A Near Future of Gymnomimetics

If, as seems to be the case, it is possible to design drugs to make a mammal's metabolism behave in a similarly beneficial way to the state induced by calorie restriction, then we should also believe that the same can be done for exercise. The results of exercise are, like the results of calorie restriction, nothing more than altered metabolic processes and the consequences thereof: better health and a modestly extended life span. However, as for all methods of slowing aging, this will be of little benefit to those of us already middle aged today. We will be old by the time therapies arrive, which means we need to see progress underway in ways to repair and reverse the damage of aging, not just slow it down.

Given that interest in slowing aging is dominant amongst gerontologists, I think it plausible that work on metabolic manipulation will continue to expand. If the controlling mechanisms of exercise-induced metabolic changes can be isolated and manipulated - and there is no reason to think that this is impossible, or that it will require more than a decade or two to accomplish - then the present excitement over calorie restriction mimetic drugs may soon grow to include potential exercise mimetics.

For example:

Regular physical activity and especially aerobic exercise are associated with reduced risk of disease and enhanced longevity, but the molecular mechanisms of these health benefits remain obscure. A comprehensive metabolomic approach was used to characterize the changes in blood levels of [more than] 200 metabolites upon vigorous exercise and identified two dozen that changed substantially. One, niacinamide, is intimately related to the metabolism of nicotinamide adenine dinucleotide (NAD+) and its reduced form NADH, which is in turn linked with exercise capacity as well as health status.

Intensive investigation of metabolic changes with exercise could lead to pharmacological attempts to mimic the beneficial effects of exercise, an approach we term "gymnomimetics."

If you dig back into the way in which mitochondrial damage contributes to aging, you'll see that the cycle of NAD+ to NADH and back again plays an important role in spreading the consequences of damaged mitochondria beyond the cell that contains them. But NAD+ and NADH appear in many other processes of interest to those who study aging and metabolism. It is not surprising to see their levels change with environmental circumstances that impact health and longevity.


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