Considering Proteostasis and Aging

Proteostasis is the normal maintenance of protein levels and protein structure in a cell. This is disrupted with age, the result of failing quality control, epigenetic change, and other issues. Loss of proteostasis is a hallmark of aging, but has the look of a consequence of aging, not a cause to be addressed. It is also highly complex, and thus progress towards practical therapies is probably better served by a focus on causes of aging rather than the fine details of age-related changes in the cell. Fix the causes, see how well those repair efforts improve long-term health, and then worry about the fine details of the biochemistry of aging. Proteostasis is the sum of reactions and signalling pathways related to the synthesis, folding, trafficking, disaggregation, and degradation of proteins. One of the hallmarks of aging is a decline in proteostasis. Unsurprisingly, defects in all major steps of proteostasis are related to the accumulation of toxic aggregates and misfolded proteins, a key feature of neurodegenerative diseases. Throughout evolution, a range of protein quality-control mechanisms have emerged, some of which are specialised in monitoring the proteome within specific subcellular compartments. Examples are the cytosolic heat-shock response (HSR), the mitochondrial unfolded protein response (UPRmt), and the unfolded protein response of the endoplasmic reticulum (UPRER). The mechanisms underlying age-related proteostasis collapse are still not completely un...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs