Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction

被引：425

作者：

Miller, Richard A. ^{[1
,2
]}

Harrison, David E. ^{[3
]}

Astle, Clinton M. ^{[3
]}

Fernandez, Elizabeth ^{[4
,5
]}

Flurkey, Kevin ^{[3
]}

Han, Melissa ^{[1
,2
]}

Javors, Martin A. ^{[6
]}

Li, Xinna ^{[1
,2
]}

Nadon, Nancy L. ^{[7
]}

Nelson, James F. ^{[8
,9
]}

Pletcher, Scott ^{[2
,10
]}

Salmon, Adam B. ^{[9
]}

Sharp, Zelton Dave ^{[9
,11
]}

Van Roekel, Sabrina ^{[1
,2
]}

Winkleman, Lynn ^{[1
,2
]}

Strong, Randy ^{[4
,5
,9
]}

机构：

[1] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA

[3] Jackson Lab, Bar Harbor, ME 04609 USA

[4] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA

[5] South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78229 USA

[6] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA

[7] NIA, Div Aging Biol, Bethesda, MD 20892 USA

[8] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA

[9] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA

[10] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA

[11] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78245 USA

来源：

AGING CELL | 2014年 / 13卷 / 03期

关键词：

aging; caloric restriction; glucose; IGF-1; insulin; longevity; mouse; mTOR; rapamycin; xenobiotic metabolism; GENETICALLY HETEROGENEOUS MICE; INTERVENTIONS TESTING PROGRAM; AMES DWARF MICE; INSULIN SENSITIVITY; EXTENSION; LONGEVITY; TOR; RESISTANCE; PATHWAY; GENES;

D O I：

10.1111/acel.12194

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Rapamycin, an inhibitor of mTOR kinase, increased median lifespan of genetically heterogeneous mice by 23% (males) to 26% (females) when tested at a dose threefold higher than that used in our previous studies; maximal longevity was also increased in both sexes. Rapamycin increased lifespan more in females than in males at each dose evaluated, perhaps reflecting sexual dimorphism in blood levels of this drug. Some of the endocrine and metabolic changes seen in diet-restricted mice are not seen in mice exposed to rapamycin, and the pattern of expression of hepatic genes involved in xenobiotic metabolism is also quite distinct in rapamycin-treated and diet-restricted mice, suggesting that these two interventions for extending mouse lifespan differ in many respects.

引用

页码：468 / 477

页数：10

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