# Reduced Proteasome Degradation of HSF‐1 Shifts Protein Stress Management With Age in Caenorhabditis elegans

## TL;DR

Aging worms adjust their protein stress responses by reducing the breakdown of HSF-1, helping them better handle chronic stress but lessening their response to sudden stress.

## Contribution

The study identifies PBS-7 as a key regulator of HSF-1 degradation, revealing an age-dependent mechanism for managing protein stress.

## Key findings

- Decreased PBS-7 binding in aged C. elegans reduces HSF-1 degradation.
- Increased HSF-1 enhances chronic stress responses by upregulating HSPs and autophagy genes.
- Upregulated HSPs suppress HSF-1 activation during acute stress like heat shock.

## Abstract

To maintain protein homeostasis, which is essential for health, animals have developed complex protective mechanisms against various acute and chronic stresses. However, the coordination of responses to these protein stresses, especially their age‐dependent changes, is not well understood. HSF‐1 is a key regulator of protein homeostasis. Our study identifies PBS‐7, a proteasome subunit, as its crucial regulator. In aged
C. elegans
, decreased PBS‐7 binding reduces proteasome‐mediated degradation of HSF‐1. The increase in HSF‐1 enhances responses to chronic stresses, like accumulating protein aggregates, by upregulating heat shock proteins (HSPs) and autophagy genes. Meanwhile, the upregulated HSPs suppress the activation of HSF‐1 upon acute stress, such as heat shock. Our findings reveal a mechanism that coordinates responses to acute and chronic protein stresses and highlights an adaptation prioritising protection against increasing protein aggregates in ageing.

Ageing
C. elegans
prioritises chronic protein stress protection over acute stress response by coordinating HSF‐1 activity. Decreased PBS‐7 binding in aged worms reduces HSF‐1 degradation, enhancing its ability to upregulate protective factors against accumulating protein aggregates while simultaneously suppressing its activation under acute heat shock.