Rapamycin, But Not Resveratrol or Simvastatin, Extends Life Span of Genetically Heterogeneous Mice

被引：693

作者：

Miller, Richard A. ^{[1
,2
,3
]}

Harrison, David E. ^{[4
]}

Astle, C. M. ^{[4
]}

Baur, Joseph A. ^{[5
,6
]}

Boyd, Angela Rodriguez ^{[7
]}

de Cabo, Rafael ^{[8
]}

Fernandez, Elizabeth ^{[9
,10
]}

Flurkey, Kevin ^{[4
]}

Javors, Martin A. ^{[9
,10
]}

Nelson, James F. ^{[9
,10
]}

Orihuela, Carlos J. ^{[7
]}

Pletcher, Scott ^{[2
,11
]}

Sharp, Zelton Dave ^{[12
,13
]}

Sinclair, David ^{[14
]}

Starnes, Joseph W. ^{[15
]}

Wilkinson, J. Erby ^{[16
]}

Nadon, Nancy L. ^{[17
]}

Strong, Randy ^{[10
,18
,19
,20
]}

机构：

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

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

[3] Ann Arbor VA Med Ctr, Grad Res Educ & Clin Ctr, Ann Arbor, MI USA

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

[5] Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA

[6] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA

[7] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA

[8] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA

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

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

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

[12] Univ Texas Hlth Sci Ctr San Antonio, Inst Biotechnol, San Antonio, TX 78229 USA

[13] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA

[14] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[15] Univ N Carolina, Dept Kinesiol, Greensboro, NC 27412 USA

[16] Univ Michigan, Sch Med, Unit Lab Anim Med, Ann Arbor, MI USA

[17] NIA, Biol Aging Program, Bethesda, MD 20892 USA

[18] Univ Texas Hlth Sci Ctr San Antonio, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA

[19] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78229 USA

[20] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA

来源：

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES | 2011年 / 66卷 / 02期

基金：

美国国家卫生研究院;

关键词：

TOR; Rapamycin; Life span; Resveratrol; CANCER-THERAPY; C-ELEGANS; DROSOPHILA-MELANOGASTER; CAENORHABDITIS-ELEGANS; REDUCTASE INHIBITOR; DIETARY RESTRICTION; ENDOTHELIAL-CELLS; SIGNALING PATHWAY; DWARF MICE; MTOR;

D O I：

10.1093/gerona/glq178

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

030301 [社会学]; 100201 [内科学];

摘要：

Rapamycin was administered in food to genetically heterogeneous mice from the age of 9 months and produced significant increases in life span, including maximum life span, at each of three test sites. Median survival was extended by an average of 10% in males and 18% in females. Rapamycin attenuated age-associated decline in spontaneous activity in males but not in females. Causes of death were similar in control and rapamycin-treated mice. Resveratrol (at 300 and 1200 ppm food) and simvastatin (12 and 120 ppm) did not have significant effects on survival in male or female mice. Further evaluation of rapamycin's effects on mice is likely to help delineate the role of the mammalian target of rapamycin complexes in the regulation of aging rate and age-dependent diseases and may help to guide a search for drugs that retard some or all of the diseases of aging.

引用

页码：191 / 201

页数：11

共 51 条

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HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes [J].