A new Aging Cell study treated naturally aged 17-month-old female mice with the GPR40 agonist GW9508 every other day for one month.
The lowest dose produced an approximately 50% higher thymic index versus aged controls. More importantly, GW9508 increased proliferating cortical and medullary thymic epithelial cells, all thymocyte developmental stages, naïve T cells, and cells phenotypically classified as recent thymic emigrants. The effects were largely antagonized by the GPR40 blocker GW1100.
This appears to be more than simple preservation and is consistent with partial thymic re-expansion. However, true regrowth was not formally proven because there was no pre-treatment cohort, young control for the main endpoints, treatment washout, TREC/TCR-diversity analysis, or infection/vaccine challenge.
Mechanistically, GPR40 activation increased intracellular calcium and AMPK while suppressing chronic ERK1/2-MAPK hyperactivation in senescent thymic epithelial cells.
Interesting signal, but still a small study: approximately five mice per group, females only, and GW9508 remains a preclinical research compound.