Biology of frailty: Modulation of ageing genes and its importance to prevent age-associated loss of function.

Frailty is associated with loss of functional reserve as well as with the prediction of adverse events in the old population. The traditional criteria of frailty are based on five physical determinations described in the Cardiovascular Health Study. We propose that biological and genetic markers of frailty should be used to increase the predictive capacity of the established clinical indeces. In recent times, research for biological markers of frailty has gained impetus. Finding a biological markers with diagnostic and prognostic capacity would be a major milestone to identify frailty risk, and also pre-frailty status. In the first section of the manuscript, we review the available biomarkers that help to monitor and prevent the evolution and the efficacy of interventions to delay the onset of frailty and to prevent its progression to incapacity. We also discuss the contribution of genetics to frailty. There are scientific bases that support that genetics influences frailty, although environmental factors probably will have the highest contribution. We review the known SNPs of the genes associated with frailty and classify them, taking into account the pathway in which they are involved. We also highlight the importance of longevity genes and their possible relation with frailty, citing centenarians who reach a very old age as an example of successful ageing. Finally, the reversibility of frailty is discussed. It can potentially be treated with nutritional or pharmacological interventions. However, physical exercise seems to be the most effective strategy to treat and prevent frailty. The last section of the manuscript is devoted to explaining the recommendations on the appropriate design of an exercise protocol to maximize its beneficial effects in a population of frail individuals.