The resolvin D and E biogenesis pathway regulatessenescence and ageing
Ageing is considered as a process were molecular, cellular and tissular function is impaired. One classic cellular phenotype that increases during ageing is cellular senescence. Upon senescence, the cells stop proliferating and release a variety of cytokines, chemokines and extracellular vesicles. However, the implication of biomolecules derived from lipids such as resolvins are not well characterised in senescence and ageing. Here, we find that the resolvin E and D biosynthesis pathway is activated as observed by an increase in their corresponding receptors and enzymes implicated. Furthermore, knockdown of the resolvins E and D receptors impairs the induction of senescence. This pathway is conserved not only during senescence but also in fibroblasts derived from aged human individuals, aged mice and during other inflammatory responses. A metabolomics analyses shows an increase in different precursors of resolvins in senescence. In accordance with prior data, we find that small extracellular vesicles (sEV) isolated from young human donors ameliorate inflammation and the biogenesis of resolvins both in different cell models and in aged mice. In summary, here we present data showing that the resolvins biogenesis pathway is induced in ageing and cellular senescence.