Hallmarks of aging: An expanding universe

被引:2649
作者
Lopez-Otin, Carlos [1 ,2 ,3 ]
Blasco, Maria A. [4 ]
Partridge, Linda [5 ,6 ]
Serrano, Manuel [7 ,8 ,9 ]
Kroemer, Guido [10 ,11 ,12 ]
机构
[1] Univ Oviedo, Inst Univ Oncol IUOPA, Dept Bioquim & Biol Mol, Oviedo, Spain
[2] Inst Invest Sanitaria Principado Asturias ISPA, Oviedo, Spain
[3] Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
[4] Spanish Natl Canc Ctr CNIO, Mol Oncol Program, Telomeres & Telomerase Grp, Madrid, Spain
[5] UCL, Inst Hlth Ageing, Dept Genet Evolut & Environm, London, England
[6] Max Planck Inst Biol Ageing, Cologne, Germany
[7] Barcelona Inst Sci & Technol BIST, Inst Res Biomed IRB Barcelona, Barcelona, Spain
[8] Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain
[9] Altos Labs, Cambridge, England
[10] Sorbonne Univ, Ctr Rech Cordeliers, Equipe Labellisee Ligue Canc, Univ Paris,INSERM U1138,Inst Univ France, Paris, France
[11] Gustave Roussy, Metabol & Cell Biol Platforms, Villejuif, France
[12] Hop Europeen Georges Pompidou, AP HP, Inst Canc Paris CARPEM, Dept Biol, Paris, France
基金
欧洲研究理事会; 英国生物技术与生命科学研究理事会; 欧盟地平线“2020”;
关键词
ADULT STEM-CELLS; GUT MICROBIOTA; LIFE-SPAN; CALORIC RESTRICTION; SOMATIC MUTATION; SENESCENT CELLS; AGE; DISEASE; AUTOPHAGY; SURVIVAL;
D O I
10.1016/j.cell.2022.11.001
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 driven by hallmarks fulfilling the following three premises: (1) their age-associated manifestation, (2) the acceleration of aging by experimentally accentuating them, and (3) the opportunity to decelerate, stop, or reverse aging by therapeutic interventions on them. We propose the following twelve hallmarks of aging: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautoph-agy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These hallmarks are intercon-nected among each other, as well as to the recently proposed hallmarks of health, which include organiza-tional features of spatial compartmentalization, maintenance of homeostasis, and adequate responses to stress.
引用
收藏
页码:243 / 278
页数:36
相关论文
共 300 条
[81]   Strategies for late phase preclinical and early clinical trials of senolytics [J].
Gerdes, Erin O. Wissler ;
Misra, Avanish ;
Netto, Jair Machado Espindola ;
Tchkonia, Tamar ;
Kirkland, James L. .
MECHANISMS OF AGEING AND DEVELOPMENT, 2021, 200
[82]   Adjusting for age improves identification of gut microbiome alterations in multiple diseases [J].
Ghosh, Tarini S. ;
Das, Mrinmoy ;
Jeffery, Ian B. ;
O'Toole, Paul W. .
ELIFE, 2020, 9
[83]   The gut microbiome as a modulator of healthy ageing [J].
Ghosh, Tarini Shankar ;
Shanahan, Fergus ;
O'Toole, Paul W. .
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2022, 19 (09) :565-584
[84]   Multi-omic rejuvenation of human cells by maturation phase transient reprogramming [J].
Gill, Diljeet ;
Parry, Aled ;
Santos, Fatima ;
Okkenhaug, Hanneke ;
Todd, Christopher D. ;
Hernando-Herraez, Irene ;
Stubbs, Thomas M. ;
Milagre, Ines ;
Reik, Wolf .
ELIFE, 2022, 11
[85]   A Disease or Not a Disease? Aging As a Pathology [J].
Gladyshev, Timothy V. ;
Gladyshev, Vadim N. .
TRENDS IN MOLECULAR MEDICINE, 2016, 22 (12) :995-996
[86]   Molecular damage in aging [J].
Gladyshev, Vadim N. ;
Kritchevsky, Stephen B. ;
Clarke, Steven G. ;
Cuervo, Ana Maria ;
Fiehn, Oliver ;
de Magalhaes, Joao Pedro ;
Mau, Theresa ;
Maes, Michal ;
Moritz, Robert L. ;
Niedernhofer, Laura J. ;
Van Schaftingen, Emile ;
Tranah, Gregory J. ;
Walsh, Kenneth ;
Yura, Yoshimitsu ;
Zhang, Bohan ;
Cummings, Steven R. .
NATURE AGING, 2021, 1 (12) :1096-1106
[87]   Protective Role of Spermidine in Colitis and Colon Carcinogenesis [J].
Gobert, Alain P. ;
Latour, Yvonne L. ;
Asim, Mohammad ;
Barry, Daniel P. ;
Allaman, Margaret M. ;
Finley, Jordan L. ;
Smith, Thaddeus M. ;
McNamara, Kara M. ;
Singh, Kshipra ;
Sierra, Johanna C. ;
Delgado, Alberto G. ;
Luis, Paula B. ;
Schneider, Claus ;
Washington, M. Kay ;
Piazuelo, M. Blanca ;
Zhao, Shilin ;
Coburn, Lori A. ;
Wilson, Keith T. .
GASTROENTEROLOGY, 2022, 162 (03) :813-+
[88]   Etanercept improves aging-induced cognitive deficits by reducing inflammation and vascular dysfunction in rats [J].
Gocmez, Semil Selcen ;
Yazir, Yusufhan ;
Gacar, Gulcin ;
Sahin, Tugce Demirtas ;
Arkan, Sertan ;
Karson, Ayse ;
Utkan, Tijen .
PHYSIOLOGY & BEHAVIOR, 2020, 224
[89]   Sex- and strain-specific effects of mitochondrial uncoupling on age-related metabolic diseases in high-fat diet-fed mice [J].
Goedeke, Leigh ;
Murt, Kelsey N. ;
Di Francesco, Andrea ;
Camporez, Joao Paulo ;
Nasiri, Ali R. ;
Wang, Yongliang ;
Zhang, Xian-Man ;
Cline, Gary W. ;
de Cabo, Rafael ;
Shulman, Gerald, I .
AGING CELL, 2022, 21 (02)
[90]   Controlled-release mitochondrial protonophore (CRMP) reverses dyslipidemia and hepatic steatosis in dysmetabolic nonhuman primates [J].
Goedeke, Leigh ;
Peng, Liang ;
Montalvo-Romeral, Valle ;
Butrico, Gina M. ;
Dufour, Sylvie ;
Zhang, Xian-Man ;
Perry, Rachel J. ;
Cline, Gary W. ;
Kievit, Paul ;
Chng, Keefe ;
Petersen, Kitt Falk ;
Shulman, Gerald I. .
SCIENCE TRANSLATIONAL MEDICINE, 2019, 11 (512)