Neurodegenerative diseases such as Alzheimer’s disease or Huntington’s disease are characterized by the pathological and toxic accumulation of misfolded proteins into protein aggregates. Previous work from the Jakob Lab has demonstrated that specific changes to the epigenetic landscape early in life result in improved organismal fitness later in life and a longer lifespan. However, whether these early life epigenetic alterations affect pathologies that occur in neurodegenerative diseases, and what molecular players are involved in mediating these beneficial effects, remains unclear.
In a new study recently published in Nature Aging, Oleson et al. demonstrate that early-life modifications to the C. elegans epigenetic landscape protect animals against the toxic effects of misfolded proteins later in life. The authors find that the protective actions of these epigenetic modifications are conferred by a substantial increase in the protein heat shock factor 1 (HSF-1), a longevity factor known to act predominantly during C. elegans development. Interestingly, these beneficial effects utilize a distinctive mode of HSF-1 signaling which involves significant alterations to the composition of C. elegans lipids and their metabolism. Together, these findings provide a fresh perspective on links between the epigenetic landscape, HSF-1 activity and lipid metabolism and shed new light on what molecular processes could be targeted to protect against toxicity seen in neurodegenerative diseases.
Oleson, B.J., Bhattrai, J., Zalubas, S.L. et al. Nat Aging (2023).
