Proteostasis and longevity: when does aging really begin?

Aging is a complex process regulated by multiple cellular pathways, including the proteostasis network.The proteostasis network consists of molecular chaperones, stress-response transcription factors, and protein degradation machines that sense and respond to proteotoxic stress and protein misfolding to ensure cell viability.A loss of proteostasis is associated with aging and age-related disorders in diverse model systems, moreover, genetic or pharmacological enhancement of the proteostasis network has been shown to extend lifespan and suppress age-related disease.However, our understanding of the relationship between aging, proteostasis, and the proteostasis network remains unclear.Here, we propose, from studies in Caenorhabditis elegans, that proteostasis collapse is not gradual but rather a sudden and early life event that triggers proteome mismanagement, thereby affecting a multitude of downstream processes.Furthermore, we propose that this phenomenon is not stochastic but is instead a programmed re-modeling of the proteostasis network that may be conserved in other species.As such, we postulate that changes in the proteostasis network may be one of the earliest events dictating healthy aging in metazoans. Aging, proteome integrity, and the proteostasis networkAging is inextricably linked to the world around us and regularly pervades everyday life.Despite this, why organisms age remains a complex mystery that if understood could have profound implications for the quality of human health.While the physiological decline associated with old age is easily recognizable, the mechanisms that determine aging are poorly understood; however, widescale loss of protein homeostasis (proteostasis) is proposed to be one of the "primary hallmarks of aging" [1].