Rapamycin slows aging in mice

被引:504
作者
Wilkinson, John E. [1 ,3 ]
Burmeister, Lisa [1 ,2 ]
Brooks, Susan V. [4 ]
Chan, Chi-Chao [5 ]
Friedline, Sabrina [1 ,2 ]
Harrison, David E. [6 ]
Hejtmancik, James F. [7 ]
Nadon, Nancy [8 ]
Strong, Randy [10 ,11 ,12 ,13 ]
Wood, Lauren K. [4 ]
Woodward, Maria A. [9 ]
Miller, Richard A. [1 ,2 ]
机构
[1] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Unit Lab Anim Med, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Dept Mol & Integrat Physiol & Biomed Engn, Ann Arbor, MI 48109 USA
[5] NEI, Histol Core, NIH, Bethesda, MD 20892 USA
[6] Jackson Lab, Bar Harbor, ME 04609 USA
[7] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA
[8] NIA, Div Aging Biol, Bethesda, MD 20892 USA
[9] Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol, Ann Arbor, MI 48105 USA
[10] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA
[11] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA
[12] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78229 USA
[13] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA
关键词
interventions; longevity pathology; TOR; LIFE-SPAN EXTENSION; AMES DWARF MICE; CELL-CYCLE; TOR; PATHWAY; TARGET; CANCER; RESTRICTION; METABOLISM; FERTILITY;
D O I
10.1111/j.1474-9726.2012.00832.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Rapamycin increases lifespan in mice, but whether this represents merely inhibition of lethal neoplastic diseases, or an overall slowing in multiple aspects of aging is currently unclear. We report here that many forms of age-dependent change, including alterations in heart, liver, adrenal glands, endometrium, and tendon, as well as age-dependent decline in spontaneous activity, occur more slowly in rapamycin-treated mice, suggesting strongly that rapamycin retards multiple aspects of aging in mice, in addition to any beneficial effects it may have on neoplastic disease. We also note, however, that mice treated with rapamycin starting at 9 months of age have significantly higher incidence of testicular degeneration and cataracts; harmful effects of this kind will guide further studies on timing, dosage, and tissue-specific actions of rapamycin relevant to the development of clinically useful inhibitors of TOR action.
引用
收藏
页码:675 / 682
页数:8
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