Fight Aging!

An interesting open access paper on exercise in identical and non-identical twin pairs was recently published, the data suggesting that long-term differences in physical activity between identical twins don't result in any significant difference in longevity, even though other differences in health outcomes are observed. We might draw parallels between this and similar results observed in a mouse study from a few years back, in which the exercising mice had better health but no increase in maximum life span. The researchers here theorize that the well-known epidemiological association between exercise and increased life expectancy is perhaps as much a matter of genetics as of choice.

For any observed statistical relationship in humans there are always questions of causation. This is especially true in the web of associations related to aging and mortality in population data, in which life expectancy, wealth, social status, intelligence, education, exercise, diet, and culture all have ties to one another. That we pay great attention to these relationships is a function of having no good way to treat aging, I've long thought: we care about trivial differences in life expectancy of a few years here and a few years there because this is all that is in our power to change right now, and that will continue until the development of rejuvenation therapies. Life expectancy and exercise are linked robustly in many data sets, and even more so now that accelerometers are so cheap and ubiquitous that even large studies can use them to obtain actual rather than self-reported data on physical activity. There are studies to demonstrate longer life expectancy in athletes, longer life expectancy in those who exercise modestly versus those who are sedentary, and so forth. What are these studies measuring, however? For example, what if people who are more robust and would live longer regardless of exercise tend to exercise more? Or perhaps exercise levels are a good proxy for lower levels of visceral fat tissue and consequent chronic inflammation - themselves linked to greater risk of age-related disease and mortality.

The results of this study definitely muddy the waters in the search for causation and mechanism in exercise and mortality reduction, providing evidence to support a state of considerable complexity in the relationship between exercise, genetics, and outcomes in health. Nothing in biology is ever as simple as we'd like it to be, so this should perhaps be expected. Regardless he data presented below should be added to the many past studies on exercise and mortality, and its weight balanced accordingly - never take any single set of data and interpretations as gospel in science. This doesn't change the consensus, which is that you should exercise, and that you are expected to obtain benefits by doing so. It does add subtlety to the picture, however.

Lifespan - genetic background and physical activity

Animal studies have already shown that a strong link exists between genetic background and physical activity level. The purpose of our study was to investigate the associations between genetic background, physical activity level, and lifespan. We studied also both identical and non-identical same sex twin pairs of which one was physically active and his/hers co-twin was inactive. We looked for the association between physical activity level and lifespan by following the mortality of the twins for 23 years.

High physical activity level was associated with longer lifespan when looking at non-identical twins that differ for their genetic background. However, in identical twins, that share the same genetic background, in pairwise analyses comparing physically active members of a twin pair with their inactive co-twin, there was no difference in lifespan. Our results are consistent with previous findings, that animals that have high aerobic capacity are physically more active compared to animals with low aerobic capacity. The findings in human twins were in agreement with this: discordance in physical activity level was clearly more common among non-identical twins than in identical twins showing an effect of genetic background on physical activity level.

Vigorous physical activity in adulthood did not increase lifespan in human twins, even though physical activity is well-known to have various positive effects on health, physical fitness, and physical function. Based on our findings, we propose that genetic factors might partly explain the frequently observed associations between high physical activity level and later reduced mortality in humans. Our finding covers vigorous physical activity started at adulthood, hence physical activity started during childhood may have different effects. Thus, it will be critical to determine whether physical activity has a positive effect on lifespan when commenced early in life.

Physical activity in adulthood: genes and mortality

Observational studies report a strong inverse relationship between leisure-time physical activity and all-cause mortality. Despite suggestive evidence from population-based associations, scientists have not been able to show a beneficial effect of physical activity on the risk of death in controlled intervention studies among individuals who have been healthy at baseline. On the other hand, high cardiorespiratory fitness is known to be a strong predictor of reduced mortality, even more robust than physical activity level itself. Here, in both animals and/or human twins, we show that the same genetic factors influence physical activity levels, cardiorespiratory fitness, and risk of death. Based on both our animal and human findings, we propose that genetic pleiotropy might partly explain the frequently observed associations between high baseline physical activity and later reduced mortality in humans.

The prospective Finnish Twin Cohort includes all same-sex twin pairs born in Finland before 1958. Physical activity was measured with a structured questionnaire. We used persistence and changes in vigorous physical activity during the years 1975, 1981, and 1990 as baseline predictors of mortality. Altogether, 11,325 twin individuals (4190 complete twin pairs) answered the required physical activity questions for all three baseline time points. Of the 4190 same-sex twin pairs, we identified 179 persistently discordant for participation in vigorous physical activity.

Taken together, our results are consistent with previous data on rodents and humans, which indicated that genetic predisposition plays a significant role in exercise participation. These results are also consistent with our previous suggestion that genetic pleiotropy may partly explain the associations observed between high physical activity and mortality in our past epidemiological studies, which called for high quality intervention studies to analyse the true effects of physical activity on morbidity and mortality among initially healthy individuals. Our results also support the notion that inherited aerobic capacity is a predictor of longevity, but further study in both animals and humans is required to determine whether this is true for the portion of aerobic capacity enhanced by vigorous physical activity. Our findings are also consistent with previous studies that show positive effects of physical activity on glucose metabolism in rodents and human twins. However, vigorous physical activity does not improve longevity in twins or rodents, particularly when commenced in maturity. It is to note that randomized controlled trials show that vigorous physical activity has other health benefits.