Are aging biomarkers clinically relevant in oncogeriatrics?
Section snippets
Defining aging biomarkers
Aging is associated with a progressive decline in the functional reserve of multiple organ systems [1]. As aging is heterogeneous, this decline has to be assessed individually in the elderly and care adapted not solely on chronological age. Nowadays this assessment is clinical and based upon a geriatric evaluation. In the context of a biological assessment, aging biomarkers could be defined as easily accessible biological markers predictive of the loss of functional reserve, estimated through
Aging is associated in vivo with the accumulation of senescent cells
One of the main characteristics during aging both in vivo and in vitro is the accumulation of DNA damage. In cell culture, this results in an exponential accumulation of senescent cells [10]. Senescence represents a response to DNA damage signaling, inducing a permanent growth arrest. Senescence can be induced by the stepwise accumulation of DNA damage as a consequence of cell divisions and telomere shortening (replicative senescence). Moreover, senescence can also abruptly be induced by
Aging biomarkers in oncogeriatrics
Therapeutic decisions in oncogeriatrics are usually elaborated upon benefit/risk ratio and an evaluation of patients’ general health, estimated through different algorithms [1]. Another challenging question, in the context of adjuvant treatments, is the estimation of the expected survival, again nowadays estimated upon clinical scores [57]. Good aging biomarkers should, on the basis of what was previously developed, (1) give a better estimation of patients’ general health and expected survival,
Biomarkers of DNA damage, telomere dysfunction, and senescence
Considering the above described evidences, following classes of markers could be evaluated as biomarkers for aging and an increased cancer risk: (1) accumulation of DNA damage indicated by upstream markers of DNA damage (γH2AX, 53BP1, MDC1, etc.), (2) markers of telomere dysfunction (telomere shortening, altered expression of proteins of the shelterin, anaphase bridges and chromosomal imbalances), (3) downstream components of DNA damage signaling and senescence induction (p21, p16 and SA-βGAL),
Controversies and limits of the concept of aging biomarkers
However, all the previously described pieces of evidence on biomarkers of aging stay a matter of debate. One must emphasize that, although senescent cells are usually described in vitro, they are hardly detectable in vivo. Two hypotheses for that phenomenon are that the cells generally do not arrive to the senescent state or are recognized and destroyed by the immune system. As a consequence, the harmful impact of senescent cells, through the impairment of tissue renewal, the senescence
Conclusion – perspectives
Since oncogeriatrics treatment decisions depend not only on the tumor characteristics but also on the ability of the patient to tolerate treatments and on the benefit/risk ratio, tools are needed in order to assess risk factors and to predict outcome and therapeutic benefits for elderly cancer patients. Aging biomarkers could become a quantitative, reproducible and quick help for treatment decisions. Nevertheless, prospective data are still sparse and the current challenge is to integrate
Reviewers
Hans Wildiers, MD, PhD, University Hospital Gasthuisberg, Dept. of Medical Oncology, Herestraat 49, B-3000 Leuven, Belgium.
Tamas Fulop, MD, PhD, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Department of medicine, IUGS, Pavillon Argyll, Sherbrooke, Quebec J1J 3H5, Canada.
Claire Falandry, MD, PhD acquired a specialization in oncology then in geriatrics. She was graduated in molecular biology in Pr E. Gilson's “Epigenetic and telomeric regulations” team. She acquired a post-doctoral experience in the Institute of Molecular Medicine and Max Planck Department on Stem Cell Aging headed by Pr K.L. Rudolph. She was the scientific coordinator of several elderly specific multicentric trials.
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Do neutrophil to lymphocyte ratio and platelet to lymphocyte ratio associate with frailty in elderly inpatient with comorbidity?
2022, Experimental GerontologyCitation Excerpt :The mechanism of lymphocytes and muscular function, frailty is indefinite yet. Previous studies have shown that total lymphocyte count in blood in the immune system reduced with aging (Falandry et al., 2013; Brodin and Davis, 2017). Janus kinase-Signal Transducer and Activator of Transcription proteins (JAK-STAT) pathway is a canonical signaling pathway of cell proliferation, Samson LD et al. found that frailer men showing lower pSTAT5 responses in CD4+ and CD8+ T cells and lower IL-10- induced pSTAT3 responses in men were related to higher frailty scores levels (Samson et al., 2022).
Inflammatory markers and overall survival in older adults with cancer
2019, Journal of Geriatric OncologyInclusion of elderly patients in oncology clinical trials
2016, Annals of OncologyBiomarkers to identify and isolate senescent cells
2016, Ageing Research ReviewsCitation Excerpt :Only single-cell markers of senescence will be discussed. Detailed reviews on systemic aging markers have been published previously (Falandry et al., 2013; Pallis et al., 2014). While cellular senescence has been linked to a number of predictable phenotypic traits and representative biomarkers (Table 1), senescent cells are still a heterogeneous population, and this fact significantly complicates a search for a robust senescence biomarker.
Cancer and Aging: General Principles, Biology, and Geriatric Assessment.
2016, Clinics in Geriatric MedicineCitation Excerpt :However, a direct mechanistic link between these inflammatory and coagulation markers and functional decline has not been clearly established. Furthermore, in patients with cancer, when the tumor has not been removed, these markers are often produced by the actual cancer itself, resulting in difficulties for accurate interpretation of correlation with overall functional age.61 Therefore, chronic inflammatory markers or markers of coagulation may have potentially better utility in the setting of early stage cancer when the tumors have been completely removed.
Claire Falandry, MD, PhD acquired a specialization in oncology then in geriatrics. She was graduated in molecular biology in Pr E. Gilson's “Epigenetic and telomeric regulations” team. She acquired a post-doctoral experience in the Institute of Molecular Medicine and Max Planck Department on Stem Cell Aging headed by Pr K.L. Rudolph. She was the scientific coordinator of several elderly specific multicentric trials.