For millennia, the consensus of the general public has been that aging is inevitable.
For most of our history, even getting to old age was a significant accomplishment – and while centenarians have
been around at least since the time of the Greeks, aging was never of major interest to medicine.
That has changed. Longevity medicine has entered the mainstream. First, evidence accumulated that lifestyle
modifications prevent chronic diseases of aging and extend healthspan, the healthy and highly functional period of
life. More recently, longevity research has made great progress – aging has been found to be malleable and
hundreds of interventional strategies have been identified that extend lifespan and healthspan in animal
models.
Human clinical studies are underway, and already early results suggest that the biological age of an individual
is modifiable.
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A concerted effort has been made in the longevity field to institutionalize the word “healthspan”. Why
healthspan (how long we stay healthy) and not its side-effect of lifespan (how long we live)?
The reasons are linked more to perception than reality. Fundamental to this need to highlight healthspan is the
idea that individuals get when they are asked if they want to live longer. Many imagine their parents or
grandparents at the end of their lives when they often have major health issues and low quality of life. Then
they conclude that they would not choose to live longer in that condition.
This is counter to longevity research findings, which show that it is possible to intervene in late middle life
and extend both healthspan and lifespan simultaneously. Emphasizing healthspan also reduces concerns of some
individuals about whether it is ethical to live longer.
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A drawback of this exists, though: many current longevity interventions may extend healthspan more than lifespan.
Lifestyle interventions such as exercise probably fit this mold. Many interventions that have dramatic
health-extending effects in invertebrate models have more modest effects in mice, and there is a concern that they
will be further reduced in humans.
In other words, the drugs and small molecules that we are excited about today may, despite their hefty
development costs and lengthy approval processes, only extend average healthspan by five or ten years and may not
extend maximum lifespan at all.
Make no mistake, this would still represent a revolution in medical practice!
A five-year extension in human healthspan, with equitable access for all people, would save trillions per year in
healthcare costs, provide extra life quality across the entire population and ameliorate the demographic
challenges that are happening in the first half of this century.
Most experts in the field now acknowledge that this is a likely outcome in the near future and one focus of
longevity medicine is now on achieving it. But far more is possible.
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Arguably, the avoidance of an emphasis on lifespan is a consequence of an overly pragmatic approach to two
fundamental questions:
Why do humans age and what can we do about it?
These are surely two of the biggest questions in human biology. Although we try our best to ignore it, the
prospect of an inevitable decline in health leading to mortality shapes our thoughts and actions. Despite the
incredible advances in longevity research, these questions remain unanswered.
- What biological processes bring about the aged state?
- Can aging not just be significantly slowed, but more and more thoroughly reversed?
- How would humans, and their societies, be different if we achieve these goals?
It will cost billions of dollars in research and significant time to answer such questions, but we assert that it
would undoubtedly pay for itself many times over. The case can (and will) be made that these questions should be
answered because the knowledge gained will inevitably lead to major medical advances.
Another reason is the one that is not utility-driven, but rather the classic “knowledge for knowledge’s sake”
argument. Understanding ourselves and the organisms around us used to be reason alone to do research, and
answering basic questions reliably yields utility in the future. Penicillin comes to mind! But the quest for
knowledge, especially on ubiquitous topics such as aging, is worthy in its own right.
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Achieving much better control of aging would not mean immortality, of course. Nevertheless, it would dramatically
change the world we live in and how we live in it. Life quality may expand, fear of loss of independence may
diminish and, over time, the fabric of our world may radically improve.
What would it mean?
- Imagine the energy of youth combined with the wisdom of experience.
- Think about living long enough for space travel.
- Imagine going back to school at 80 to study the latest in scientific breakthroughs, starting a new career,
seeing your great-great-grandkids.
Yes, there will be unexpected outcomes and some might raise new challenges — but the same was true of past
technological advances that few of us would give back.
How many of us want to go back in time now? How many will want to in the future?
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Optimism about a better future drives us still, and one way to move forward is to answer the big questions in
biology. The grand challenge of aging is foremost among these.
What cards need to be turned over to answer the longevity question? What interventional strategies are likely to
