Editors' ChoiceAging

Elixi-TOR of Life?

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Science Signaling  21 Jul 2009:
Vol. 2, Issue 80, pp. ec244
DOI: 10.1126/scisignal.280ec244

The mammalian target of rapamycin (mTOR) is an important regulator of cellular responses to nutrient availability, growth factors, and stress. Noting that inhibition of mTOR signaling is associated with increased life span in invertebrates, Harrison et al. analyzed the effects of dietary rapamycin, an inhibitor of mTOR complex 1, on the life spans of three cohorts of genetically heterogeneous mice. The authors found that rapamycin increased both the median and maximum life spans of treated mice compared with those of control mice. These effects were observed even though the mice were 600 days old at the time that the treatment was initiated, an age equivalent to that of a 60-year-old person. Both female and male mice showed improved life span when fed rapamycin, although the effects were greater for females. Biochemical analyses showed that the abundance of phosphorylated ribosomal subunit protein S6, a downstream target of mTOR signaling, was lower in rapamycin-treated mice than in control mice. A separate cohort of mice that were 270 days old when they started being fed rapamycin have also exhibited increased survival compared with control mice. As Kaeberlein and Kennedy point out, the potent immunosuppressive effects of rapamycin preclude its use by humans as an antiaging drug; however, this study suggests that careful targeting of mTOR signaling may provide an effective therapy against age-related diseases.

D. E. Harrison, R. Strong, Z. D. Sharp, J. F. Nelson, C. M. Astle, K. Flurkey, N. L. Nadon, J. E. Wilkinson, K. Frenkel, C. S. Carter, M. Pahor, M. A. Javors, E. Fernandez, R. A. Miller, Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460, 392–395 (2009). [PubMed]

M. Kaeberlein, B. K. Kennedy, A midlife longevity drug? Nature 460, 331–332 (2009). [PubMed]

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