Selective autophagy in the maintenance of cellular homeostasis in aging organisms

Abstract

Altered cellular homeostasis, accumulation of damaged non-functional organelles and presence of protein inclusions are characteristics shared by almost all types of differentiated cells in aged organisms. Cells rely on quality control mechanisms to prevent the occurrence of these events and the subsequent cellular compromise associated with them. What goes wrong in aging cells? Growing evidence supports gradual malfunctioning with age of the cellular quality control systems. In this review, we focus on autophagy, a catabolic process that contributes to the maintenance of cellular homeostasis through the degradation of unwanted and damaged components in lysosomes. We describe recent advances on the molecular characterization of this process, its different variants and the multiplicity of functions attributed to them. Autophagic dysfunction has been identified in severe human disorders, many of which worsen with age. We comment on the contribution of an adequate autophagic function to longevity, and the negative impact on health-span of the age-dependent decline in autophagic function.

Molecular alterations in proteasomes of rat liver during aging result in altered proteolytic activities

“…This observation parallels the biphasic run of the rate of overall protein degradation in aging rat (Ward 1988). Mechanistically, autophagy is divided into three different types -macroautophagy, microautophagy and chaperone-mediated autophagy (Cuervo 2004) -and at least two of them, macroautophagy and chaperonemediated autophagy, are known to be compromised in liver tissue during aging (for review, see Rajawat et al 2009;Hubbard et al 2012).…”

Oxidised protein metabolism: recent insights

“…For a detailed review of these pathways and their molecular components please see (Höhn et al, 2013;Navarro-Yepes et al, 2014). Of these cellular digestive mechanisms, macroautophagy is the best characterised and is utilised to selectively degrade organelles such as mitochondria (mitophagy), peroxisomes (pexophagy) and ribosomes (ribophagy) (Hubbard et al, 2012). Decreases in lysosomal proteolysis that occur naturally during ageing have been associated with the accumulation of oxidised proteins and lipofuscin (Lynch and Bi, 2003).…”

GCN5-like Protein 1 (GCN5L1) Controls Mitochondrial Content through Coordinated Regulation of Mitochondrial Biogenesis and Mitophagy

“…Perhaps best known for its recycling of cellular components during periods of nutrient deprivation, autophagy is also necessary for the orderly removal of proteins, aggregates and organelles that have reached the end of their useful life (1)(2)(3). In the case of mitochondria, removal by autophagy (also known as "mitophagy") is a key housekeeping process, which is used to safely remove damaged or redundant organelles from the cell (4).…”