Average life expectancy has increased considerably in last century, thus increasing the number of elderly people in the population and therefore functional limitations and age-related diseases. In this sense, frailty represents a novel geriatric syndrome that is characterized by a loss of functional capacity and a decline in the ability to respond to physiological stress, resulting in increased vulnerability of the individual and negative health outcomes. Relatively little is known regarding the pathophysiology of this syndrome and the molecular mechanisms underlying frailty remain poorly understood. In order to address this issue, we analyzed the transcriptomic profile of a set of robust and frail individuals from the Basque Country and we obtain differentially expressed genes associated with the frailty status. We validated their expression in different cohorts as well as after different types of interventions and we discovered their role in cell aging; overall, revealing senescence related pathways as novel mechanisms underlying the pathobiology of frailty.

In the other hand, centenarians display extreme longevity, which is accompanied by better cognitive function, fewer comorbidities, and greater quality of life, and therefore, they have been proposed as a model of healthy aging. In our study, we performed transcriptomic analysis in hippocampus samples of human individuals of different ages, including centenarian individuals, in order to address the molecular mechanisms underlying brain aging. We identified a differential gene expression pattern in centenarians compared to old and young individuals. Overall, our results show that hippocampus of centenarians display high levels of metallothioneins, which are mainly expressed in astrocytes, becoming a defensive mechanism that could provide neuroprotection in the brain during aging.