Salk Institute scientists announced on July 23 that targeting the enzyme acid ceramidase could offer a new approach to improving healthy aging and longevity. The research, published in Cell Death and Disease on July 10, explored how cellular processes such as senescence and ferroptosis contribute to age-related dysfunction.
The team found that elevated levels of acid ceramidase in senescent human lung cells increased their susceptibility to ferroptosis, a form of iron-dependent cell death. This vulnerability could also be transferred to neighboring cells. Experimental drugs that inhibit acid ceramidase have already been developed for other diseases, suggesting potential pathways for extending healthspan.
"Senescent cells are linked to many age-related conditions, including arthritis, poor wound healing, and neurodegenerative diseases like Alzheimer's or Parkinson's," said senior and co-corresponding author Pam Maher, PhD, a research professor at Salk. "Our findings are a big milestone in the ongoing public health effort to support healthy aging, as we now have a novel target for developing new therapeutics that could be applied to a multitude of diseases and disorders."
First author David Soriano-Castell, PhD, said, "This is an entirely novel pathway that is independent of the mechanisms usually associated with ferroptosis-induced cell death, as it doesn't involve any changes in iron or glutathione levels but instead modulates the lipid metabolism." Soriano-Castell added, "We have unraveled a new mechanistic connection between ferroptosis and senescence. This gives us a clear target that would eliminate two birds with one stone, eliminating senescent cells and keeping neighboring cells healthy for longer."
Maher originally discovered the cellular pathway now known as ferroptosis in 2001. Recent studies from her lab have reinforced links between ferroptosis and neurodegenerative diseases such as Alzheimer's and Parkinson's disease.
Soriano-Castell said, "This is only the beginning. The next step is finding a more complete pathway and translating into animals and tissues, then clinical trials of our own... But what is important is that acid ceramidase is targetable." Maher concluded, "The more we learn about ferroptosis...the more possibilities there are for healthy aging innovations."
