Genomic instability as a main driving factor of unsuccessful ageing: Potential for translating the use of micronuclei into clinical practice

Abstract

Genome instability denotes an increased tendency to alterations in the genome during cell life cycle, driven by a large variety of endogenous and exogenous insults. Ageing is characterized by the presence of damage to various cellular constituents, but genome alterations, randomly accumulating with age in different tissues, constitute the key target in this process, and are believed to be the main factor of ageing. Age-related failure of DNA repair pathways allows DNA lesions to occur more frequently, and their accumulation over time contributes to the age-associated decrease in genome integrity in somatic cells. The micronucleus (MN) test is one of the most widely used assays to evaluate genomic instability in different surrogate tissues. A large number of studies has consistently shown a progressive increase in MN frequency with age, starting from very young age groups onwards. Therefore, MN frequency is a suitable biomarker of genomic instability in ageing. Frailty is a multidimensional geriatric syndrome of unsuccessful ageing, characterized by decreased biological reserves and increased vulnerability to external stressors, involving a higher risk of negative health outcomes. Although there is a well-founded belief that genome instability is involved in the frailty syndrome, only two studies investigated the relationship between MN frequency and frailty, not allowing to draw a definite conclusion on the utility of this biomarker for frailty detection. The use of MN and other genomic biomarkers in the detection and follow-up of patients affected by or at risk of frailty has the potential to accumulate evidence on the clinical impact of this approach in the identification and control of frailty in older people.