Somatic growth, aging, and longevity

Abstract

Although larger species of animals typically live longer than smaller species, the relationship of body size to longevity within a species is generally opposite. The longevity advantage of smaller individuals can be considerable and is best documented in laboratory mice and in domestic dogs. Importantly, it appears to apply broadly, including humans. It is not known whether theses associations represent causal links between various developmental and physiological mechanisms affecting growth and/or aging. However, variations in growth hormone (GH) signaling are likely involved because GH is a key stimulator of somatic growth, and apparently also exerts various "pro-aging" effects. Mechanisms linking GH, somatic growth, adult body size, aging, and lifespan likely involve target of rapamycin (TOR), particularly one of its signaling complexes, mTORC1, as well as various adjustments in mitochondrial function, energy metabolism, thermogenesis, inflammation, and insulin signaling. Somatic growth, aging, and longevity are also influenced by a variety of hormonal and nutritional signals, and much work will be needed to answer the question of why smaller individuals may be likely to live longer.

Fig. 1

Negative association of adult body size and longevity may result from impact of the underlying metabolic process on both somatic growth and aging (top panel) or, presumably less likely, from the negative effects of growth and adult body size on the rate of aging and longevity (bottom panel)