Exercise as a calorie restriction mimetic?

According to a recent study by Lanza et al., endurance exercise increases mitochondrial protein levels, metabolic enzyme activity, and expression of SIRT3 (a sirtuin thought to be involved in longevity assurance). At the organismal level, insulin sensitivity goes up (this is good: insulin resistance leads to type II diabetes) and gluconeogenesis goes down.

So far, so good, but hardly surprising: file under “exercise is good for you, item #68232”. The interesting bit is that the mitochondrial and other changes are very similar to the physiological consequences of calorie restriction (CR), an intervention that is known to extend lifespan in model organisms and to delay age-related disease in humans. The authors argue that exercise may promote longevity through the same pathways as CR.

This fits in nicely with recent observations connecting exercise and CR: for example, resveratrol, thought to be a CR mimetic, improves exercise tolerance in mice, consistent with the idea that exercise and CR have something in common.

The next obvious question: Do exercise mimetics also promote longevity, and if so, do they do so by the same mechanism as CR?

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9 comments

  1. Very nice post. To give a bit more background, most exercise studies in rodents shows around a 6-12 % improvement in lifespan, while CR typically shows 20-40%. It would be interesting to see what combining execise and a low level of CR (something that is easier to follow than the typical 25-40% CR levels) would do for lifespan. Or combining exercise/CR mimetics along with exercise and low levels of CR (or at least not overeating).

  2. All:

    To give more background on Ward’s background: exercise studies show modest improvements in mean longevity, but none on maximum lifespan. This is generally accepted to mean that exercise reduces the risk of *premature* death from early-onset disease, but doesn’t affect basic aging processes. This is consistent with human epidemiology, where the benefits of lifelong exercise are generally in the 1-2 year range, and never more than 3. Moreover, lifelong exercise doesn’t even slow down most of the age-related decrements in muscle structure and function in rodents, and similarly in humans master athletes remain more fit than sedentary people for most of their lives but then suffer a sudden dropoff in performance after ~ age 70.

    CR, by contrast, is taken to actually retard aging because it dose-dependently extends mean and maximum lifespan, preserves physiological function, and reduces damage to muscle cells and neuromuscular units.

    So since exercise itself clearly does not mimic CR, an exercise-mimetic would not be expected to be a CR-mimetic.

  3. Michael,

    thanks for giving a more thorough, and better, background than I provided. I was trying to convey the general points you did, but you did a better job. Though I would still encourage people to exercise (for numerous reasons) it does not appear to be the answer for large gains in longevity.

  4. It’s pretty clear from the paper cited above, and other studies of gene expression, that exercise does phenocopy CR to some extent, but not in every sense. One synthesis of these observations with Michael’s point would be that the shared aspects (specifically, related to mitochondrial changes) have to do with increasing average lifespan whereas the CR-specific aspects have to do with increasing maximum lifespan.

    Michael — could we get a citation on the “1-2 years” figure related to lifelong exercise? I have a talk I give on the benefits of aging research vs. other methods of extending lifespan, and I’d love to include exercise. In the current version, I only cite the disease-related statistics from Olshansky et al. but I would definitely include this figure as well if I knew the source. Thanks in advance!

  5. Hi Chris,

    Citations: (I won’t include links, as WordPress tends to frown thereon):

    ***********
    “A natural history of athleticism, health and longevity”
    Authors: Paffenbarger R.S.; Lee I.-M.

    Source: Journal of Sports Sciences, Volume 16, Supplement 1, 1 May 1998 , pp. 31-45(15)
    (Go to Informaworld: it’s not MEDLINEd for some reason).
    *****
    Cf. PMID: 3945246, also from this group; you may also be interested in their PMID: 10670554 and 7707624 on exercise intensity and quantity; PMID: 8426621 on ADOPTING exercise and other healthy behaviors.

    See also Table 3 from PMID: 11434797, which I think you’d find more broadly useful for your talk (have a gander at the rest of the Table and Figs 2-4).

    I know there are others, tho’ they’re not coming immediately to mind; one problem is that so much of the epidemiology is at best in mortality *rates* during a specified window, not actual life expectancy.

    -Michael

  6. Thanks for the citations, Michael.

    Given how broad an effect exercise has (i.e., on multiple organ systems in the body), I’m really rather surprised to see how small of an effect exercise has on lifespan. Then again, I guess it makes sense that the net effect of exercise would be smaller than a hypothetical cure for all CVD, which is the basis of the Olshansky et al projections.

  7. To give more background on Ward’s background: exercise studies show modest improvements in mean longevity, but none on maximum lifespan. This is generally accepted to mean that exercise reduces the risk of *premature* death from early-onset disease, but doesn’t affect basic aging processes. This is consistent with human epidemiology, where the benefits of lifelong exercise are generally in the 1-2 year range, and never more than 3.

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