Dietary restriction ameliorates haematopoietic ageing independent of telomerase, whilst lack of telomerase and short XXXX exacerbates the ageing phenotype.

@entity10205 @entity19 @entity409 @entity15087 @entity21324
Ageing is associated with an overall decline in the functional capacity of tissues and stem cells, including haematopoietic stem and progenitor cells (HSPCs), as well as @entity409 . Dietary restriction (DR) is a recognised anti-ageing intervention that extends lifespan and improves health in several organisms. To investigate the role of @entity10205 and telomerase in haematopoietic ageing, we compared the HSPC profile and clonogenic capacity of bone marrow cells from wild type with telomerase-deficient @entity19 and the effect of DR on these parameters. Compared with young @entity19 , aged wild type @entity19 demonstrated a significant accumulation of HSPCs (1.3% vs 0.2%, P=0.002) and elevated numbers of granulocyte/macrophage colony forming units (CFU-GM, 26.4 vs 17.3, P=0.0037) consistent with myeloid "skewing" of haematopoiesis. DR was able to restrict the increase in HSPC number as well as the myeloid "skewing" in aged wild type @entity19 . In order to analyse the influence of short @entity10205 on the ageing phenotype we examined @entity19 lacking the RNA template for telomerase, @entity21324 (-/-). Telomere shortening resulted in a similar bone marrow phenotype to that seen in aged @entity19 , with significantly increased HSPC numbers and an increased formation of all myeloid colony types but at a younger age than wild type @entity19 . However, an additional increase in erythroid colonies (BFU-E) was also evident. @entity19 lacking telomerase reverse transcriptase without shortened @entity10205 , @entity15087 (-/-), also presented with augmented haematopoietic ageing which was ameliorated by DR, demonstrating that the effect of DR was not dependent on the presence of telomerase in HSPCs. We conclude that whilst shortened @entity10205 mimic some aspects of haematopoietic ageing, both shortened @entity10205 and the lack of telomerase produce specific phenotypes, some of which can be prevented by dietary restriction.
