AI Article Synopsis
- The naked mole rat (NMR) lives a really long time and doesn't get many age-related diseases, which makes scientists curious about how it does that.
- Researchers looked at special cells from NMRs and compared them with cells from other animals to understand why NMRs are so healthy as they age.
- They found that a protein called CD44 plays a big role in helping NMRs deal with stress in their cells, which might help them live longer, even without needing another substance called hyaluronan (HA).
Article Abstract
The naked mole rat (NMR) is the longest-lived rodent, resistant to multiple age-related diseases including neurodegeneration. However, the mechanisms underlying the NMR's resistance to neurodegenerative diseases remain elusive. Here, we isolated oligodendrocyte progenitor cells (OPCs) from NMRs and compared their transcriptome with that of other mammals. Extracellular matrix (ECM) genes best distinguish OPCs of long- and short-lived species. Notably, expression levels of CD44, an ECM-binding protein that has been suggested to contribute to NMR longevity by mediating the effect of hyaluronan (HA), are not only high in OPCs of long-lived species but also positively correlate with longevity in multiple cell types/tissues. We found that CD44 localizes to the endoplasmic reticulum (ER) and enhances basal ATF6 activity. CD44 modifies proteome and membrane properties of the ER and enhances ER stress resistance in a manner dependent on unfolded protein response regulators without the requirement of HA. HA-independent role of CD44 in proteostasis regulation may contribute to mammalian longevity.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591879 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2023.113130 | DOI Listing |
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