my mom wrong, and perhaps one day aging researchers at USC and beyond will do just that. I’m hoping that we can clear the second hurdle.
[image credit: USC (modified)]
[sources: USC, LA Times, CR Society, Understanding Uncertainty, The Science Network, The Guardian]