Cold temperatures activate a cellular mechanism that breaks down dangerous proteins which cause problems associated with aging, according to a study published in Nature Aging.
Researchers already knew that life expectancy increases when animals are kept at low temperatures. This applies not only to cold-blooded animals like worms, flies, or fish but also to warm-blooded mammals (including humans). For example, with mice, even a small drop in body temperature (just 0.5C) is enough to extend their lifespan. However, the mechanism behind this process has been a mystery until now. A team from the University of Cologne’s CECAD Cluster of Excellence in Aging Research in Germany has now unlocked a mechanism to explain this effect.
The researchers used a non-vertebrate model organism — nematode Caenorhabditis elegans — and human cells cultivated in vitro. Both included genes for neurodegenerative diseases common in older patients, amyotrophic lateral sclerosis (ALS), and Huntington’s disease, which are characterised by an accumulation of harmful protein deposits. In both cases, low temperatures eliminated these protein clumps.
To find out more about the exact mechanism, the team assessed the activity of proteasomes which are involved in removing damaged proteins from cells. Results showed that low temperatures activated these structures and led to more efficient removal of dangerous proteins. “Taken together, these results show how over the course of evolution, the cold has preserved its influence on proteasome regulation – with therapeutic implications for aging and aging-associated diseases,” said Professor David Vilchez.
The risk for neurodegenerative diseases — associated with the accumulation of protein clumps — increases with age. Examples include Alzheimer’s, Parkinson’s, Huntington’s, and ALS. “We believe that these results may be applied to other age-related neurodegenerative diseases as well as to other animal species,” said Vilchez.
An interesting finding was that the proteasome activity could be increased by genetically overexpressing the components, which helps to eliminate protein clumps even at normal body temperatures. The authors hope these results can be used in the future to develop new treatments to prevent age-associated diseases.
Lee, H.J., Alirzayeva, H., Koyuncu, S. et al. Cold temperature extends longevity and prevents disease-related protein aggregation through PA28γ-induced proteasomes. Nat Aging (2023). https://doi.org/10.1038/s43587-023-00383-4