Correspondence: Isao Shimokawa, MD, PhD, Department of Pathology, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki City 852-8523, Japan. Phone: +81-95-849-7050 or 7051. Fax: +81-95-849-7052. e-mail: shimo@net.nagasaki-u.ac.jp

Abstract: Evolutional theories of aging and caloric restriction (CR) in animals predict the presence of neuroendocrine signals to divert the limited energy resources from energy-costly physiologic processes such as reproduction to those essential for survival in response to food shortage. The diversion of energy and subsequent molecular mechanisms might extend the lifespan. A growing body of evidence indicates that leptin, a peptide hormone secreted from adipocytes, has a key role in neuroendocrine adaptation against life-threatening stress such as fasting. The present review discusses the potential role of leptin in the anti-aging action of CR. Although several alternative signaling pathways might also mediate the anti-aging action of CR, leptin signaling could be a substantial pathway in the CR action. Research on neuroendocrine mechanisms of CR is warranted, because such efforts might provide clues to the regulation of the aging process in humans.

Key Words: Leptin, nutrition, caloric restriction, elderly, neuroendocrinology, aging