Bartke Andrzej
Department of Internal Medicine, Southern Illinois University School of Medicine, 801N. Rutledge, P.O. Box 19628, Springfield, IL 62794-9628 USA.
NPJ Aging Mech Dis. 2017 Sep 29;3:14. doi: 10.1038/s41514-017-0014-y. eCollection 2017.
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.
虽然较大体型的动物通常比较小体型的动物寿命更长，但在一个物种内，体型与寿命的关系通常相反。较小个体的寿命优势可能相当可观，在实验室小鼠和家犬中对此有最充分的记录。重要的是，这种现象似乎广泛适用，包括人类。尚不清楚这些关联是否代表影响生长和/或衰老的各种发育和生理机制之间的因果联系。然而，生长激素（GH）信号的变化可能与之有关，因为GH是体细胞生长的关键刺激因子，而且显然还会产生各种“促衰老”作用。将GH、体细胞生长、成年体型、衰老和寿命联系起来的机制可能涉及雷帕霉素靶蛋白（TOR），特别是其信号复合物之一mTORC1，以及线粒体功能、能量代谢、产热、炎症和胰岛素信号的各种调节。体细胞生长、衰老和寿命还受到多种激素和营养信号的影响，要回答为什么较小个体可能更长寿这个问题，还需要做大量工作。
