期刊
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
卷 71, 期 7, 页码 841-849出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glw090
关键词
Intermittent rapamycin; Lifespan; Mouse; Rapamycin analogs
资金
- National Institute on Aging at the National Institutes of Health [R00 AG041765]
- University of Wisconsin-Madison School of Medicine and Public Health
- University of Wisconsin-Madison Department of Medicine
- American Diabetes Association [1-16-PMF-001]
- Glenn Award for Research in the Biological Mechanisms of Aging
- AFAR Research Grant from American Federation for Aging Research
- William S. Middleton Memorial Veterans Hospital
Rapamycin (sirolimus) is a macrolide immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR) protein kinase and extends lifespan in model organisms including mice. Although rapamycin is an FDA-approved drug for select indications, a diverse set of negative side effects may preclude its wide-scale deployment as an antiaging therapy. mTOR forms two different protein complexes, mTORC1 and mTORC2; the former is acutely sensitive to rapamycin whereas the latter is only chronically sensitive to rapamycin in vivo. Over the past decade, it has become clear that although genetic and pharmacological inhibition of mTORC1 extends lifespan and delays aging, inhibition of mTORC2 has negative effects on mammalian health and longevity and is responsible for many of the negative side effects of rapamycin. In this review, we discuss recent advances in understanding the molecular and physiological effects of rapamycin treatment, and we discuss how the use of alternative rapamycin treatment regimens or rapamycin analogs has the potential to mitigate the deleterious side effects of rapamycin treatment by more specifically targeting mTORC1. Although the side effects of rapamycin are still of significant concern, rapid progress is being made in realizing the revolutionary potential of rapamycin-based therapies for the treatment of diseases of aging.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据