Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors.

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 phase-shift 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.

[1]  K. Ness,et al.  Frailty and aging in cancer survivors. , 2020, Translational research : the journal of laboratory and clinical medicine.

[2]  Jeffrey H. Chuang,et al.  Molecular Biology and Evolution of Cancer: From Discovery to Action , 2019, Molecular biology and evolution.

[3]  K. Ness,et al.  Premature Aging in Young Cancer Survivors. , 2019, Journal of the National Cancer Institute.

[4]  Jack A. Taylor,et al.  Methylation-based biological age and breast cancer risk. , 2019, Journal of the National Cancer Institute.

[5]  M. Irwin,et al.  Cognitive performance in survivors of breast cancer and markers of biological aging , 2018, Cancer.

[6]  Luigi Ferrucci,et al.  A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study , 2018, PLoS medicine.

[7]  Laura A. Levit,et al.  Expanding the Evidence Base in Geriatric Oncology: Action Items From an FDA-ASCO Workshop , 2018, Journal of the National Cancer Institute.

[8]  K. Rabe,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 , 2018, International journal of cancer.

[9]  J. VanMeter,et al.  Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study. , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  L. Ferrucci,et al.  Contrasting characteristics of daily physical activity in older adults by cancer history , 2018, Cancer.

[11]  T. Horowitz,et al.  A Call for a Neuroscience Approach to Cancer-Related Cognitive Impairment , 2018, Trends in Neurosciences.

[12]  J. Barnholtz-Sloan,et al.  Models of epigenetic age capture patterns of DNA methylation in glioma associated with molecular subtype, survival, and recurrence , 2018, Neuro-oncology.

[13]  S. Kesler,et al.  Neurocognitive Outcomes and Interventions in Long-Term Survivors of Childhood Cancer. , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  Yuan Yuan,et al.  Functional versus chronological age: geriatric assessments to guide decision making in older patients with cancer. , 2018, The Lancet. Oncology.

[15]  S. Nierkens,et al.  Diagnostic markers for CNS lymphoma in blood and cerebrospinal fluid: a systematic review , 2018, British journal of haematology.

[16]  H. Cohen,et al.  Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology. , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  M. Marmot,et al.  Subjective social status and mortality: the English Longitudinal Study of Ageing , 2018, European Journal of Epidemiology.

[18]  J. Root,et al.  Cognitive Effects of Cancer and Cancer Treatments. , 2018, Annual review of clinical psychology.

[19]  Steve Horvath,et al.  DNA methylation-based biomarkers and the epigenetic clock theory of ageing , 2018, Nature Reviews Genetics.

[20]  S. Studenski,et al.  Fatigability and endurance performance in cancer survivors: Analyses from the Baltimore Longitudinal Study of Aging , 2018, Cancer.

[21]  C. Franceschi,et al.  The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates , 2018, Front. Med..

[22]  M. Levine,et al.  An epigenetic biomarker of aging for lifespan and healthspan , 2018, bioRxiv.

[23]  S. Bartels,et al.  Mortality Risk Along the Frailty Spectrum: Data from the National Health and Nutrition Examination Survey 1999 to 2004 , 2018, Journal of the American Geriatrics Society.

[24]  Carmen L. Wilson,et al.  Clinical impact of sedentary behaviors in adult survivors of acute lymphoblastic leukemia: A report from the St. Jude Lifetime Cohort study , 2018, Cancer.

[25]  A. Pagnani,et al.  Somatic mutagenesis in satellite cells associates with human skeletal muscle aging , 2018, Nature Communications.

[26]  R. Levine,et al.  Clonal Hematopoiesis and Evolution to Hematopoietic Malignancies. , 2018, Cell stem cell.

[27]  T. Ahles,et al.  New Challenges in Psycho‐Oncology Research IV: Cognition and cancer: Conceptual and methodological issues and future directions , 2018, Psycho-oncology.

[28]  Richie Poulton,et al.  Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing? , 2017, American journal of epidemiology.

[29]  M. Irwin,et al.  Biomarkers of aging associated with past treatments in breast cancer survivors , 2017, npj Breast Cancer.

[30]  N. LeBrasseur,et al.  Biology of premature ageing in survivors of cancer , 2017, ESMO Open.

[31]  D. Cutter,et al.  Risk stratification of childhood cancer survivors necessary for evidence-based clinical long-term follow-up , 2017, British Journal of Cancer.

[32]  Kjetil Søreide,et al.  The Biology of Aging and Cancer: A Brief Overview of Shared and Divergent Molecular Hallmarks , 2017, Aging and disease.

[33]  Shenghui He,et al.  Senescence in Health and Disease , 2017, Cell.

[34]  D. Rades,et al.  Simplified Comorbidity Score and Eastern Cooperative Oncology Group Performance Score Predicts Survival in Patients Receiving Organ-preserving Treatment for Bladder Cancer. , 2017, Anticancer research.

[35]  D. Belsky,et al.  Impact of early personal‐history characteristics on the Pace of Aging: implications for clinical trials of therapies to slow aging and extend healthspan , 2017, Aging cell.

[36]  S. Horvath,et al.  DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility. , 2017, European journal of cancer.

[37]  J. Bower,et al.  Relationship of Psychosocial Resources With Allostatic Load: A Systematic Review , 2017, Psychosomatic medicine.

[38]  Nancy L. Pedersen,et al.  Biological Age Predictors , 2017, EBioMedicine.

[39]  A. Farioli,et al.  Clinical Target Volume in Biliary Carcinoma: A Systematic Review of Pathological Studies. , 2017, Anticancer research.

[40]  Christine Nardini,et al.  Acceleration of leukocytes’ epigenetic age as an early tumor and sex-specific marker of breast and colorectal cancer , 2017, Oncotarget.

[41]  S. Studenski,et al.  Muscle strength mediates the relationship between mitochondrial energetics and walking performance , 2017, Aging cell.

[42]  D. Belsky,et al.  The Longitudinal Study of Aging in Human Young Adults: Knowledge Gaps and Research Agenda , 2017, The journals of gerontology. Series A, Biological sciences and medical sciences.

[43]  D. Rades,et al.  Karnofsky Performance Score Is Predictive of Survival After Palliative Irradiation of Metastatic Bile Duct Cancer. , 2017, Anticancer research.

[44]  B. Kennedy,et al.  Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse. , 2017, Cancer discovery.

[45]  R. Andridge,et al.  Inflammatory Cytokines and Comorbidity Development in Breast Cancer Survivors Versus Noncancer Controls: Evidence for Accelerated Aging? , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[46]  Paola Sebastiani,et al.  Biomarker signatures of aging , 2017, Aging cell.

[47]  H. Cohen,et al.  Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With Cancer. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[48]  H. Cohen,et al.  Reliability, Validity, and Feasibility of a Computer-Based Geriatric Assessment for Older Adults With Cancer. , 2016, Journal of oncology practice.

[49]  P. Correia‐de‐Sá,et al.  Mesenchymal Stem Cells Ageing: Targeting the “Purinome” to Promote Osteogenic Differentiation and Bone Repair , 2016, Journal of cellular physiology.

[50]  P. Muñoz-Cánoves,et al.  Regenerative decline of stem cells in sarcopenia. , 2016, Molecular aspects of medicine.

[51]  S. Jonna,et al.  Geriatric assessment factors are associated with mortality after hospitalization in older adults with cancer , 2016, Supportive Care in Cancer.

[52]  K. Ness,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 , 2016, The Lancet. Oncology.

[53]  K. Wieczorowska-Tobis,et al.  Interleukin-6 and C-reactive protein, successful aging, and mortality: the PolSenior study , 2016, Immunity & Ageing.

[54]  A. Brunet,et al.  The Aging Epigenome. , 2016, Molecular cell.

[55]  L. Ferrucci,et al.  Fatigued, but Not Frail: Perceived Fatigability as a Marker of Impending Decline in Mobility‐Intact Older Adults , 2016, Journal of the American Geriatrics Society.

[56]  Albert E. Almada,et al.  Molecular circuitry of stem cell fate in skeletal muscle regeneration, ageing and disease , 2016, Nature Reviews Molecular Cell Biology.

[57]  S. Studenski,et al.  31P Magnetic Resonance Spectroscopy Assessment of Muscle Bioenergetics as a Predictor of Gait Speed in the Baltimore Longitudinal Study of Aging. , 2016, The journals of gerontology. Series A, Biological sciences and medical sciences.

[58]  Marten Scheffer,et al.  Slowing Down of Recovery as Generic Risk Marker for Acute Severity Transitions in Chronic Diseases , 2016, Critical care medicine.

[59]  Bernd Holleczek,et al.  Frailty is associated with the epigenetic clock but not with telomere length in a German cohort , 2016, Clinical Epigenetics.

[60]  E. Colicino,et al.  Blood Epigenetic Age may Predict Cancer Incidence and Mortality , 2016, EBioMedicine.

[61]  A. Pezeshki,et al.  Naturally occurring p16Ink4a-positive cells shorten healthy lifespan , 2016, Nature.

[62]  L. Jones,et al.  Cancer Treatment as an Accelerated Aging Process: Assessment, Biomarkers, and Interventions. , 2016, American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting.

[63]  S. Mohile,et al.  Geriatric Assessment-Guided Care Processes for Older Adults: A Delphi Consensus of Geriatric Oncology Experts. , 2015, Journal of the National Comprehensive Cancer Network : JNCCN.

[64]  M. Levine,et al.  DNA methylation age of blood predicts future onset of lung cancer in the women's health initiative , 2015, Aging.

[65]  Christophe Trefois,et al.  Critical transitions in chronic disease: transferring concepts from ecology to systems medicine. , 2015, Current opinion in biotechnology.

[66]  D. Belsky,et al.  Quantification of biological aging in young adults , 2015, Proceedings of the National Academy of Sciences.

[67]  A. Jatoi,et al.  Incorporating biomarkers of frailty and senescence in cancer therapeutic trials. , 2015, The journals of gerontology. Series A, Biological sciences and medical sciences.

[68]  William H. Bisson,et al.  Causes of genome instability: the effect of low dose chemical exposures in modern society. , 2015, Carcinogenesis.

[69]  Carmen L. Wilson,et al.  Frailty in childhood cancer survivors , 2015, Cancer.

[70]  L. Ferrucci,et al.  Accelerating aging research: How can we measure the rate of biologic aging? , 2015, Experimental Gerontology.

[71]  Christoffer Johansen,et al.  Are we ready to predict late effects? A systematic review of clinically useful prediction models. , 2015, European journal of cancer.

[72]  L. Ferrucci,et al.  Detection of a Novel, Integrative Aging Process Suggests Complex Physiological Integration , 2015, PloS one.

[73]  D. McMillan,et al.  Routine clinical markers of the magnitude of the systemic inflammatory response after elective operation: a systematic review. , 2015, Surgery.

[74]  S. Horvath,et al.  DNA methylation age of blood predicts all-cause mortality in later life , 2015, Genome Biology.

[75]  Steve Horvath,et al.  The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936 , 2015, International journal of epidemiology.

[76]  N. Berger,et al.  Comprehensive geriatric assessment in the older cancer patient: coming of age in clinical cancer care. , 2014, Clinical practice.

[77]  J. Farfel,et al.  Comprehensive geriatric assessment predicts mortality and adverse outcomes in hospitalized older adults , 2014, BMC Geriatrics.

[78]  Jason H. Moore,et al.  Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: the impact of APOE and smoking , 2014, Psycho-oncology.

[79]  D. Cella,et al.  Self‐reported cognitive concerns and abilities: two sides of one coin? , 2014, Psycho-oncology.

[80]  Stephen L. Brown,et al.  Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials , 2014, Radiation oncology journal.

[81]  H. Wildiers,et al.  International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[82]  H. Van Remmen,et al.  Mitochondrial stress signaling in longevity: A new role for mitochondrial function in aging , 2014, Redox Biology.

[83]  A. Jemal,et al.  Cancer treatment and survivorship statistics, 2014 , 2014, CA: a cancer journal for clinicians.

[84]  S Jay Olshansky,et al.  Heterogeneity in healthy aging. , 2014, The journals of gerontology. Series A, Biological sciences and medical sciences.

[85]  Carmen L. Wilson,et al.  Decline in Physical Activity Level in the Childhood Cancer Survivor Study Cohort , 2014, Cancer Epidemiology, Biomarkers & Prevention.

[86]  J. Fries,et al.  Extending the Floor and the Ceiling for Assessment of Physical Function , 2014, Arthritis & Rheumatology.

[87]  J. Ibrahim,et al.  Effect of cytotoxic chemotherapy on markers of molecular age in patients with breast cancer. , 2014, Journal of the National Cancer Institute.

[88]  L. Ferrucci,et al.  Assessing Fatigability in Mobility‐Intact Older Adults , 2014, Journal of the American Geriatrics Society.

[89]  H. Cohen,et al.  Accelerated aging among cancer survivors: from pediatrics to geriatrics. , 2014, American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting.

[90]  Carmen L. Wilson,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. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[91]  S. Horvath DNA methylation age of human tissues and cell types , 2013, Genome Biology.

[92]  Manuel Serrano,et al.  The Hallmarks of Aging , 2013, Cell.

[93]  M. Levine Modeling the rate of senescence: can estimated biological age predict mortality more accurately than chronological age? , 2013, The journals of gerontology. Series A, Biological sciences and medical sciences.

[94]  S. Iliffe,et al.  Frailty in elderly people , 2013, The Lancet.

[95]  L. Partridge,et al.  Genetics of longevity in model organisms: debates and paradigm shifts. , 2013, Annual review of physiology.

[96]  J. Campisi Aging, cellular senescence, and cancer. , 2013, Annual review of physiology.

[97]  T. Ideker,et al.  Genome-wide methylation profiles reveal quantitative views of human aging rates. , 2013, Molecular cell.

[98]  M. Szyper-Kravitz,et al.  The effect of chemotherapy on telomere dynamics: clinical results and possible mechanisms , 2013, Leukemia & lymphoma.

[99]  J. Root,et al.  Cancer- and cancer treatment-associated cognitive change: an update on the state of the science. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[100]  G. Lyman,et al.  Predicting the risk of chemotherapy toxicity in older patients: The Chemotherapy Risk Assessment Scale for High‐Age Patients (CRASH) score , 2012, Cancer.

[101]  A. Ravaud,et al.  Predictors of early death risk in older patients treated with first-line chemotherapy for cancer. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[102]  K. Anstey,et al.  The relationship between change in self-perceptions of aging and physical functioning in older adults. , 2012, Psychology and aging.

[103]  L. Silengo,et al.  The aging effect of chemotherapy on cultured human mesenchymal stem cells. , 2011, Experimental hematology.

[104]  Angela B Mariotto,et al.  Cancer Survivors: A Booming Population , 2011, Cancer Epidemiology, Biomarkers & Prevention.

[105]  D. Green,et al.  Mitochondria and the Autophagy–Inflammation–Cell Death Axis in Organismal Aging , 2011, Science.

[106]  A. Uitterlinden,et al.  Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited , 2011, Aging cell.

[107]  T. Ahles,et al.  International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. , 2011, The Lancet. Oncology.

[108]  H. Cohen,et al.  Implementing a geriatric assessment in cooperative group clinical cancer trials: CALGB 360401. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[109]  Kenneth Rockwood,et al.  Frailty defined by deficit accumulation and geriatric medicine defined by frailty. , 2011, Clinics in geriatric medicine.

[110]  M.W.G. Nijhuis-van der Sanden,et al.  Outcome instruments to measure frailty: A systematic review , 2011, Ageing Research Reviews.

[111]  S. Studenski,et al.  Gait speed and survival in older adults. , 2011, JAMA.

[112]  Andrew J Saykin,et al.  Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[113]  D. Kuh,et al.  Objectively measured physical capability levels and mortality: systematic review and meta-analysis , 2010, BMJ : British Medical Journal.

[114]  Samit R. Joshi,et al.  Aging of the innate immune system. , 2010, Current opinion in immunology.

[115]  J. Bartek,et al.  Cytokine expression and signaling in drug-induced cellular senescence , 2010, Oncogene.

[116]  A. Ng,et al.  Secondary malignancies across the age spectrum. , 2010, Seminars in radiation oncology.

[117]  M. Inzitari,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 , 2009, The journal of nutrition, health & aging.

[118]  S. Carpenter,et al.  Early-warning signals for critical transitions , 2009, Nature.

[119]  Jacqui Smith,et al.  Self-perceptions of aging predict mortality and change with approaching death: 16-year longitudinal results from the Berlin Aging Study. , 2009, Psychology and aging.

[120]  N. Sharpless,et al.  Expression of p16INK4a in peripheral blood T‐cells is a biomarker of human aging , 2009, Aging cell.

[121]  S. Rubin,et al.  Added Value of Physical Performance Measures in Predicting Adverse Health‐Related Events: Results from the Health, Aging and Body Composition Study , 2009, Journal of the American Geriatrics Society.

[122]  L. Fried,et al.  Allostatic Load and Frailty in the Women's Health and Aging Studies , 2009, Biological research for nursing.

[123]  C. Ling,et al.  Mitochondrial dysfunction in pancreatic β-cells in Type 2 Diabetes , 2008, Molecular and Cellular Endocrinology.

[124]  E. Lakatta,et al.  RAGE signaling in inflammation and arterial aging. , 2009, Frontiers in bioscience.

[125]  M. Goto Inflammaging (inflammation + aging): A driving force for human aging based on an evolutionarily antagonistic pleiotropy theory? , 2008, Bioscience trends.

[126]  Judith Campisi,et al.  Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor , 2008, PLoS biology.

[127]  E. Jantunen,et al.  Neutropenic fever and severe sepsis in adult acute myeloid leukemia (AML) patients receiving intensive chemotherapy: Causes and consequences , 2008, Leukemia & lymphoma.

[128]  Catherine Eng,et al.  Prediction of Mortality in Community‐Living Frail Elderly People with Long‐Term Care Needs , 2008, Journal of the American Geriatrics Society.

[129]  J. Campisi,et al.  Cellular senescence: when bad things happen to good cells , 2007, Nature Reviews Molecular Cell Biology.

[130]  A. Mitnitski,et al.  Frailty in relation to the accumulation of deficits. , 2007, The journals of gerontology. Series A, Biological sciences and medical sciences.

[131]  S. Oh,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 , 2007, Acta Haematologica.

[132]  C. Schmitt Cellular senescence and cancer treatment. , 2007, Biochimica et biophysica acta.

[133]  Lodovico Balducci,et al.  Aging, frailty, and chemotherapy. , 2007, Cancer control : journal of the Moffitt Cancer Center.

[134]  Burton H Singer,et al.  Combinations of biomarkers predictive of later life mortality , 2006, Proceedings of the National Academy of Sciences.

[135]  Petr Klemera,et al.  A new approach to the concept and computation of biological age , 2006, Mechanisms of Ageing and Development.

[136]  N. Keating,et al.  Physical and Mental Health Status of Older Long‐Term Cancer Survivors , 2005, Journal of the American Geriatrics Society.

[137]  H. Cohen,et al.  Developing a cancer‐specific geriatric assessment , 2005, Cancer.

[138]  J F Fries,et al.  The promise of PROMIS: using item response theory to improve assessment of patient-reported outcomes. , 2005, Clinical and experimental rheumatology.

[139]  I. McDowell,et al.  A global clinical measure of fitness and frailty in elderly people , 2005, Canadian Medical Association Journal.

[140]  K. Ness,et al.  Performance limitations and participation restrictions among childhood cancer survivors treated with hematopoietic stem cell transplantation: the bone marrow transplant survivor study. , 2005, Archives of pediatrics & adolescent medicine.

[141]  D. Broccoli,et al.  Telomere dynamics in response to chemotherapy. , 2005, Current molecular medicine.

[142]  C. Franceschi,et al.  Aging, Longevity, Inflammation, and Cancer , 2004, Annals of the New York Academy of Sciences.

[143]  Kenneth Rockwood,et al.  Prevalence, attributes, and outcomes of fitness and frailty in community-dwelling older adults: report from the Canadian study of health and aging. , 2004, The journals of gerontology. Series A, Biological sciences and medical sciences.

[144]  H. Bruunsgaard,et al.  Inflammatory mediators in the elderly , 2004, Experimental Gerontology.

[145]  S. Studenski,et al.  Physical Performance Measures in the Clinical Setting , 2003, Journal of the American Geriatrics Society.

[146]  R. Yancik,et al.  Cancer survivors in the United States: age, health, and disability. , 2003, The journals of gerontology. Series A, Biological sciences and medical sciences.

[147]  M. Rapaport,et al.  Challenges in the development of clinical trials for major depressive disorder: lessons learned from trials in minor depression , 2002, Dialogues in clinical neuroscience.

[148]  B. Levy,et al.  Longitudinal benefit of positive self-perceptions of aging on functional health. , 2002, The journals of gerontology. Series B, Psychological sciences and social sciences.

[149]  Soyoung Lee,et al.  A Senescence Program Controlled by p53 and p16INK4a Contributes to the Outcome of Cancer Therapy , 2002, Cell.

[150]  I. Roninson,et al.  Molecular determinants of terminal growth arrest induced in tumor cells by a chemotherapeutic agent , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[151]  Kenneth Rockwood,et al.  Accumulation of Deficits as a Proxy Measure of Aging , 2001, TheScientificWorldJournal.

[152]  J W Rowe,et al.  Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[153]  L. Fried,et al.  Frailty in older adults: evidence for a phenotype. , 2001, The journals of gerontology. Series A, Biological sciences and medical sciences.

[154]  R. Fortinsky,et al.  Development and validation of a prognostic index for 1-year mortality in older adults after hospitalization. , 2000, JAMA.

[155]  D. Hanahan,et al.  The Hallmarks of Cancer , 2000, Cell.

[156]  D. Tulsky,et al.  The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[157]  Diane Podsiadlo,et al.  The Timed “Up & Go”: A Test of Basic Functional Mobility for Frail Elderly Persons , 1991, Journal of the American Geriatrics Society.

[158]  George T. Baker,et al.  Biomarkers of aging , 1988, Experimental Gerontology.

[159]  L. Laliberte,et al.  The Karnofsky performance status scale: An examination of its reliability and validity in a research setting , 1984, Cancer.