Aging and Caloric Restriction Research: A Biological Perspective With Translational Potential

Abstract

Aging as a research pursuit is fairly new compared with traditional lines of medical research. A growing field of investigators is focused on understanding how changes in tissue biology, physiology, and systemic homeostasis, conspire to create increased vulnerability to disease as a function of age. Aging research as a discipline is necessarily broad; in part because aging itself is multi-faceted and in part because different model systems are employed to define the underlying biology. In this review we outline aspects of aging research that are likely to uncover the pivotal events leading to age-related disease vulnerability. We focus on studies of human aging and discuss the value of research on caloric restriction, an intervention with proven efficacy in delaying aging. We propose that studies such as these will deliver target factors and processes that create vulnerability in human aging, an advance that would potentially be transformative in clinical care.

Keywords: Aging; Caloric restriction; Humans; Metabolism; Nonhuman primates.

Fig. 1

Caloric Restriction (CR) delays the onset of age-related diseases. Studies in rodents and nonhuman primates have revealed a beneficial effect of CR on a diverse set of conditions related to human aging.

Fig. 2

Metabolic regulators are among the strongest candidates as ‘effectors’ in the mechanisms of delayed aging with CR. These nutrient and energy sensing factors receive extracellular and intracellular signals via indicator molecules to implement various actions in pathways related to growth, metabolism, and inflammation.

Fig. 3

Proposed scheme for integrated studies to define and implement delayed aging. Caloric restriction (CR) provides mechanistic insights into signaling pathways and processes that regulate longevity. Factors and processes implicated in CR's mechanisms are very strong candidates for the development of drugs and treatments to enhance healthy aging in humans. These factors can be crosschecked against the growing body of work on human aging biology, and interventions developed from these avenues can be tested for translatability in nonhuman primate models before being proposed for human trials.