Recently Published Research on Exercise and Aging

The human research that compellingly demonstrates that regular moderate exercise is very good for long term health is overwhelmingly epidemiological in nature. Researchers establish survey populations and mine existing data to find associations between health, aging, and exercise. The challenge here is always the identification of correlation versus causation: does exercise cause better health or does better health lead to more exercise? In many studies that has to be left an open question by the nature of the data and the study protocol - but some provide fairly compelling interpretations of causation.

Animal studies on the other hand leave absolutely no room for doubt on the question of exercise as a means to increase healthspan (if not maximum life span), improving long term health, slowing progression of measures of aging, and reducing incidence of age-related disease. It has been shown over and again in rigorous studies that exercise produces considerable improvements in health. The results, and the size of corresponding correlated health differences in human studies, are far better than can be achieved by any medical technology presently available in clinics.

For some researchers the data on exercise are a matter of backing up simple health advice: get out there and exercise in order to be healthier and extend your healthy life expectancy. But for others, this and investigations of the molecular biology of exercise form the ground floor for future development of exercise mimetic drugs. In an analogous way to ongoing work on calorie restriction mimetics, researchers will find ways to trigger some of the mechanisms of exercise to produce benefits without the exertion.

These research programs are producing and will continue to produce a wealth of data on how metabolism, aging, and lifestyle choices interact. But given that the benefits to health are already fully available the old-fashioned way, one has to think that perhaps all of this effort might be better directed towards research programs more likely to produce rejuvenation of the elderly - something that exercise and calorie restriction cannot achieve.

Road to exercise mimetics: targeting nuclear receptors in skeletal muscle

Skeletal muscle is the largest organ in the human body and is the major site for energy expenditure. It exhibits remarkable plasticity in response to physiological stimuli such as exercise. Physical exercise remodels skeletal muscle and enhances its capability to burn calories, which has been shown to be beneficial for many clinical conditions including the metabolic syndrome and cancer.

Nuclear receptors (NRs) comprise a class of transcription factors found only in metazoans that regulate major biological processes such as reproduction, development, and metabolism. Recent studies have demonstrated crucial roles for NRs and their co-regulators in the regulation of skeletal muscle energy metabolism and exercise-induced muscle remodeling. While nothing can fully replace exercise, development of exercise mimetics that enhance or even substitute for the beneficial effects of physical exercise would be of great benefit. The unique property of NRs that allows modulation by endogenous or synthetic ligands makes them bona fide therapeutic targets.

Exercise Training Initiated in Late Middle Age Attenuates Cardiac Fibrosis and Advanced Glycation End-product Accumulation in Senescent Rats

While it has long been postulated that exercise training attenuates the age-related decline in heart function normally associated with increased fibrosis and collagen cross-linking, the potential benefits associated with exercise training initiated later in life are currently unclear. To address this question, [rats] underwent treadmill-based exercise training starting in late middle age and continued into senescence (35 months) and were compared with age-matched sedentary rats.

Hearts were examined for fibrosis and advanced glycation end-products in the subendocardial layer of left ventricular cross-sections. Exercise training of late middle-aged rats attenuated fibrosis and collagen cross-linking, while also reducing age-related mortality between late middle age and senescence. This training was also associated with an attenuated advanced glycation end-product (AGE) accumulation with aging, suggesting a decrease in collagen cross-linking.

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