Genetic intervention prolongs lifespan, boosts immunity in mice

[TomBAvoider]

As one may suppose, intervention further upstream yield stronger results when it comes to aging, compared to trying to control downstream effects through drugs and the like. Here is one example:

 

http://www.nature.com/ncb/journal/vaop/ncurrent/full/ncb3342.html

 

Per2 induction limits lymphoid-biased haematopoietic stem cells and lymphopoiesis in the context of DNA damage and ageing

• Jianwei Wang,
• Yohei Morita,
• Bing Han,
• Silke Niemann,
• Bettina Löffler
• & K. Lenhard Rudolph
•  
• Nature Cell Biology (2016) doi:10.1038/ncb3342

Received 11 March 2015  Accepted 14 March 2016  Published online 18 April 2016   Abstract

Ageing-associated impairments in haemato-lymphopoiesis are associated with DNA damage accumulation and reduced maintenance of lymphoid-biased (Ly-biased) compared with myeloid-biased (My-biased) haematopoietic stem cells (HSCs). Here, in vivo RNAi screening identifies period circadian clock 2 (Per2) as a critical factor limiting the maintenance of HSCs in response to DNA damage and ageing. Under these conditions, Per2 is activated predominantly in Ly-biased HSCs and stimulates DNA damage signalling and p53-dependent apoptosis in haematopoietic cells. Per2 deletion ameliorates replication stress and DNA damage responses in haematopoietic cells, thereby improving the maintenance of Ly-biased HSCs, lymphopoiesis, and immune function in ageing mice without increasing the accumulation of DNA damage. Per2-deficient mice retain Batf/p53-dependent induction of differentiation of HSCs in response to DNA damage and exhibit an elongated lifespan. Together, these results identify Per2 as a negative regulator of Ly-biased HSCs and immune functions in response to DNA damage and ageing.