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Targeting mTOR signaling to promote healthy longevity
Author(s) -
Kaeberlein Matt
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.256.4
Subject(s) - pi3k/akt/mtor pathway , longevity , mechanistic target of rapamycin , life expectancy , medicine , sirolimus , autophagy , pharmacology , physiology , biology , signal transduction , gerontology , microbiology and biotechnology , apoptosis , population , biochemistry , environmental health
The FDA approved drug rapamycin is a specific inhibitor of mTOR that increases lifespan and healthspan in rodents. Nevertheless, important questions exist regarding the translational potential of rapamycin and other mTOR inhibitors for human aging, and the optimal dose, duration, and mechanisms of action remain to be determined. Here I will report on the effects of short‐term treatment with rapamycin in middle‐aged mice and companion dogs. We find that transient treatment with rapamycin is sufficient to increase life expectancy by more than 50% and improve measures of healthspan in middle‐aged mice. This treatment is associated with a remodelling of the gut microbiome and a dramatic shift in the cancer spectrum of female mice. In dogs, we have defined a dose of rapamycin that is well tolerated, and initial results are consistent with improvements in age‐associated cardiac function. These data suggest that a transient treatment with rapamycin may yield robust health benefits in mice, dogs, and perhaps humans.