CoChat
Sign Up
Cited by 216Cancer survivorship and careFrailty in Older AdultsChildhood Cancer Survivors' Quality of Life

Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors

Open access
Guida, Jennifer L, Ahles, Tim A, Belsky, Daniel, Campisi, Judith, Cohen, Harvey Jay, DeGregori, James, Fuldner, Rebecca, Ferrucci, Luigi +16 more·2019·JNCI: Journal of the National Cancer Institute
DOI 10.1093/jnci/djz136PMC PMC7962788
Open this paper in CoChat — free accountOpen PDF

Abstract

Observational data have shown that some cancer survivors develop chronic conditions like frailty, sarcopenia, cardiac dysfunction, and mild cognitive impairment earlier and/or at a greater burden than similarly aged individuals never diagnosed with cancer or exposed to systemic or targeted cancer therapies. In aggregate, cancer- and treatment-related physical, cognitive, and psychosocial late- and long-term morbidities experienced by cancer survivors are hypothesized to represent accelerated or accentuated aging trajectories. However, conceptual, measurement, and methodological challenges have constrained efforts to identify, predict, and mitigate aging-related consequences of cancer and cancer treatment. In July 2018, the National Cancer Institute convened basic, clinical, and translational science experts for a think tank titled “Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors.” Through the resulting deliberations, several research and resource needs were identified, including longitudinal studies to examine aging trajectories that include detailed data from before, during, and after cancer treatment; mechanistic studies to elucidate the pathways that lead to the emergence of aging phenotypes in cancer survivors; long-term clinical surveillance to monitor survivors for late-emerging effects; and tools to integrate multiple data sources to inform understanding of how cancer and its therapies contribute to the aging process. Addressing these needs will help expand the evidence base and inform strategies to optimize healthy aging of cancer survivors.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/jnci/djz136

Cites

21 of 21 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Senotherapeutic drugs could potentially treat a variety of conditions primarily or secondarily mediated by senescent cell accumulation.

    “The use of senotherapeutic drugs could potentially be effective in treating a variety of conditions primarily or secondarily mediated by accumulation of senescent cells [6, 33, 67–87].”

    From Reducing Senescent Cell Burden in Aging and Disease (2020) · cites this paper as [71]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 126

  1. [1]1. Parry C, Kent EE, Mariotto AB, Alfano CM, Rowland JH. Cancer survivors: a booming population. Cancer Epidemiol Biomarkers Prev . 2011;20(10): 1996-2005.
  2. [2]2. DeSantis CE, Lin CC, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2014. CACancer J Clin . 2014;64(4):252-271.
  3. [4]4. Hurria A, Jones L, Muss HB. Cancer treatment as an accelerated aging process: assessment, biomarkers, and interventions. Am Soc Clin Oncol Educ Book . 2016;35:e516-e522.
  4. [5]5. Armenian SH, Gibson CJ, Rockne RC, Ness KK. Premature aging in young cancer survivors. J Natl Cancer Inst . 2019;111(3):226-232.
  5. [6]6. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell . 2000;100(1):57-70.
  6. [9]9. Gems D, Partridge L. Genetics of longevity in model organisms: debates and paradigm shifts. Annu Rev Physiol . 2013;75(1):621-644.
  7. [10]10. Margolick JB, Ferrucci L. Accelerating aging research: how can we measure the rate of biologic aging? Exp Gerontol . 2015;64:78-80.
  8. [12]12. Ahles TA, Hurria A. New challenges in psycho-oncology research IV: cognition and cancer: conceptual and methodological issues and future directions. Psychooncology . 2018;27(1):1-23.
  9. [13]13. Campisi J, d'Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol . 2007;8(9):729-740.
  10. [15]15. Kim JH, Jenrow KA, Brown SL. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials. Radiat Oncol J . 2014; 32(3):103-115.
  11. [16]16. Watt DG, Horgan PG, McMillan DC. Routine clinical markers of the magnitude of the systemic inflammatory response after elective operation: a systematic review. Surgery . 2015;157(2):362-380.
  12. [18]18. Chang B-D, Swift ME, Shen M, Fang J, Broude EV, Roninson IB. Molecular determinants of terminal growth arrest induced in tumor cells by a chemotherapeutic agent. Proc Natl Acad Sci USA . 2002;99(1):389-394.
  13. [19]19. Schmitt CA, Fridman JS, Yang M, et al. A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell . 2002; 109(3):335-346.
  14. [21]21. Novakova Z, Hubackova S, Kosar M, et al. Cytokine expression and signaling in drug-induced cellular senescence. Oncogene . 2010;29(2):273-284.
  15. [22]22. Buttiglieri S, Ruella M, Risso A, et al. The aging effect of chemotherapy on cultured human mesenchymal stem cells. Exp Hematol . 2011;39(12): 1171-1181.
  16. [23]23. Beeharry N, Broccoli D. Telomere dynamics in response to chemotherapy. Curr Mol Med . 2005;5(2):187-196.
  17. [24]24. Diker-Cohen T, Uziel O, Szyper-Kravitz M, Shapira H, Natur A, Lahav M. The effect of chemotherapy on telomere dynamics: clinical results and possible mechanisms. Leuk Lymphoma . 2013;54(9):2023-2029.
  18. [25]25. Yoon SY, Sung HJ, Park KH, et al. Telomere length shortening of peripheral blood mononuclear cells in solid-cancer patients undergoing standard-dose chemotherapy might be correlated with good treatment response and neutropenia severity. Acta Haematol . 2007;118(1):30-37.
  19. [26]26. Bhakta N, Liu Q, Yeo F, et al. Cumulative burden of cardiovascular morbidity among pediatric, adolescent and young adult Hodgkin lymphoma survivors: an analysis from the St. Jude Lifetime Cohort Study. Lancet Oncol . 2016; 17(9):1325-1334.
  20. [27]27. Ness KK, Armstrong GT, Kundu M, Wilson CL, Tchkonia T, Kirkland JL. Frailty in childhood cancer survivors. Cancer . 2015;121(10):1540-1547.
  21. [28]28. Ness KK, Krull KR, Jones KE, et al. Physiologic frailty as a sign of accelerated aging among adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study. J Clin Oncol . 2013;31(36):4496-4503.
  22. [29]29. Krull KR, Hardy KK, Kahalley LS, Schuitema I, Kesler SR. Neurocognitive outcomes and interventions in long-term survivors of childhood cancer. J Clin Oncol . 2018;36(21):2181-2189.
  23. [30]30. Ness KK, Bhatia S, Baker KS, et al. Performance limitations and participation restrictions among childhood cancer survivors treated with hematopoietic stem cell transplantation: the Bone Marrow Transplant Survivor Study. Arch Pediatr Adolesc Med . 2005;159(8):706-713.
  24. [31]31. Wilson CL, Stratton K, Leisenring WM, et al. Decline in physical activity level in the Childhood Cancer Survivor Study cohort. Cancer Epidemiol Biomarkers Prev . 2014;23(8):1619-1627.
  25. [32]32. Howell CR, Wilson CL, Ehrhardt MJ, et al. Clinical impact of sedentary behaviors in adult survivors of acute lymphoblastic leukemia: a report from the St. Jude Lifetime Cohort study. Cancer . 2018;124(5):1036-1043.
  26. [33]33. Keating NL, Nørredam M, Landrum MB, Huskamp HA, Meara E. Physical and mental health status of older long-term cancer survivors. J Am Geriatr Soc . 2005;53(12):2145-2152.
  27. [34]34. Alfano CM, Peng J, Andridge RR, et al. Inflammatory cytokines and comorbidity development in breast cancer survivors versus noncancer controls: evidence for accelerated aging? J Clin Oncol . 2017;35(2):149-156.
  28. [35]35. Hewitt M, Rowland JH, Yancik R. Cancer survivors in the United States: age, health, and disability. J Gerontol A Biol Sci Med Sci . 2003;58(1): M82-M91.
  29. [36]36. Gresham G, Dy SM, Zipunnikov V, et al. Fatigability and endurance performance in cancer survivors: analyses from the Baltimore Longitudinal Study of Aging. Cancer . 2018;124(6):1279-1287.
  30. [37]37. Wanigatunga A, Gresham G, Martinez-Amezcua P, et al. Contrasting characteristics of daily physical activity in older adults by cancer history. Cancer . 2018;124(24):4692-4699.
  31. [38]38. Ahles TA, Root JC. Cognitive effects of cancer and cancer treatments. Annu Rev Clin Psychol . 2018;14:425-451.
  32. [39]39. Guralnik JM, Melzer D. Chronological and functional ageing. In: Copeland JRM, Abou-Saleh MT, Blazer DG, eds. Principles and Practice of Geriatric Psychiatry . 2nd ed. West Sussex: John Wiley & Sons Ltd; 2002:71-74.
  33. [40]40. Lowsky DJ, Olshansky SJ, Bhattacharya J, Goldman DP. Heterogeneity in healthy aging. J Gerontol A Biol Sci Med Sci . 2014;69(6):640-649.
  34. [41]41. Jylh € av € a J, Pedersen NL, H € agg S. Biological age predictors. EBioMedicine . 2017; 21:29-36.
  35. [42]42. Baker GT III, Sprott RL. Biomarkers of aging. Exp Gerontol . 1988;23(4-5): 223-239.
  36. [43]43. Soto-Perez-de-Celis E, Li D, Yuan Y, Lau YM, Hurria A. Functional versus chronological age: geriatric assessments to guide decision making in older patients with cancer. Lancet Oncol . 2018;19(6):e305-e316.
  37. [45]45. Studenski S, Perera S, Wallace D, et al. Physical performance measures in the clinical setting. J Am Geriatr Soc . 2003;51(3):314-322.
  38. [47]47. Abellan van Kan G, Rolland Y, Andrieu S, et al. Gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people an International Academy on Nutrition and Aging (IANA) Task Force. J Nutr Health Aging . 2009;13(10):881-889.
  39. [50]50. De Vries NM, Staal JB, Van Ravensberg CD, Hobbelen JSM, Rikkert MO, Nijhuis-Van der Sanden M. Outcome instruments to measure frailty: a systematic review. Ageing Res Rev . 2011;10(1):104-114.
  40. [52]52. Hurria A, Cirrincione CT, Muss HB, et al. Implementing a geriatric assessment in cooperative group clinical cancer trials: CALGB 360401. J Clin Oncol . 2011;29(10):1290-1296.
  41. [53]53. Hurria A, Gupta S, Zauderer M, et al. Developing a cancer-specific geriatric assessment: a feasibility study. Cancer . 2005;104(9):1998-2005.
  42. [54]54. Hurria A, Akiba C, Kim J, et al. Reliability, validity, and feasibility of a computer-based geriatric assessment for older adults with cancer. J Oncol Pract . 2016;12(12):e1025-e1034.
  43. [55]55. Extermann M, Boler I, Reich RR, et al. Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-age Patients (CRASH) score. Cancer . 2012;118(13):3377-3386.
  44. [56]56. Avelino-Silva TJ, Farfel JM, Curiati JA, Amaral JR, Campora F, Jacob-Filho W. Comprehensive geriatric assessment predicts mortality and adverse outcomes in hospitalized older adults. BMC Geriatr . 2014;14(1):129. doi: 10.1186/1471-2318-14-129. · DOI
  45. [57]57. Jonna S, Chiang L, Liu J, Carroll MB, Flood K, Wildes TM. Geriatric assessment factors are associated with mortality after hospitalization in older adults with cancer. Support Care Cancer . 2016;24(11):4807-4813.
  46. [58]58. Sargent-Cox KA, Anstey KJ, Luszcz MA. The relationship between change in self-perceptions of aging and physical functioning in older adults. Psychol Aging . 2012;27(3):750-760.
  47. [59]59. Levy BR, Slade MD, Kasl SV. Longitudinal benefit of positive self-perceptions of aging on functional health. J Gerontol B Psychol Sci Soc Sci . 2002;57(5): P409-P417. |
  48. [60]60. Demakakos P, Biddulph JP, de Oliveira C, Tsakos G, Marmot MG. Subjective social status and mortality: the English Longitudinal Study of Ageing. Eur J Epidemiol . 2018;33(8):729-739.
  49. [62]62. Lai J-S, Wagner LI, Jacobsen PB, Cella D. Self-reported cognitive concerns and abilities: two sides of one coin? Psychooncology . 2014;23(10):1133-1141.
  50. [63]63. Wefel JS, Vardy J, Ahles T, Schagen SB. International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol . 2011;12(7):703-708.
  51. [66]66. Simonsick EM, Schrack JA, Glynn NW, Ferrucci L. Assessing fatigability in mobility-intact older adults. J Am Geriatr Soc . 2014;62(2):347-351.
  52. [67]67. Simonsick EM, Glynn NW, Jerome GJ, Shardell M, Schrack JA, Ferrucci L. Fatigued, but not frail: perceived fatigability as a marker of impending decline in mobility-intact older adults. J Am Geriatr Soc . 2016;64(6):1287-1292.
  53. [68]68. Deelen J, Beekman M, Uh H-W, et al. Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited. Aging Cell . 2011;10(4):686-698.
  54. [69]69. Hill S, Van Remmen H. Mitochondrial stress signaling in longevity: a new role for mitochondrial function in aging. Redox Biol . 2014;2:936-944.
  55. [70]70. Mulder H, Ling C. Mitochondrial dysfunction in pancreatic beta-cells in Type 2 diabetes. Mol Cell Endocrinol . 2009;297(1-2):34-40.
  56. [72]72. 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.
  57. [73]73. He S, Sharpless NE. Senescence in health and disease. Cell . 2017;169(6): 1000-1011.
  58. [74]74. 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.
  59. [76]76. Horvath S, Raj K. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet . 2018;19(6):371-384.
  60. [78]78. Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging . 2018;10(4):573-591.
  61. [79]79. Liu Z, Kuo P-L, Horvath S, Crimmins E, Ferrucci L, Levine M. A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: a cohort study. PLoS Med . 2018;15(12):e1002718.
  62. [80]80. Mor V, Laliberte L, Morris JN, Wiemann M. The Karnofsky Performance Status Scale. An examination of its reliability and validity in a research setting. Cancer . 1984;53(9):2002-2007.
  63. [81]81. Manig L, K € asmann L, Janssen S, Schild SE, Rades D. Simplified comorbidity score and Eastern Cooperative Oncology Group performance score predicts survival in patients receiving organ-preserving treatment for bladder cancer. Anticancer Res . 2017;37(5):2693-2696.
  64. [82]82. Rades D, Bolm L, Kaesmann L, Bartscht T. Karnofsky performance score is predictive of survival after palliative irradiation of metastatic bile duct cancer. Anticancer Res . 2017;37(2):949-951.
  65. [83]83. Cesari M, Kritchevsky SB, Newman AB, et al. Added value of physical performance measures in predicting adverse health-related events: results from the Health, Aging And Body Composition Study. J Am Geriatr Soc . 2009;57(2): 251-259.
  66. [84]84. Fries JF, Lingala B, Siemons L, et al. Extending the floor and the ceiling for assessment of physical function. Arthritis Rheumatol . 2014;66(5):1378-1387.
  67. [85]85. Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci . 2007;62(7):722-727.
  68. [86]86. Rockwood K, Mitnitski A. Frailty defined by deficit accumulation and geriatric medicine defined by frailty. Clin Geriatr Med . 2011;27(1):17-26.
  69. [87]87. Rockwood K, Song X, MacKnight C, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ . 2005;173(5):489-495.
  70. [88]88. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet . 2013;381(9868):752-762.
  71. [89]89. Balducci L. Aging, frailty, and chemotherapy. Cancer Control . 2007;14(1):7-12.
  72. [90]90. Crow RS, Lohman MC, Titus AJ, et al. Mortality risk along the frailty spectrum: data from the National Health and Nutrition Examination Survey 1999 to 2004. J Am Geriatr Soc . 2018;66(3):496-502.
  73. [91]91. Owusu C, Berger NA. Comprehensive geriatric assessment in the older cancer patient: coming of age in clinical cancer care. Clin Pract (Lond) . 2014;11(6): 749-762. |
  74. [92]92. Soubeyran P, Fonck M, Blanc-Bisson C, et al. Predictors of early death risk in older patients treated with first-line chemotherapy for cancer. J Clin Oncol . 2012;30(15):1829-1834.
  75. [93]93. Walter LC, Brand RJ, Counsell SR, et al. Development and validation of a prognostic index for 1-year mortality in older adults after hospitalization. JAMA . 2001;285(23):2987-2994.
  76. [94]94. Carey EC, Covinsky KE, Lui LY, Eng C, Sands LP, Walter LC. Prediction of mortality in community-living frail elderly people with long-term care needs. J Am Geriatr Soc . 2008;56(1):68-75.
  77. [95]95. Mohile SG, Dale W, Somerfield MR, et al. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. J Clin Oncol . 2018;36(22):2326-2347.
  78. [96]96. Wildiers H, Heeren P, Puts M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol . 2014;32(24):2595-2603.
  79. [97]97. Mohile SG, Velarde C, Hurria A, et al. Geriatric assessment-guided care processes for older adults: a Delphi consensus of geriatric oncology experts. J Natl Compr Canc Netw . 2015;13(9):1120-1130.
  80. [98]98. Hurria A, Mohile S, Gajra A, et al. Validation of a prediction tool for chemotherapy toxicity in older adults with cancer. J Clin Oncol . 2016;34(20): 2366-2371.
  81. [99]99. Rockwood K, Howlett SE, MacKnight C, et al. Prevalence, attributes, and outcomes of fitness and frailty in community-dwelling older adults: report from the Canadian Study of Health and Aging. J Gerontol A Biol Sci Med Sci . 2004;59(12):1310-1317.
  82. [100]100. Ahles TA, Saykin AJ, McDonald BC, et al. Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve. J Clin Oncol . 2010;28(29):4434-4440.
  83. [101]101. Ahles TA, Root JC, Ryan EL. Cancer-and cancer treatment-associated cognitive change: an update on the state of the science. J Clin Oncol . 2012;30(30): 3675-3686.
  84. [102]102. Mandelblatt JS, Small BJ, Luta G, et al. Cancer-related cognitive outcomes among older breast cancer survivors in the Thinking and Living With Cancer Study. J Clin Oncol . 2018;36(32):3211-3222.
  85. [103]103. Horowitz TS, Suls J, Trevi ~ no M. A call for a neuroscience approach to cancerrelated cognitive impairment. Trends Neurosci . 2018;41(8):493-496.
  86. [104]104. van Westrhenen A, Smidt LCA, Seute T, et al. Diagnostic markers for CNS lymphoma in blood and cerebrospinal fluid: a systematic review. Br J Haematol . 2018;182(3):384-403.
  87. [105]105. Ahles TA, Li Y, McDonald BC, et al. Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: the impact of APOE and smoking. Psychooncology . 2014;23(12):1382-1390.
  88. [107]107. Almada AE, Wagers AJ. Molecular circuitry of stem cell fate in skeletal muscle regeneration, ageing and disease. Nat Rev Mol Cell Biol . 2016;17(5): 267-279.
  89. [108]108. Franco I, Johansson A, Olsson K, et al. Somatic mutagenesis in satellite cells associates with human skeletal muscle aging. Nat Commun . 2018;9(1): 800-811.
  90. [109]109. Scuric Z, Carroll JE, Bower JE, et al. Biomarkers of aging associated with past treatments in breast cancer survivors. NPJ Breast Cancer . 2017;3(1):50.
  91. [110]110. Carroll JE, Van Dyk K, Bower JE, et al. Cognitive performance in survivors of breast cancer and markers of biological aging. Cancer . 2019;125(2):298-306.
  92. [111]111. Aunon JR, Cho WC, Soreide K. The biology of aging and cancer: a brief overview of shared and divergent molecular hallmarks. Aging Dis . 2017;8(5): 628-642.
  93. [112]112. Sousa-Victor P, Mu ~ noz-C anoves P. Regenerative decline of stem cells in sarcopenia. Mol Aspects Med . 2016;50:109-117.
  94. [113]113. Noronha-Matos JB, Coerreia-de-Sa P. Mesenchymal stem cells ageing: targeting the 'purinome' to promote osteogenic differentiation and bone repair. J Cell Physiol . 2016;231(9):1852-1861.
  95. [115]115. Cupit-Link MC, Kirkland JL, Ness KK, et al. Biology of premature ageing in survivors of cancer. ESMOOpen . 2017;2(5):e000250.
  96. [116]116. Liu Y, Sanoff HK, Cho H, et al. Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging. Aging Cell . 2009;8(4):439-448.
  97. [118]118. Shaw AC, Joshi S, Greenwood H, Panda A, Lord JM. Aging of the innate immunesystem. Curr Opin Immunol . 2010;22(4):507-513.
  98. [119]119. Caruso C, Lio D, Cavallone L, Franceschi C. Aging, longevity, inflammation, and cancer. Ann N Y Acad Sci . 2004;1028(1):1-13.
  99. [120]120. Green DR, Galluzzi L, Kroemer G. Mitochondria and the autophagyinflammation-cell death axis in organismal aging. Science . 2011;333(6046): 1109-1112.
  100. [121]121. Krabbe KS, Pedersen M, Bruunsgaard H. Inflammatory mediators in the elderly. Exp Gerontol . 2004;39(5):687-699.
  101. [122]122. Goto M. Inflammaging (inflammation þ aging): a driving force for human aging based on an evolutionarily antagonistic pleiotropy theory? Bioscience Trends . 2008;2(6):218-230.
  102. [123]123. Sebastiani P, Thyagarajan B, Sun F, et al. Biomarker signatures of aging. Aging Cell . 2017;16(2):329-338.
  103. [125]125. Lin L, Park S, Lakatta EG. RAGE signaling in inflammation and arterial aging. Front Biosci (Landmark Ed) . 2009;14:1403-1413.
  104. [126]126. Demaria M, O'Leary MN, Chang J, et al. Cellular senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer Discov . 2017;7(2): 165-176.
  105. [127]127. H € am € al € ainen S, Kuittinen T, Matinlauri I, Nousiainen T, Koivula I, Jantunen E. Neutropenic fever and severe sepsis in adult acute myeloid leukemia (AML) patients receiving intensive chemotherapy: causes and consequences. Leuk Lymphoma . 2008;49(3):495-501.
  106. [128]128. Marioni RE, Shah S, McRae AF, et al. DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol . 2015;16(1):25.
  107. [129]129. 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.
  108. [130]130. Breitling LP, Saum K-U, Perna L, Scho ¨ttker B, Holleczek B, Brenner H. Frailty is associated with the epigenetic clock but not with telomere length in a Germancohort. Clin Epigenet . 2016;8(1):21.
  109. [132]132. Zheng Y, Joyce BT, Colicino E, et al. Blood epigenetic age may predict cancer incidence and mortality. EBioMedicine . 2016;5:68-73.
  110. [133]133. Durso DF, Bacalini MG, Sala C, et al. Acceleration of leukocytes' epigenetic age as an early tumor and sex-specific marker of breast and colorectal cancer. Oncotarget . 2017;8(14):23237-23245.
  111. [134]134. Levine ME, Hosgood HD, Chen B, Absher D, Assimes T, Horvath S. DNA methylation age of blood predicts future onset of lung cancer in the Women'sHealth Initiative. Aging (Albany NY). 2015;7(9):690-700.
  112. [135]135. Ambatipudi S, Horvath S, Perrier F, et al. DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility. Eur J Cancer . 2017;75:299-307.
  113. [136]136. Belsky DW, Caspi A, Houts R, et al. Quantification of biological aging in young adults. Proc Natl Acad Sci USA . 2015;112(30):E4104-E4110.
  114. [138]138. Belsky DW, Moffitt TE, Cohen AA, et al. Eleven telomere, epigenetic clock, and biomarker-composite quantifications of biological aging: do they measure the same thing? AmJEpidemiol . 2018;187(6):1220-1230.
  115. [139]139. Moffitt TE, Belsky DW, Danese A, Poulton R, Caspi A. The Longitudinal Study of Aging in Human Young Adults: knowledge gaps and research agenda. J Gerontol A Biomed Sci Med Sci . 2017;72(2):210-215.
  116. [140]140. Rapaport MH, Maddux RE. Challenges in the development of clinical trials for major depressive disorder: lessons learned from trials in minor depression. Dialogues Clin Neurosci . 2002;4(4):402-407.
  117. [141]141. Levit LA, Singh H, Klepin HD, Hurria A. Expanding the evidence base in geriatric oncology: action items from an FDA-ASCO workshop. J Natl Cancer Inst . 2018;110(11):1163-1170.
  118. [142]142. Hubbard JM, Jatoi A. Incorporating biomarkers of frailty and senescence in cancer therapeutic trials. J Gerontol A Biomed Sci Med Sci . 2015;70(6):722-728.
  119. [143]143. Liao P, Ostrom QT, Stetson L, Barnholtz-Sloan JS. Models of epigenetic age capture patterns of DNA methylation in glioma associated with molecular subtype, survival, and recurrence. Neuro-Oncology . 2018;20(7): 942-953.
  120. [144]144. Marwitz S, Heinbockel L, Scheufele S, et al. Fountain of youth for squamous cell carcinomas? On the epigenetic age of non-small cell lung cancer and corresponding tumor-free lung tissues. Int J Cancer . 2018;143(12):3061-3070.
  121. [145]145. Klemera P, Doubal S. A new approach to the concept and computation of biological age. Mech Ageing Dev . 2006;127(3):240-248.
  122. [146]146. Gruenewald TL, Seeman TE, Ryff CD, Karlamangla AS, Singer BH. Combinations of biomarkers predictive of later life mortality. Proc Natl Acad Sci USA . 2006;103(38):14158-14163.
  123. [147]147. Cohen AA, Milot E, Li Q, et al. Detection of a novel, integrative aging process suggests complex physiological integration. PLoS One . 2015;10(3): e0116489.
  124. [148]148. Levine ME. Modeling the rate of senescence: can estimated biological age predict mortality more accurately than chronological age? J Gerontol A Biomed Sci Med Sci . 2013;68(6):667-674.
  125. [149]149. Wiley JF, Bei B, Bower JE, Stanton AL. Relationship of psychosocial resources with allostatic load: a systematic review. Psychosom Med . 2017; 79(3):283-292.
  126. [151]151. Szanton SL, Allen JK, Seplaki CL, Bandeen-Roche K, Fried LP. Allostatic load and frailty in the Women's Health and Aging studies. Biol Res Nurs . 2008;10(3): 248-256.

Cited by

Sorted by citations

Authors
Guida, J. L., Ahles, T. A., Belsky, D., Campisi, J., Cohen, H. J., DeGregori, J., Fuldner, R., Ferrucci, L., Gallicchio, L., Gavrilov, L., Gavrilova, N., Green, P. A., Jhappan, C., Kohanski, R., Krull, K., Mandelblatt, J., Ness, K. K., O’Mara, A., Price, N., Schrack, J., Studenski, S., Theou, O., Tracy, R. P., & Hurria, A.
Affiliations
National Cancer Institute (US)
Corresponding author
Green, Paige A
ORCID
Venue
JNCI: Journal of the National Cancer Institute
Publisher
Oxford University Press (OUP)
Published
2019-07-18
Volume
111
Issue
12
Pages
1245-1254
ISSN
  • 0027-8874 (ISSN-L)
  • 1460-2105
DOI
10.1093/jnci/djz136
PMC
PMC7962788
OpenAlex
W2963836211
Cited by
216
References
21
Citations by year
2026: 29 · 2025: 27 · 2024: 45 · 2023: 36 · 2022: 33 · 2021: 30 · 2020: 13 · 2019: 2
FWCI
8.14
Type
journal article
Language
en
Open access
Licence
Locations
  • JNCI Journal of the National Cancer Institute (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (R01CA172119, R01CA129769, U54CA137788, P30CA008748, R01CA180175, R21AG054849, R01CA174794, R01CA215405, R35CA197289, R01CA200859, P30AG021334, R21AG053198, U01AG057545, R01AG052964)
  • Jacobs Foundation
  • American Association for Cancer Research
Topics
  • Health Sciences › Medicine › Oncology › Cancer survivorship and care
  • Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Childhood Cancer Survivors' Quality of Life
Keywords
cancer survivors, accelerated aging, aging phenotypes, frailty, sarcopenia, cardiac dysfunction, mild cognitive impairment, late effects of cancer treatment, long-term morbidity, aging trajectories, healthy aging, data integration, longitudinal study
MeSH terms
Cancer Survivors, Frailty, Physical Functional Performance, Age Factors, Aging, Chronic Disease, Heart Diseases, Humans, Neoplasms, Phenotype, United States, Biomarkers, Consensus Development Conferences, NIH as Topic, Evidence-Based Medicine, National Cancer Institute (U.S.), Sarcopenia, Cognitive Dysfunction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review