Calorie Restriction and Aging in Humans

Abstract

Calorie restriction (CR), the reduction of dietary intake below energy requirements while maintaining optimal nutrition, is the only known nutritional intervention with the potential to attenuate aging. Evidence from observational, preclinical, and clinical trials suggests the ability to increase life span by 1-5 years with an improvement in health span and quality of life. CR moderates intrinsic processes of aging through cellular and metabolic adaptations and reducing risk for the development of many cardiometabolic diseases. Yet, implementation of CR may require unique considerations for the elderly and other specific populations. The objectives of this review are to summarize the evidence for CR to modify primary and secondary aging; present caveats for implementation in special populations; describe newer, alternative approaches that have comparative effectiveness and fewer deleterious effects; and provide thoughts on the future of this important field of study.

Keywords: CALERIE; aging; calorie restriction; intermittent fasting; metabolic adaptation.

Figure 1

Schematic of the effects of primary and secondary aging on life span. The rate of decline in physiological functions is associated with mammalian life span. The penultimate rate of aging, whereby health span is prolonged and the majority of life is lived free of disease and with optimal physical and cognitive function, leads to above-average life span. An increase in the rate of decline of physiological function, due to the primary causes of aging and with the influence of secondary causes, leads to a shorter life.

Figure 2

Proposed effects of calorie restriction (CR) on primary and secondary aging. Primary and secondary aging act independently and synergistically to produce stressors that induce molecular, cellular, and systemic changes. CR broadly improves aging through these processes. Abbreviation: CVD, cardiovascular disease.

Figure 3

Symmetries, differences, and unknowns in normal aging versus aging with calorie restriction (CR). (a) Aging in a hypercaloric environment presents many physiological stressors, resulting in unhealthy aging. (b) While aging with CR shares some similarities with aging in a hypercaloric environment, how these changes affect healthy aging (i.e., cognition, cardiometabolic diseases, and physical functioning) in elderly populations is unknown. Abbreviation: CVD, cardiovascular disease.