Leptin signaling and aging: insight from caloric restriction.
Organisms have evolved neuroendocrine and metabolic response systems to enhance survival during periods of food shortage, which occur frequently in nature. The anti-aging effect of caloric restriction (CR) might derive from these adaptive responses to maximize organism survival. The present article discusses the potential role for leptin, a hormone secreted from adipocytes, as a key signal that induces the adaptive responses relevant to CR. Evidence indicates that a CR-induced reduction of the plasma leptin concentration suppresses the gonadal, somatotropic, and thyroidal axes, and activates the adrenal axis. Metabolic adaptation, a shift in fuel utilization mainly conducted in the liver, seems to require leptin signaling. Although alternative signaling pathways might also mediate the anti-aging effects of CR, leptin signaling could be a substantial pathway involved in these effects. Molecular dissection of the mechanisms underlying the effects of CR will contribute to a better understanding of the aging process, leading to the extension of a healthy lifespan in humans.
Shimokawa
I
I
Department of Pathology, Nagasaki University School of Medicine, 1-12-4 Sakamoto, 852-8523, Nagasaki, Japan. shimo@net.nagasaki-u.ac.jp
Higami
Y
Y
D000222:Adaptation, Physiological; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002149:Energy Intake / Q000502:physiology*; D006801:Humans; D020738:Leptin / Q000378:metabolism / Q000502:physiology*; D009490:Neurosecretory Systems / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D020738:Leptin