Experimental cell researchJan 12, 2021

The decline of protein maintenance with aging from worms to humans

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 28, 2026

Abstract

A decline in proteostasis is associated with cellular senescence in human cells as they age.

Aging cells exhibit a failure to respond effectively to stress, contributing to proteostasis collapse.
Cellular senescence involves the accumulation of cells that resist death and promote inflammation.
The decline in proteostasis may result from reduced activation of stress-response pathways.
Impairments in proteasome function also contribute to the decline in proteostasis during aging.
Potential mechanisms include decreased chromatin dynamics and compromised nuclear integrity.

Simplified

The aging proteostasis decline manifests in a failure of aging cells and organisms to properly respond to proteotoxic challenges. This proteostasis collapse has long been considered a hallmark of aging in nematodes, and has recently been shown to occur also in human cells upon entry to senescence, opening the way to exploring the phenomenon in the broader context of human aging. Cellular senescence is part of the normal human physiology of aging, with senescent cell accumulation as a prominent feature of aged tissues. Being highly resistant to cell death, senescent cells, as they accumulate, become pro-inflammatory and promote disease. Here we discuss the causes of human senescence proteostasis decline, in view of the current literature on nematodes, on the one hand, and senescence, on the other hand. We review two major aspects of the phenomenon: (1) the decline in transcriptional activation of stress-response pathways, and (2) impairments in proteasome function. We further outline potential underlying mechanisms of transcriptional proteostasis decline, focusing on reduced chromatin dynamics and compromised nuclear integrity. Finally, we discuss potential strategies for reinforcing proteostasis as a means to improve organismal health and address the relationship to senolytics.

Full Text

We can’t show the full text here under this license.

View Full Text ↗

The decline of protein maintenance with aging from worms to humans

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief