代谢通路在衰老过程中的关键作用.pdf

PERSPECTIVES IN DIABETES The Critical Role of Metabolic Pathways in Aging Nir Barzilai,1,2,3 Derek M. Huffman,1,3 Radhika H. Muzumdar,1,3,4,5 and Andrzej Bartke6,7 Aging is characterized by a deterioration in the maintenance of and secretion of proinflammatory cytokines by increasing homeostatic processes over time, leading to functional decline numbers of senescent cells (4). Collectively, these age- and increased risk for disease and death. The aging process is related alterations in metabolism and body fat distribu- characterized metabolically by insulin resistance, changes in tion are active participants in a vicious cycle that can body composition, and physiological declines in growth hormone accelerate the aging process and the onset of disease. (GH), insulin-like growth factor-1 (IGF-1), and sex steroids. Some Body composition changes and aging. In humans, in- interventions designed to address features of aging, such as creased adiposity typically develops between the third and caloric restriction or visceral fat depletion, have succeeded in seventh decades of life and may increase, decrease, or improving insulin action and life span in rodents. Meanwhile, pharmacologic interventions and hormonal perturbations have remain unchanged thereafter. Computational tomography increased the life span of several mammalian species without scans in men and women reveal that as age increases, necessarily addressing features of age-related metabolic decline. subcutaneous fat (SF) decreases, whereas VF, which is the These interventions include inhibition of the mammalian target of sum of fat depots inside the abdominal cavity, increases (3). rapamycin and lifetime deficiency in GH/IGF-1 signaling. However, VF a