Fight Aging!

S. Jay Olshansky is one of the researchers behind the Longevity Dividend initiative, a long-standing and fairly conservative academic initiative aimed at producing far greater funding for research to slow aging. It is one of a number of groups attempting to change the present academic and public research edifice from the inside. Olshansky recently issued a call to action, arguing for the research community to focus on increased healthspan rather than increased lifespan. From my perspective he makes this argument for all the wrong reasons, based on an expectation that it will prove impossible to produce large gains, say two decades or more, in either life span or health span in our lifetimes. This is actually a fairly common viewpoint among researchers, many of whom believe (a) that the only viable way forward is through incremental alteration of the processes of metabolism in later life, an enormously slow and expensive proposition with a limited potential to produce benefits, or (b) that biology is too complex for the existence of any simple strategy to produce sizable improvements in life span.

For my part, I'm not sure that it much matters whether the focus is on healthy lifespan or overall lifespan, as a comparatively simple strategy that should produce large gains in life span does in fact exist, and is described in detail in the SENS rejuvenation research proposals. The strategy is to identify and repair the known forms of cell and tissue damage that cause aging, that arise as a side-effect of the normal operation of metabolism and have no deeper cause themselves. The best analogy is rust in a complex metal structure; rust is very simple, but the progression of decay as the structure falls apart will be as complicated as its shape. Aging has simple causes, it is exactly an accumulation of damage, but it appears complex in its progression because cellular biology and its reactions to damage are complex.

Since aging and age-related ill health have the same cause, are in fact the same phenomenon, it is the case that repair is the best approach whether targeting either healthspan or lifespan. Competition between researchers and developers will lead to the rapid spread of repair-based therapies once any such treatments start to be tested in earnest. The current enthusiasm and increased funding for clearance of senescent cells serves to illustrate this point. Clearance of senescent cells as a method of rejuvenation was a part of the SENS program from day one, but was ignored by near all of the research community until the first demonstrations were carried out. Now in a few short years, numerous approaches are showing far more robust and sizable effects on inflammatory age-related diseases than have yet been achieved via other methods.

Extension of healthy life span is inextricably linked with extension of overall life span when following a repair strategy. Health persists until unrepaired damage reaches critical levels. To the extent that damage can be repaired, health will last longer. To the extent that health lasts longer, life will last longer. So I think the present challenge is less a matter of where the focus on aging falls, but more a matter of obtaining that focus in the first place. It remains the case that work on therapies to treat aging as a medical condition is a minority concern, with minimal funding in comparison to research programs that only investigate aging. In turn, aging research as a whole has minimal funding in comparison to other fields of medical research. Given that aging is the majority cause of death in our species, and the cause of death of 90% of all people in the wealthier regions of the world that fund most life science research, this is a strange and unfortunate state of affairs. It isn't helped by researchers who declare that only minor gains are there to be had in our lifetimes, not exactly a way to fire up enthusiasm for the cause of human rejuvenation.

Shifting focus from life extension to 'healthspan' extension

Olshansky discusses how human longevity has reached into its upper limits and has little room for further gains. He notes that at the turn of the 20th century, life expectancy at birth in most developed nations ranged from 45 to 50 years. With the emergence of major public health initiatives in the late 19th century - including sanitation and the public provision of clean water - mortality rates dropped, and life expectancy increased rapidly. The rise in longevity has slowed considerably in recent decades, and maximum lifespan has never changed much throughout human history.

"There's been a lot of focus in the news lately about what is the maximum human lifespan, with some researchers claiming that it has the potential to be infinite, but there is a biologically based limit imposed largely by the way in which our bodies are designed, and it can be expressed mathematically." Based on the science and medicine available today, he contends that the probability of any significant increase in maximum lifespan in this century is remote.

"There is reason to be optimistic that future breakthroughs in aging biology, if pursued, could allow humanity to live healthier longer. You don't want to live to be over 100 years old if the last 20 years of your life are spent in pain and sickness. Ideally, you want to compress the years of decay and disease - what I call the 'red zone' - into as few as possible at the very end of life. We should not continue to pursue life extension without considering the health consequences of living longer lives. This will be the only way science can push through the biological barriers to life extension that exist today. Life extension should no longer be the primary goal of medicine when applied to people over age 65 - the principal outcome and most important metric of success should be extension of the healthspan."

From Lifespan to Healthspan

Over the past century, the relatively easy gains in life expectancy have been achieved by reducing mortality of younger people; more recently, scientists have focused on how much higher life expectancy can increase and what the maximum lifespan is for humans. The former is a population-based metric that involves national vital statistics for groups of people; the latter is the world record for longevity held by 1 person. Regarding maximum lifespan, only a small proportion of all humans are capable of living to 115 years of age. As such, the probability of any substantial increase in maximum lifespan in this century is remote.

Regarding life expectancy, one view developed in 1990 suggested that the increase in life expectancy would soon decelerate because the easy gains had already been achieved. Any substantive future increases require improvements in mortality at older ages, although components of the human body (e.g., brain, heart, knees) are not designed for long-term use. Others suggested that historical trends in the increase in life expectancy will continue indefinitely into the future due to yet-to-be-developed medical advances and improved lifestyles. Not one of the anticipated high-life-expectancy scenarios is remotely plausible today. In fact, a new trend in the opposite direction has emerged in much of the developed world, indicating that death rates for many major causes of death have either leveled off, experienced declining improvement, or increased since 2008.

Reductions in childhood diseases can occur only once for a population; once such gains are achieved, the only outlets for further gains in life expectancy must come from extending the lives of older people. Given that multiple fatal conditions accrue in older people because of biological aging. Once survival past age 65 years becomes common in a country, life expectancy gains will decelerate, even with medical advances and improved lifestyles. Because the point of diminishing returns on life expectancy and the longevity limit for the species has been approached in many parts of the world, there is good reason to conclude that the goal of life extension has largely been achieved.

The conventional approaches used to counteract the diseases of older age have been to improve behavioral risk factors, find ways to detect them earlier, and use medical technology to extend survival for those who already have diseases. The more important goal of public health, medicine, biotechnology, and the health sciences should now shift toward delaying and compressing the period of the lifespan when frailty and disability increase substantially. Referred to as the first health revolution, this new approach for public health (which is to target aging) is seen as a highly effective method of primary prevention.

A consortium of scientists as well as public health experts and organizations has formed with the purpose of developing this new approach to extend healthspan, address the diseases of aging, and help to ameliorate the economic challenges of an anticipated rising prevalence of late-onset diseases. This effort is called the Longevity Dividend Initiative or geroscience. Clinical trials designed to target aging have been approved by the US Food and Drug Administration, with the first trial set to begin in 2019. Large investments in aging biology have already begun through Google's Calico and Human Longevity Inc. The National Institute on Aging has established the Interventions Testing Program to rigorously and quickly test prospective aging interventions for free. The National Institutes of Health has reduced the barriers between its disease-oriented research silos, and the American Federation for Aging Research is spearheading a global effort to secure funds to launch the Longevity Dividend Initiative in 2019. The time has come to recognize the achievement of life extension. Efforts should be focused on achieving the goals of extending and improving the healthspan.

There is no real difference between modest aspirations and a determination to fail. Aim low, and the results will definitely be a disappointment. To pick one example, there is good evidence to suggest that the present outer limit on human life span is determined by accumulation of transthyretin amyloid in the cardiovascular system, leading to heart failure. This is what kills the majority of supercentenarians, based on autopsy data established after David Gobel of the Methuselah Foundation thought to ask Steven Coles of the Gerontology Research Group to check on cause of death. A number of companies are presently working on ways to clear transthyretin amyloid from the body, and there has been one quite successful clinical trial of such a methodology. What then happens to this vaunted limit on human lifespan once it is possible to remove this form of metabolic waste, a form of damage, that degrades cardiovascular function and kills the oldest people? All of aging is this way, all just damage that is amenable to repair.