Frailty biomarkers under the perspective of geroscience: A narrative review

Cellular and molecular aging biomarkers might contribute to identify at-risk individuals for frailty before overt clinical manifestations appear. Although studies on the associations of aging biomarkers and frailty exist, no investigation has gathered this information using a structured framework for identifying aging biomarkers; as a result, the evidence on frailty and aging biomarkers is diffuse and incomplete. Therefore, this narrative review aimed to gather information on the associations of the hallmarks of aging and frailty under the perspective of geroscience. The literature on human studies on this topic is sparse and mainly composed of cross-sectional investigations performed in small study samples. The main putative aging biomarkers associated to frailty were: mitochondrial DNA copy number (genomic instability and mitochondrial dysfunction), telomere length (telomere attrition), global DNA methylation (epigenetic alterations), Hsp70 and Hsp72 (loss of proteostasis), IGF-1 and SIRT1 (deregulated nutrient-sensing), GDF-15 (mitochondrial dysfunction, cellular senescence and altered intercellular communication), CD4 + and CD8 + cell percentages (cellular senescence), circulating osteogenic progenitor (COP) cells (stem cell exhaustion), and IL-6, CRP and TNF-alpha (altered intercellular communication). IGF-1, SIRT1, GDF-15, IL-6, CRP and TNF-alpha presented more evidence among these biomarkers, highlighting the importance of inflammation and nutrient sensing on frailty. Further longitudinal studies investigating biomarkers across the hallmarks of aging would provide valuable information on this topic.