Molecular mechanisms of life- and health-span extension: role of calorie restriction and exercise intervention.
The aging process results in a gradual and progressive structural deterioration of biomolecular and cellular compartments and is associated with many pathological conditions, including cardiovascular disease, stroke, Alzheimer's disease, osteoporosis, sarcopenia, and liver dysfunction. Concomitantly, each of these conditions is associated with progressive functional decline, loss of independence, and ultimately disability. Because disabled individuals require care in outpatient or home care settings, and in light of the social, emotional, and fiscal burden associated with caring for an ever-increasing elderly population, research in geriatric medicine has recently focused on the biological mechanisms that are involved in the progression towards functional decline and disability to better design treatment and intervention strategies. Although not completely understood, the mechanisms underlying the aging process may partly involve inflammatory processes, oxidative damage, mitochondrial dysfunction, and apoptotic tissue degeneration. These hypotheses are based on epidemiological evidence and data from animal models of aging, as well as interventional studies. Findings from these studies have identified possible strategies to decrease the incidence of age-related diseases and delay the aging process. For example, lifelong exercise is known to extend mean life-span, whereas calorie restriction (CR) increases both mean and maximum life-span in a variety of species. Optimal application of these intervention strategies in the elderly may positively affect health-related outcomes and possibly longevity. Therefore, the scope of this article is to (i) provide an interpretation of various theories of aging from a "health-span" perspective; (ii) describe interventional testing in animals (CR and exercise); and (iii) provide a translational interpretation of these data.
Department of Aging and Geriatric Research, Division of Biology of Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA. ccarter@aging.ufl.edu
Christy S
CS
Carter
Tim
T
Hofer
Arnold Y
AY
Seo
Christian
C
Leeuwenburgh
D000818:Animals; D031204:Caloric Restriction; D002149:Energy Intake / Q000502:physiology*; D015444:Exercise / Q000502:physiology*; D006801:Humans; D008136:Longevity / Q000502:physiology*