Lowering body temperature extends longevity in various organisms. This study investigates the mechanism behind cold-induced longevity and its effects on protein aggregation, a hallmark of neurodegenerative disorders. Researchers found that cold temperatures selectively induce the trypsin-like activity of the proteasome in *C. elegans* through PSME-3 (PA28γ ortholog). PSME-3 is crucial for cold-induced longevity and improves protein degradation. Cold-induced PSME-3 also reduces protein aggregation in *C. elegans* models of Huntington's and ALS. Similarly, moderate cold temperatures in human cells activate trypsin-like activity via PA28γ/PSME3, reducing aggregation and neurodegeneration. This research suggests a conserved beneficial role of cold temperature in proteasome regulation with implications for aging and age-related diseases.

Hyun Ju Lee, Hafiza Alirzayeva, Seda Koyuncu, Amirabbas Rueber, Alireza Noormohammadi, David Vilchez