Evaluating the physiological reserves of older patients with cancer: the value of potential biomarkers of aging?
Aging of an individual entails a progressive decline of functional reserves and loss of homeostasis that eventually lead to mortality. This process is highly individualized and is influenced by multiple genetic, epigenetic and environmental factors. This individualization and the diversity of factors influencing aging result in a significant heterogeneity among people with the same chronological age, representing a major challenge in daily oncology practice. Thus, many factors other than mere chronological age will contribute to treatment tolerance and outcome in the older patients with cancer. Clinical/comprehensive geriatric assessment can provide information on the general health status of individuals, but is far from perfect as a prognostic/predictive tool for individual patients. On the other hand, aging can also be assessed in terms of biological changes in certain tissues like the blood compartment which result from adaptive alterations due to past history of exposures, as well as intrinsic aging processes. There are major signs of 'aging' in lymphocytes (e.g. lymphocyte subset distribution, telomere length, p16INK4A expression), and also in (inflammatory) cytokine expression and gene expression patterns. These result from a combination of the above two processes, overlaying genetic predispositions which contribute significantly to the aging phenotype. These potential "aging biomarkers" might provide additional prognostic/predictive information supplementing clinical evaluation. The purpose of the current paper is to describe the most relevant potential "aging biomarkers" (markers that indicate the biological functional age of patients) which focus on the biological background, the (limited) available clinical data, and technical challenges. Despite their great potential interest, there is a need for much more (validated) clinical data before these biomarkers could be used in a routine clinical setting. This manuscript tries to provide a guideline on how these markers can be integrated in future research aimed at providing such data.
European Organization for Research and Treatment of Cancer Elderly Task Force, Brussels, Belgium. Electronic address: athanasios.pallis@eortc.be.
Athanasios G
AG
Pallis
Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Sigrid
S
Hatse
Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Barbara
B
Brouwers
Center for Medical Research, ZMF, University of Tübingen Medical School, Waldhörnlestr. 22, D-72072 Tübingen, Germany.
Graham
G
Pawelec
Geriatrics Unit, Lyon Sud University Hospital, Pierre-Benite, France; Laboratoire de Biologie Moléculaire de la Cellule, Lyon Sud Medicine Faculty, Lyon University, Lyon, France.
Claire
C
Falandry
Jena University Hospital, Department of Internal Medicine, Erlanger Allee 101, 07747 Jena, Germany.
Ulrich
U
Wedding
Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Belgium.
Lissandra Dal
LD
Lago
Dipartimento Oncologia, Ospedale di Sanremo, Via G Borea, 56, 18038 Sanremo, Italy.
Lazzaro
L
Repetto
Brighton and Sussex Medical School, UK.
Alistair
A
Ring
European Organization for Research and Treatment of Cancer Elderly Task Force, Brussels, Belgium; Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Hans
H
Wildiers
D000368:Aged; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics*; D019317:Evidence-Based Medicine; D005786:Gene Expression Regulation; D019942:Genes, p16; D005819:Genetic Markers / Q000235:genetics*; D015577:Geriatric Assessment; D017408:Guidelines as Topic; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D016131:Lymphocyte Subsets / Q000378:metabolism; D009369:Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D015842:Serine Proteinase Inhibitors / Q000235:genetics; D016615:Telomere / Q000235:genetics
D014408:Biomarkers, Tumor; D005819:Genetic Markers; D018969:Insulin-Like Growth Factor Binding Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors
Aging; Aging genes; CRAMP; Cancer; Chitinase; Elderly; IGF-1; IL-6; Immunosenescence; Inflammaging; MCP-1; RANTES; SASP; Telomeres