Exercise Differences Do Not Produce Longevity Differences in Identical Twins

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.

Comments

We know that people who exercise live longer (e.g., http://www.hindawi.com/journals/jar/2012/243958/abs/). There are two possible explanations. Either people who exercise more are genetically wired to like exercise more, and they, coincidentally, live longer. Or it is the exercise itself that is beneficial. These studies point in the first direction. Yet there is overwhelming evidence that exercise, even when started very late in life, has beneficial effects on health. Why won't better health translate into longer life? Could be that there is a trade-off involved where you get many health benefits, but other health markers are degraded. As far as I can tell, this has never been identified. (Over-exercising is definitively possible but affects a tiny minority of gym nuts.)

If you look at the Nature paper, the mice were fed ad libitum with the runner mice eating significantly more (because they were females and females act that way). So exercising and eating more is bad. The experimenters could have controlled the food intake, but they did not on purpose, because doing so might have amounted to caloric restriction and lead, they imply, to longer lives.

I am not sure that this is satisfying. It would have been better to have a control group where runners are given the same amount of food as the non-runners. Then we could have told what the effect of running is, per se. But it seems that we know the answer: longer lives.

Still in the Nature paper, they find that in the non-identical same-sex twins (179 pairs), there is a significant benefit to exercising, but in the identical same-sex twins (34 pairs), there is no significant benefit. What is interesting there are the figures:

http://www.nature.com/articles/srep18259/figures/3

From the last one, they conclude persistent physical activity does not lead to an increased lifespan. It is evident from the shape of the curves that their conclusion relies on a few deaths... and is not very robust statistically. We could equally conclude that the blue lines are better curves... In any case, the results do not appear to be so conclusive as they make it seem in the text.

Whatever the truth might be, what is evident is that exercise is robustly associated with better health and longer lifespan.

Posted by: Daniel Lemire at December 21st, 2015 1:13 PM

@Daniel Lemire

< < Salut Daniel ! C'est-tu le cas de le dire ou non. C't'assez paradoxal, right ? >>. My take on this is that in high age, exercise can not overcome the effects of gene predisposition (the ones that were inscribed in you long ago and that 'pre'-determined your life from decades ago, near birth/young adolescence...many studies show that that early part of life (and oxidative stress accrual then) has far more meaning that we can give it credit; what you do later on 'in second part of life' definitely has some effect; but what happened in the 'first part' (childhood) as tremendous precedence over what (will) happen(s) in second part; because what happened in the first is permanent and in you (genetically speaking, you're bound by it even for all efforts); so in the 2nd part,; it's all about juggling what happened in the first and how 'bad' it happened back then.For example, late puberty is mark of centenarians and oftenly 'growing too fast' at early chilhood is not a good sign (longevity wise) for growth is on accelerated, which allows stochastic damage faster during cell cycle growth/ proliferation at that age (in fact, studies show high loss of telomeres during growth phase of childhood to adolescent and than adult, basically hormonal/endocrinal sexual maturity/puberty by testosterone and oestrogen is highly costly on telomeres; as adulthood sets in telomere attrition abates and for the next decades telomere attrition is at its lowest from slowed metabolism with age). If we transponse that with exercice, we can see benefits, like improving health via PGC-1a/b (wih PPARGC1A Peroxisome proliferator-activated receptor-γ coactivator), PGC is master regulator of energy and metabolism through fat burning pathway, insulinotropic and regulation of glycemic metabolism. Without, PGC, exercice is futile and wouldn't give any result (as seen in mice that do exercice and have PGC-knock out); for almost all beneficial results of exercice stem from PGC activation. PGC is not magic silver bullet though and it can't stop the tides of aging and damge accrual (through 3 main pathways, replicative senescence, oncongene-induce and random dna damage). Hence, exercice is no magic either. It has tremendous (via PGC) boost on health and of course, if you keep your health you allow a long average lifespan.
Myself, I am a twin (I have a twin sister whom is 32 minutes younger than me : D, being a guy, obviously I don't apply to identical twins) but clearly, I can relate to this study for one I am a twin and two, I saw a few things with aging, compared to my sis. She too remains, like me, very fit and thin....yet she is Not at all a health nut and does small amounts of exercise altogether. She is in perfect health condition (or so it seems) and she sometimes smokes cigarettes; so you see where I'm getting at....genes are in play here far more, than doing exercise. If you had greta genetics, exercisig will only make that come out even more (as in this study) but if not, all the exercise in the world Will Not save you.

Centenarians are a perfect example. Some did exercice, it helped them alot to get there (with their genetics of course). But Some barely did no exercise in their life....ate crap food, smoked, drank did everything possible to Kill themselves...it didn't happen..they still lived to 100+, heck even 110+, they are an anomaly as some put it and a very rare one. Other people (like us possibly) may not be so lucky and we can try our best to postpone our genetic predisposition with doing exercice but will not stop the Fate coming for us; only abate it/postpone it a little.

I'm going to tell you a very Telling example: My uncle recently died at 73 years old of Alzheimer's disease. He was the antithesis of the Centenarian who did nothing, no exerice, eat fat sugarry salty stuff, smoke like a chimney, drink like a hole, etc...and still lived to be a centenarian. Well, he was eating right, never smoked, barely drank ever, and was Exercise Machine. He was basically a Marathon runner - but in bicycle. He was quite fit (he maintained a healthy BMI body mass index for 70 year old)...because of his extreme exercise endurance in bike (like biking from god knows where to god knows where - very Far...tons of miles...one city to another) day on and day out, exercising nearly every day for hours (I guess that was his retirement...lots 'of workout' in cycling..not so re-Tiring...more like tiring to me from exhaustion). Well...He died....in less than 6 months everything went haywire and consciouness faculties were lost gradually..it's like what can do you right ? Do more exercise..? No it does notthing at that point...Azlheimer's is a deadly disease once it gets to your head and you lose your memory capacity as the amyloid plaques make your brain like a swiss cheese filled with holes and prune like a shrinking drying prune (< >). So for all his effors, it seemed like in vain, you don't decide what happens, genes do. Exercise post-pones things a bit and most likely, had he not been a exercise 'freak', who would have died Much quicker (say in his 50-60s, rather than 73).

But you are righ though, exercise is in general very helpful, health wise and thus improves, average lifespan - in general. There is no hurt in trying to keep fit and healthy by exercising. That's the key word, but not for everybody (as seen from uncle example, exercise can be futile at some point). Inherited genetics will decide, much more as you age, wether you continue to live.

Posted by: CANanonymity at December 22nd, 2015 8:39 AM

Perhaps this is part of the puzzle in at least one of the studies: "Vigorous physical activity in adulthood did not increase lifespan in human twins." As anyone who follows this blog knows it is unclear that vigorous physical activity improves longevity, as opposed to moderate exercise.

Posted by: KC at December 22nd, 2015 12:34 PM

@CANanonymity

Inherited genetics will decide, much more as you age, wether you continue to live.

While this is true, I don't think it contradicts the importance of maintaining a reasonable exercise program as you age. In fact, an argument can be made that exercising becomes more important as you age... after all, we are all fit when we are 20.

Posted by: Daniel Lemire at December 22nd, 2015 1:10 PM

@KC

Hi KC! Yes, there is that. The paper (is open access 1.) and continuously uses the word 'vigorously', but does not quantify it/characterize it exactly. But it does say 'vigorous' exercise with pointing to the 'vigorous' exercise study (2., also open access) that specifies what they mean by use of that word for the type of exercise.
They specify :

'' On the basis of different studies, genetic determination of physical activity varies from low to moderately high, the genetic contribution being higher for vigorous activity than for nonvigorous activity...

Assessment of participation in vigorous physical activity was based on the following question: “Is your physical activity during leisure time about as strenuous, on average, as: 1) walking, 2) alternately walking and jogging, 3) jogging (light running), or 4) running?” Those who chose alternative 2, 3, or 4 were classified as participating in vigorous activity.''

Now this answers what they meant by Vigorous activity...well to be honest, it isn't That vigorous, it's mostly leisurely, sure you can run for miles, but we are not talking abou lifting 300lbs, doing set up crunch push ups, whole nine years either...walking..jogging, running..that is not Super vigorous...ok perhaps running a marathon is, for you need endurance, but this is not really the case here. That undermines the power of exercise and also undermines the theory that exhaustion is the reason there is a discrepancy between 'light/moderate' exercise people vs Athletes who do exercise truly Vigorously that would younger. Because exhaustion can have severe effect, even deadly (as seen some marathon runners who die mid-running or a the end of marathon), but overall means that Athletes have a boost and it will help them live longer from that Extra exercise. As such, muddy the whole thing about exercise and help to give precedence to genes dictating these non-sensical outcomes.
In the end, it depends on your body, if it not accustomed to higher demand, there is no point, you have to start slow and build up to become an athlete. Like the saying goes : ''You can't run before learning to walk first''.

Still, the takeaway message, just do some exercise and it won't matter all that much for your longevity (genes will) but will maintain your health a bit longer.

1. http://www.nature.com/articles/srep18259
2. http://aje.oxfordjournals.org/content/156/11/985.long

Posted by: CANanonymity at December 22nd, 2015 1:58 PM

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