Abstract
Biomarkers are essential tools for accurate diagnosis and effective prevention, but their validation is a pending challenge that limits their usefulness, even more so with constructs as complex as frailty. Sarcopenia shares multiple mechanisms with frailty which makes it a strong candidate to provide robust frailty biomarkers. Based on this premise, we studied the temporal evolution of cellular interactome in frailty, from independent patients to dependent ones. Overweight is a recognized cause of frailty in aging, so we studied the altered mechanisms in overweight independent elderly and evaluated their aggravation in dependent elderly. This evidence of the evolution of previously altered mechanisms would significantly support their role as real biomarkers of frailty. The results showed a preponderant role of autophagy in interactome control at both different functional points, modulating other essential mechanisms in the cell, such as mitochondrial capacity or oxidative stress. Thus, the overweight provoked in the muscle of the elderly an overload of autophagy that kept cell survival in apparently healthy individuals. This excessive and permanent autophagic effort did not seem to be able to be maintained over time. Indeed, in dependent elderly, the muscle showed a total autophagic inactivity, with devastating effects on the survival of the cell, which showed clear signs of apoptosis, and reduced functional capacity. The frail elderly are in a situation of weakness that is a precursor of dependence that can still be prevented if detection is early. Hence biomarkers are essential in this context.
Highlights
Aging is usually associated with dependence and disease, approximately 50% of the elderly report in different health surveys that they are in good or very good health (SHARE, 2021), which is usually associated with the absence of important symptoms of possible existing chronic diseases and the absence of disabling diseases (Mearin et al, 2009)
Sarcopenia, the loss of muscle capacity and quality associated with aging, is one of the processes that shares the most characteristics with frailty, so that its study and the knowledge of the factors involved in its development could provide, in parallel, information on the progression from frailty to dependence in the elderly
Like frailty, is a multifactorial process in which multiple alterations, most of them at the muscle fiber level, progressively induce cell failure and reduce the muscle strength and power that characterizes sarcopenia. The fact that these alterations occur simultaneously implies an interrelation that must be taken into account in the assessment of the situation, which forces us to study the cellular interactome in these circumstances
Summary
Aging is usually associated with dependence and disease, approximately 50% of the elderly report in different health surveys that they are in good or very good health (SHARE, 2021), which is usually associated with the absence of important symptoms of possible existing chronic diseases and the absence of disabling diseases (Mearin et al, 2009). For instance, the well-known deleterious effects that obesity causes at the organic level, the drastic decrease in the life expectancy of obese people and their low representativeness in aging, allow us to assume that overweight, but not obesity because it is directly disabling, could be a good model to induce frailty in the elderly. For all these reasons, the detection of frailty in the elderly that, in a predictive manner, induces the delay or disappearance of dependence in aging is one of the main objectives of geriatrics today. The present review is focused in the study of the data published so far showing sarcopenic evolution from independent to highly dependent elderly people, providing with powerful contrasted biomarker predictors
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