Frailty has emerged as a reliable measure of the aging process. Because the early detection of frailty is crucial to prevent or even revert it, the use of biomarkers would allow an earlier and more objective identification of frail individuals. To improve the understanding of the biological features associated with frailty as well as to explore different biomarkers for its early identification, several genetic outcomes-mutagenicity, different types of genetic damage, and cellular repair capacity-were analyzed in a population of older adults classified into frail, prefrail, and nonfrail. Besides, influence of clinical parameters-nutritional status and cognitive status-was evaluated. No association of mutation rate or primary DNA damage with frailty was observed. However, DNA repair capacity showed a nonsignificant tendency to decrease with frailty, and persistent levels of phosphorylated H2AX, as indicative of DNA breakage, increased progressively with frailty severity. These results support the possible use of H2AX phosphorylation to provide information regarding frailty severity. Further investigation is necessary to determine the consistency of the current findings in different populations and larger sample sizes, to eventually standardize biomarkers to be used in clinics, and to fully understand the influence of cognitive impairment.