The Mitochondrial Basis of Aging

被引：1035

作者：

Sun, Nuo ^{[1
]}

Youle, Richard J. ^{[2
]}

Finkel, Toren ^{[1
]}

机构：

[1] NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA

[2] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA

来源：

MOLECULAR CELL | 2016年 / 61卷 / 05期

关键词：

EXTENDS LIFE-SPAN; SKELETAL-MUSCLE; PYRUVATE-DEHYDROGENASE; DNA MUTATIONS; STEM-CELLS; NLRP3; INFLAMMASOME; PHYSICAL-EXERCISE; OXIDATIVE STRESS; QUALITY-CONTROL; LONGEVITY;

D O I：

10.1016/j.molcel.2016.01.028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A decline inmitochondrial quality and activity has been associated with normal aging and correlated with the development of a wide range of age-related diseases. Here, we review the evidence that a decline in mitochondria function contributes to aging. In particular, we discuss how mitochondria contribute to specific aspects of the aging process, including cellular senescence, chronic inflammation, and the age-dependent decline in stem cell activity. Signaling pathways regulating the mitochondrial unfolded protein response and mitophagy are also reviewed, with particular emphasis placed on how these pathways might, in turn, regulate longevity. Taken together, these observations suggest that mitochondria influence or regulate a number of key aspects of aging and suggest that strategies directed at improving mitochondrial quality and function might have far-reaching beneficial effects.

引用

页码：654 / 666

页数：13

共 137 条

[81] Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection [J].

Pellegrino, Mark W. ;

Nargund, Amrita M. ;

Kirienko, Natalia V. ;

Gillis, Reba ;

Fiorese, Christopher J. ;

Haynes, Cole M. .

NATURE, 2014, 516 (7531) :414-+

[82]

Pernas L., 2015, ANN REV PHYSL

[83] Mitochondrial dysfunction in the elderly: Possible role in insulin resistance [J].

Petersen, KF ;

Befroy, D ;

Dufour, S ;

Dziura, J ;

Ariyan, C ;

Rothman, DL ;

DiPietro, L ;

Cline, GW ;

Shulman, GI .

SCIENCE, 2003, 300 (5622) :1140-1142

[84] Endogenous Parkin Preserves Dopaminergic Substantia Nigral Neurons following Mitochondrial DNA Mutagenic Stress [J].

Pickrell, Alicia M. ;

Huang, Chiu-Hui ;

Kennedy, Scott R. ;

Ordureau, Alban ;

Sideris, Dionisia P. ;

Hoekstra, Jake G. ;

Harper, J. Wade ;

Youle, Richard J. .

NEURON, 2015, 87 (02) :371-381

[85] The Roles of PINK1, Parkin, and Mitochondrial Fidelity in Parkinson's Disease [J].

Pickrell, Alicia M. ;

Youle, Richard J. .

NEURON, 2015, 85 (02) :257-273

[86] STUDIES OF SEQUENCE HETEROGENEITY OF MITOCHONDRIAL-DNA FROM RAT AND MOUSE-TISSUES - EVIDENCE FOR AN INCREASED FREQUENCY OF DELETIONS-ADDITIONS WITH AGING [J].

PIKO, L ;

HOUGHAM, AJ ;

BULPITT, KJ .

MECHANISMS OF AGEING AND DEVELOPMENT, 1988, 43 (03) :279-293

[87] Complex IV-deficient Surf1-/- mice initiate mitochondrial stress responses [J].

Pulliam, Daniel A. ;

Deepa, Sathyaseelan S. ;

Liu, Yuhong ;

Hill, Shauna ;

Lin, Ai-Ling ;

Bhattacharya, Arunabh ;

Shi, Yun ;

Sloane, Lauren ;

Viscomi, Carlo ;

Zeviani, Massimo ;

Van Remmen, Holly .

BIOCHEMICAL JOURNAL, 2014, 462 :359-371

[88] Oncogene-induced senescence results in marked metabolic and bioenergetic alterations [J].

Quijano, Celia ;

Cao, Liu ;

Fergusson, Maria M. ;

Romero, Hector ;

Liu, Jie ;

Gutkind, Sarah ;

Rovira, Ilsa I. ;

Mohney, Robert P. ;

Karoly, Edward D. ;

Finkel, Toren .

CELL CYCLE, 2012, 11 (07) :1383-1392

[89] New roles for mitochondrial proteases in health, ageing and disease [J].

Quiros, Pedro M. ;

Langer, Thomas ;

Lopez-Otin, Carlos .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2015, 16 (06) :345-359

[90] Parkin overexpression during aging reduces proteotoxicity, alters mitochondrial dynamics, and extends lifespan [J].

Rana, Anil ;

Rera, Michael ;

Walker, David W. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (21) :8638-8643

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