Aberrations in Proteostasis Orchestrate The Genotypic and Phenotypic Changes in Aging

Aging is a complex process encompassing both genetic and epigenetic modifications leading to the deterioration of internal systems and health complications. Thus far, pathways highly implicated in aging process seem to converge at some point down the cascades of proteostasis(definition). One of the consequences of an imbalance in proteostasis is the loss of critical cellular protective mechanisms leading to protein misfolding and formation of toxic protein aggregates as one of the key players involved in age-related disorders. Despite its importance, protein aggregation has not received the well merited attention from the research community and as yet, the fundamental mechanisms of aggregation and its complications in aging are not well understood. This paper reviews the present literature on the causes and involvement of protein aggregation in aging and analyzes potential interconnections between different pathways implicated in aging process with a focus on mammalian target of mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">rapamycin(definition). Further, it presents the imbalance in proteostasis as the driving force in aging and proposes the increasing levels of reactive oxygen species as the main culprit in induction of protein aggregation leading to DNA damage and aging phenotype in normal cells. According to the numerous findings in relation to the involvement of protein aggregation in the dysfunction of cellular components, it is