Frailty in the elderlyanalysis of the relationship with genomic alterations and cell repair

Abstract

Frailty is a multidimensional syndrome characterised by an increased vulnerability. Nowadays, frailty identification is based on phenotypical features. Use of biomarkers for frailty identification would provide a more accurate detection of frail subjects in early stages, when frailty can still be potentially reverted. The main objective of this study was to evaluate the possible association between frailty and several cellular and molecular biomarkers – genomic instability, DNA damage, and DNA repair capacity – so that they can be proposed as frailty biomarkers. To that aim, a cross-sectional study was conducted in a population of older adults (aged 65 or over) classified according to their frailty status. A systematic review of the literature on genetic outcomes related to frailty was conducted to establish the current knowledge on the topic. Besides, the most critical issues limiting the use of the phosphorylated H2AX assay as DNA damage biomarker in human population studies were addressed. Results from the population study showed a significant and progressive increase of micronuclei in lymphocytes and phosphorylated H2AX with frailty severity, supporting their use for frailty identification. No association of frailty with micronuclei in buccal cells, frequency of mutation in T-cell receptor, comet assay, or DNA repair capacity was found.