摘要：The evolutionarily conserved TOR (Target of Rapamycin) signaling controls growth and metabolism from yeast to mammals [1]. Mammalian or mechanistic TOR (mTOR) plays the key role in aging and age-related disease [2]. Rapamycin, a drug used clinically for organ transplants, coronary stent coating and certain forms of cancer treatments, is an inhibitor for mTOR. In the first robust demonstration of pharmacologically-induced life extension in a mammal, rapamycin increased longevity of mice via either feeding or injection [2]. However, rapamycin treatment also showed the detrimental metabolic effects, including hyperinsulinemia, hyperlipidemia, glucose intolerance and insulin resistance. Those observations present a paradox of improved survival despite metabolic impairments. How rapamycin extended lifespan with such paradoxical metabolic effects remains to be elucidated [3]. In the various studies of rapamycin treatment, length of rapamycin treatment varied from two weeks to two years. With short-term rapamycin treatment, mice showed the detrimental metabolic effects, while a much longer length (up to 1.5 to 2 years) of rapamycin treatment led to increased longevity. Duration of rapamycin treatment may be one of the key factors that determine outcomes of the treatment. Longer-term rapamycin treatment may cause beneficial metabolic "switch" that is associated with enhanced insulin signaling and extended longevity
