The Hallmarks of Aging

被引：10861

作者：

Lopez-Otin, Carlos ^{[1
]}

Blasco, Maria A. ^{[2
]}

Partridge, Linda ^{[3
,4
]}

Serrano, Manuel ^{[5
]}

Kroemer, Guido ^{[6
,7
,8
,9
,10
]}

机构：

[1] Univ Oviedo, Dept Bioquim & Biol Mol, Inst Univ Oncol IUOPA, Oviedo, Spain

[2] Spanish Natl Canc Res Ctr CNIO, Mol Oncol Program, Telomeres & Telomerase Grp, Madrid, Spain

[3] Max Planck Inst Biol Ageing, Cologne, Germany

[4] UCL, Inst Hlth Aging, Dept Genet Evolut & Environm, London, England

[5] Spanish Natl Canc Res Ctr CNIO, Mol Oncol Program, Tumor Suppress Grp, Madrid, Spain

[6] U848, INSERM, Villejuif, France

[7] Inst Gustave Roussy, Metabol & Cell Biol Platforms, Villejuif, France

[8] Ctr Rech Cordeliers, Paris, France

[9] Hop Europeen Georges Pompidou, Pole Biol, AP HP, Paris, France

[10] Univ Paris 05, Sorbonne Paris Cite, Paris, France

来源：

CELL | 2013年 / 153卷 / 06期

基金：

英国惠康基金;

关键词：

DNA-DAMAGE-RESPONSE; NF-KAPPA-B; LIFE-SPAN EXTENSION; DETECTABLE CLONAL MOSAICISM; DEPENDENT GENE-EXPRESSION; C; ELEGANS; STEM-CELLS; CELLULAR SENESCENCE; OXIDATIVE STRESS; TELOMERE LENGTH;

D O I：

10.1016/j.cell.2013.05.039

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：

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects.

引用

页码：1194 / 1217

页数：24

共 296 条

[1] Motif module map reveals enforcement of aging by continual NF-κB activity [J].

Adler, Adam S. ;

Sinha, Saurabh ;

Kawahara, Tiara L. A. ;

Zhang, Jennifer Y. ;

Segal, Eran ;

Chang, Howard Y. .

GENES & DEVELOPMENT, 2007, 21 (24) :3244-3257

[2] Somatic Progenitor Cell Vulnerability to Mitochondrial DNA Mutagenesis Underlies Progeroid Phenotypes in Polg Mutator Mice [J].

Ahlqvist, Kati J. ;

Hamalainen, Riikka H. ;

Yatsuga, Shuichi ;

Uutela, Marko ;

Terzioglu, Mugen ;

Gotz, Alexandra ;

Forsstrom, Saara ;

Salven, Petri ;

Angers-Loustau, Alexandre ;

Kopra, Outi H. ;

Tyynismaa, Henna ;

Larsson, Nils-Goran ;

Wartiovaara, Kirmo ;

Prolla, Tomas ;

Trifunovic, Aleksandra ;

Suomalainen, Anu .

CELL METABOLISM, 2012, 15 (01) :100-109

[3] Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan [J].

Alavez, Silvestre ;

Vantipalli, Maithili C. ;

Zucker, David J. S. ;

Klang, Ida M. ;

Lithgow, Gordon J. .

NATURE, 2011, 472 (7342) :226-229

[4] Role of AMPK-mTOR-Ulk1/2 in the Regulation of Autophagy: Cross Talk, Shortcuts, and Feedbacks [J].

Alers, Sebastian ;

Loeffler, Antje S. ;

Wesselborg, Sebastian ;

Stork, Bjoern .

MOLECULAR AND CELLULAR BIOLOGY, 2012, 32 (01) :2-11

[5] Ultra-Deep Sequencing of Mouse Mitochondrial DNA: Mutational Patterns and Their Origins [J].

Ameur, Adam ;

Stewart, James B. ;

Freyer, Christoph ;

Hagstrom, Erik ;

Ingman, Max ;

Larsson, Nils-Goran ;

Gyllensten, Ulf .

PLOS GENETICS, 2011, 7 (03)

[6] If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice [J].

Anisimov, Vladimir N. ;

Berstein, Lev M. ;

Popovich, Irina G. ;

Zabezhinski, Mark A. ;

Egormin, Peter A. ;

Piskunova, Tatiana S. ;

Semenchenko, Anna V. ;

Tyndyk, Margarita L. ;

Yurova, Maria N. ;

Kovalenko, Irina G. ;

Poroshina, Tatiana E. .

AGING-US, 2011, 3 (02) :148-157

[7] The telomere syndromes [J].

Armanios, Mary ;

Blackburn, Elizabeth H. .

NATURE REVIEWS GENETICS, 2012, 13 (10) :693-704

[8] Short Telomeres are Sufficient to Cause the Degenerative Defects Associated with Aging [J].

Armanios, Mary ;

Alder, Jonathan K. ;

Parry, Erin M. ;

Karim, Baktiar ;

Strong, Margaret A. ;

Greider, Carol W. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 85 (06) :823-832

[9] Increased cell-to-cell variation in gene expression in ageing mouse heart [J].

Bahar, Rumana ;

Hartmann, Claudia H. ;

Rodriguez, Karl A. ;

Denny, Ashley D. ;

Busuttil, Rita A. ;

Dolle, Martijn E. T. ;

Calder, R. Brent ;

Chisholm, Gary B. ;

Pollock, Brad H. ;

Klein, Christoph A. ;

Vijg, Jan .

NATURE, 2006, 441 (7096) :1011-1014

[10] Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan [J].

Baker, Darren J. ;

Dawlaty, Meelad M. ;

Wijshake, Tobias ;

Jeganathan, Karthik B. ;

Malureanu, Liviu ;

van Ree, Janine H. ;

Crespo-Diaz, Ruben ;

Reyes, Santiago ;

Seaburg, Lauren ;

Shapiro, Virginia ;

Behfar, Atta ;

Terzic, Andre ;

van de Sluis, Bart ;

van Deursen, Jan M. .

NATURE CELL BIOLOGY, 2013, 15 (01) :96-U208

← 1 2 3 4 5 6 7 8 9 10 →