in a Japanese concentration camp as a criterion of age. J Gerontol. 1948; 3(1):14–17.
9 9 Schrödinger E. What Is Life? The Physical Aspect of the Living Cell; With Mind and Matter; & Autobiographical Sketches. Cambridge University Press; 1992
10 10 Medawar P. An unsolved problem of biology. University College, London; 1952.
11 11 Williams GC. Pleiotropy, natural selection, and the evolution of senescence. Evolution. 1957; 11(4):398–411.
12 12 Hamilton WD. The moulding of senescence by natural selection. J Theor Biol. 1966; 12(1):12–45.
13 13 Charlesworth B. Evolution in Age‐Structured Populations, Cambridge University Press; 1994.
14 14 Kirkwood TB. Evolution of ageing. Nature. 1977; 270(5635):301–304.
15 15 López‐Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013; 153(6):1194–1217.
16 16 Kennedy BK, Berger SL, Brunet A, et al. Geroscience: linking aging to chronic disease. Cell 2014; 159(4):709–713.
17 17 Hoeijmakers JH. DNA damage, aging, and cancer. N Engl J Med. 2019; 361(15):1475–1485.
18 18 Moskalev AA, Shaposhnikov MV, Plyusnina EN, et al. The role of DNA damage and repair in aging through the prism of Koch‐like criteria. Ageing Res Rev. 2013; 12(2):661–684.
19 19 Park CB, Larsson N‐G. Mitochondrial DNA mutations in disease and aging. J Cell Biol. 2011; 193(5):809–818.
20 20 Baker DJ, Dawlaty MM, Wijshake T, et al. Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan. Nat Cell Biol. 2013; 15(1):96–102.
21 21 Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961; 25(3):585–621.
22 22 Blasco MA. Telomere length, stem cells and aging. Nat Chem Biol. 2007; 3(10):640–649.
23 23 Armanios M, Alder JK, Parry EM, Karim B, Strong MA, Greider CW. Short telomeres are sufficient to cause the degenerative defects associated with aging. Am J Hum Genet. 2009; 85(6):823–832.
24 24 Tomás‐Loba A, Flores I, Fernández‐Marcos PJ, et al. Telomerase reverse transcriptase delays aging in cancer‐resistant mice. Cell 2008; 135(4):609–622.
25 25 Wang Q, Zhan Y, Pedersen NL, Fang F, Hägg S. Telomere length and all‐cause mortality: a meta‐analysis. Ageing Res Rev. 2018; 48:11–20.
26 26 Blackburn EH, Epel ES, Lin J. Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection. Science. 2015; 350(6265):1193–1198.
27 27 Ferrucci L, Gonzalez‐Freire M, Fabbri E, et al. Measuring biological aging in humans: A quest. Aging Cell. 2019; 19(2):e13080.
28 28 Hannum G, Guinney J, Zhao L, et al. Genome‐wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013; 49(2):359–367.
29 29 Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013; 14(10):3156.
30 30 Marioni RE, Shah S, McRae AF, et al. The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936. Int J Epidemiol. 2015; 44(4):1388–1396.
31 31 Marioni RE, Shah S, McRae AF, et al. DNA methylation age of blood predicts all‐cause mortality in later life. Genome Biol. 2015; 16:25.
32 32 Horvath S, Raj K. DNA methylation‐based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet. 2018; 19(6):371–384.
33 33 Field AE, Robertson NA, Wang T, Havas A, Ideker T, Adams PD. DNA methylation clocks in aging: categories, causes, and consequences. Mol Cell. 2018; 71(6):882–895.
34 34 Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956; 11(3):298–300.
35 35 Hekimi S, Lapointe J, Wen Y. Taking a ‘good’ look at free radicals in the aging process. Trends Cell Biol. 2011; 21(10):569–576.
36 36 Zane AC, Reiter DA, Shardell M, et al. Muscle strength mediates the relationship between mitochondrial energetics and walking performance. Aging Cell. 2017; 16(3):461–468.
37 37 Powers ET, Morimoto RI, Dillin A, Kelly JW, Balch WE. Biological and chemical approaches to diseases of proteostasis deficiency. Annu Rev Biochem. 2009; 78:959–991.
38 38 Koga H, Kaushik S, Cuervo AM. Protein homeostasis and aging: The importance of exquisite quality control. Ageing Res Rev. 2011; 10(2):205–215.
39 39 Min J‐N, Whaley RA, Sharpless NE, Lockyer P, Portbury AL, Patterson C. CHIP deficiency decreases longevity, with accelerated aging phenotypes accompanied by altered protein quality control. Mol Cell Biol. 2008; 28(12):4018–4025.
40 40 Hansen M, Rubinsztein DC, Walker DW. Autophagy as a promoter of longevity: insights from model organisms. Nat Rev Mol Cell Biol. 2018; 19(9):579–593.
41 41 Barzilai N, Huffman DM, Muzumdar RH, Bartke A. The critical role of metabolic pathways in aging. Diabetes. 2012; 61(6):1315–1322.
42 42 Singh PP, Demmitt BA, Nath RD, Brunet A. The genetics of aging: a vertebrate perspective. Cell. 2019; 177(1):200–220.
43 43 Garinis GA, van der Horst GTJ, Vijg J, Hoeijmakers JHJ. DNA damage and ageing: new‐age ideas for an age‐old problem. Nat Cell Biol. 2008; 10(11):1241–1247.
44 44 Fontana L, Partridge L, Longo VD.Extending healthy life span – from yeast to humans. Science. 2010; 328(5976):321–326.
45 45 Harrison DE, Strong R, Sharp ZD, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009; 460(7253):392–395.
46 46 Justice JN, Ferrucci L, Newman AB, et al.A framework for selection of blood‐based biomarkers for geroscience‐guided clinical trials: report from the TAME Biomarkers Workgroup. GeroScience. 2018; 40(5–6):419–436.
47 47 Coppé J‐P, Desprez P‐Y, Krtolica A, Campisi J. The senescence‐associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010; 5:99–118.
48 48 van Deursen JM. The role of senescent cells in ageing. Nature. 2014; 509(7501):439–446.
49 49 Collado M, Blasco MA, Serrano M. Cellular senescence in cancer and aging. Cell. 2007; 130(2):223–233.
50 50 Krishnamurthy J, Torrice C, Ramsey MR, et al. Ink4a/Arf expression is a biomarker of aging. J Clin Invest. 2004; 114(9):1299–1307.
51 51 Ressler S, Bartkova J, Niederegger H, et al. p16INK4A is a robust in vivo biomarker of cellular aging in human skin. Aging Cell. 2006; 5(5):379–389.
52 52 Jeck WR, Siebold AP, Sharpless NE. Review: a meta‐analysis of GWAS and age‐associated diseases. Aging Cell. 2012; 11(5):727–731.
53 53 Justice JN, Gregory H, Tchkonia T, et al. Cellular senescence biomarker p16INK4a+ cell burden in thigh adipose is associated with poor physical function in older women. J Gerontol Ser A. 2017; 73(7):939–945.
54 54 Matheu A, Maraver A, Klatt P, et al. Delayed ageing through damage protection by the Arf/p53 pathway. Nature. 2007; 448(7151):375–379.
55 55 Matheu A, Maraver A, Collado M, et al. Anti‐aging activity of the Ink4/Arf locus. Aging Cell. 2009; 8(2):152–161.
56 56 Baker DJ, Wijshake T, Tchkonia T, et al. Clearance of p16Ink4a‐positive senescent cells delays ageing‐associated disorders. Nature. 2011; 479(7372):232–236.
57 57 Baker DJ, Childs BG, Durik M, et al. Naturally occurring p16(Ink4a)‐positive cells shorten healthy lifespan. Nature. 2016; 530(7589):184–189.
58 58 van Deursen JM. Senolytic therapies for healthy longevity. Science. 2019; 364(6441):636–637.
59 59 Sahin E, Depinho RA. Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature. 2010; 464(7288):520–528.
60 60 Lavasani M, Robinson AR, Lu A, et al. Muscle‐derived stem/progenitor