Exercise is the Best Longevity Drug

Aging. It’s something that we all do (some more successfully than others) yet something we all wish we didn’t. This isn’t some Peter Pan sort of fantasy — none of us really want to stay forever young, just maintain “youthfulness.”

Rather, the fear of aging inevitably stems from what aging brings — disease, wrinkles, physical and mental decline, among other maladies related to the passage of time. Nobody wants to age because nobody wants to act or feel old. It’s not the number that’s scary, but the acceptance of inferiority to our younger selves.

Aging (or technically, anti-aging) is a hot topic as of late. Multiple high-profile scientists are looking for ways to “cure aging” and some, to reverse it completely.

Presumably, finding the “fountain of youth” in the lab would allow humans to live longer out in the real world. Many aging scientists seek — if not immortality itself — to at least extend maximal human lifespan a decade or two. Getting humans to live to 130 or 140 would be quite the achievement.

A jump in average lifespan from around 80 to 100 or more would be a step-function change in human longevity — one that is probably a pipe dream given our current technologies. But it’s enticing nonetheless.

The promises of a longer life currently reside in interventions like calorie restriction (CR) — which has been shown to extend average and max lifespan in organisms like flies, worms, and even primates. In addition — molecular compounds like metformin, resveratrol, and rapamycin are showing promise in the lab (in mice) for lifespan and healthspan enhancement.

There is a wealth of new-age science to explore on the frontiers of aging research. But sometimes it’s valuable to consider the fact that simple interventions can produce potent physiological effects. That brings us to exercise, and it’s (potential) impact on lifespan.

I won’t belabor the point that exercise is a necessity for (super)successful aging. We know that exercise is efficacious for treating or preventing a cornucopia of diseases — including the disease of “getting old.” Given that physical function declines with age (we lose about 5–10% of our aerobic capacity per decade after about age 30), exercise is a counterattack against the time-driven process of muscular, cardiovascular, and cognitive decline.

For instance, a meta-analysis (a “study of studies”) indicated that getting adequate exercise could be associated with an additional 1–2 years of extra life, and that regular physical activity reduces the risk for all-cause mortality (death from “any cause”) and death from cardiovascular disease (CVD). Even more, this is a dose-response relationship — more exercise corresponds to a longer life.

Other studies have estimated that the risk of death is about 25–30% lower in physically active vs. inactive individuals — which might translate into an extra 3.5–4 years of life gained, on average.

In fact, nearly every single study that compares active to inactive people reports that the exercisers live longer! On top of this fact, people in those studies who are current and former athletes also live longer, suggesting that chronic regular exercise gives you an extra leg up.

Does how much you exercise matter? Yep — and so does how hard.

In a follow-up study of Harvard alumni (men) from 1966 to 1988, there was an inverse relationship between vigorous intensity physical activity and mortality — meaning that more energy expended during the week through physical activity yielded greater benefits for longevity. Another analysis of the same study found that low- and moderate-intensity exercise had little relation to mortality, but vigorous-intensity exercise noted a clear benefit. High-intensity interval training might just be the new longevity drug.

In the Harvard Health Alumni Study, only vigorous-intensity exercise was shown to have an association with longevity. Lee 1995

The above studies provide some compelling examples that exercise is perhaps a lifespan enhancer. But these types of associations come with their caveats. Association studies of physical activity commonly use self-report measures and are prospective — meaning that the participants fill out an activity questionnaire at one time point (to estimate how much they exercise) and are then followed up for a certain amount of years with the outcome (dying, for example) tracked and reported.

While we can observe a positive correlation of physical activity and lifespan, this is hypothesis-generating, at best. We can’t claim that exercise causes an increased lifespan per se. Indeed — people who exercise are more likely to engage in other positive lifestyle habits like eating a healthy diet, not smoking, using less alcohol, and (maybe) having a higher socioeconomic status.

In research, this is known as the “healthy user bias.” Positive lifestyle behaviors tend to cluster in individuals. Since all of these factors also influence longevity, they make it impossible to isolate the influence of exercise on lifespan.

Fortunately, we can look for an association of longevity with a physiological outcome that is tightly related to physical activity — aerobic fitness. Direct measures of fitness could provide even more robust data for the association of exercise and longevity, since it tells us more about the “status” of the body than a physical activity questionnaire does.

A recent study in the Journal of the American Medical Association (JAMA) found evidence that a greater cardiorespiratory fitness predicted a lower risk of death. With access to exercise treadmill tests — or V02 max tests — they were able to gather data on over 120,000 individuals on whom they also had access to death records (all-cause mortality was the primary outcome).

Survival probability for groups stratified by aerobic fitness (performance). Mandsager 2018

Not only did higher aerobic fitness predict a reduced death risk, but those who were categorized as “elite performers” (who had V02 max levels >2 standard deviations above the average for their age) had the lowest risk of death in the entire study.

This finding was “surprising” to some at first amid some newer published data that indicates “extreme” endurance exercise may have cardiovascular consequences. That’s not exactly what this particular study says, though it’s hard to determine if any participants in this study meet the definition of “extreme exercisers.” All we know is that they had a higher aerobic capacity — whether they exercised more or not is unknown. This is important to point out since a good portion of V02 max is genetic — i.e. influenced by genes more so than lifestyle.

As for why exercise might increase lifespan? We have plenty of exercise studies in humans that tell us how exercise improves cardiovascular health and function, increases skeletal muscle mass and performance, reduces risk factors for disease, and improves cognitive abilities (to name a few). It is likely that synergistic effects of exercise at a whole-system level combine to reduce disease risk, maintain physiological function, and increase lifespan as a result.

To be frank, I don’t think exercise gets enough of the spotlight when it comes to healthspan and lifespan. Much of the focus (especially recently) has been on diet and, to a lesser extent, potential lifespan-enhancing pharmacological agents.

I won’t downplay diet — it has an enormous role to play in living a healthy and long life. While I’m not so keen on the phrase “you can’t outrun a bad diet” — this is probably the harsh truth for most people.

As far as pharmacological agents go — these too may have their place in a future where lifespan enhancement is a strategy available to all. Lots of studies in animal models show promise. Perhaps one day we will pop a lifespan pill to boost our chances of being a centenarian.

Exercise is the ultimate biohack, and it doesn’t get enough credit.

As we search for the evasive fountain of youth or to create the ultimate cocktail of longevity drugs, let’s not forget that if we feed our evolutionary roots by moving like we were meant to, we can maintain our health— perhaps for a long, long time.

Source: https://www.broadinstitute.org/epigenomics/epigenome-mapping

References

Reimers CD, Knapp G, Reimers AK. Does physical activity increase life expectancy? A review of the literature. J Aging Res. 2012;2012:243958.

Gremeaux V, Gayda M, Lepers R, Sosner P, Juneau M, Nigam A. Exercise and longevity. Maturitas. 2012;73(4):312–7.

Lee IM, Paffenbarger RS. Associations of light, moderate, and vigorous intensity physical activity with longevity. The Harvard Alumni Health Study. Am J Epidemiol. 2000;151(3):293–9.

Mandsager K, Harb S, Cremer P, Phelan D, Nissen SE, Jaber W. Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing. JAMA Netw Open. 2018;1(6):e183605.

Lee I, Hsieh C, Paffenbarger RS. Exercise Intensity and Longevity in Men: The Harvard Alumni Health Study. JAMA. 1995;273(15):1179–1184. doi:10.1001/jama.1995.03520390039030

PhD candidate at the University of Florida — Science writing with a particular focus on exercise and nutrition interventions, aging, health, and disease.

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