CASIN Alters Epigenetic State to Produce Lasting Improvement in Aged Stem Cell Function

We report that after CASIN treatment aged MuSCs divisional kinetic and myogenic capacity in vitro are enhanced and, after injuring the muscle in vivo, tissue regeneration is improved. Supporting that the MuSC improvement after CASIN might contribute to extend mouse healthspan, CASIN mice performed better than aged control mice in endurance and strength tests in steady-state and also after damage. Moreover, we report on systemic CASIN affecting Cdc42 and tubulin polarity as well as H4K16ac epigenetic polarity in aged HSCs. The data on H4K16ac obtained by histological analyses of whole mount bone marrow sections aligns to those previously reported on the DNA-methylation-based epigenetic clock and strongly support at least some traits of epigenetic rejuvenation in HSCs after systemic CASIN treatment. Furthermore, the histological analysis shows an intriguing effect of CASIN also on aged HSC localization, which after the treatment is closer to arteries and endosteum, like young blood stem cells. At the transcriptional level, stress response, and inflammation constitute the major signaling pathways targeted by CASIN in vivo. Consistently, we have previously reported a significant reduction in the levels of inflammatory cytokines (IL1α, IL1β, and INFγ) in peripheral blood serum of aged mice after in vivo CASIN treatment. These same cytokines were also shown by others to play critical roles in aging of the blood and other tissues The hematopoietic system is the carr...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs