Boosting NAD+ delays stem cell senescence and reprograms aged somatic cells

Stem cell therapy research is becoming increasingly popular with results to show. In clinical trials, the use of mesenchymal stem cells (MSCs) from tissues, such as bone marrow, umbilical cord blood, and adipose tissue, has been approved for the treatment of incurable diseases. For creation of these therapies there are two main sources of stem cells: multipotent adult stem cells (ASCs), which are found in adult tissues, and pluripotent stem cells (PSCs), which are found in embryonic tissues. Recent developments in somatic cell reprograming technology have led to the creation of induced PSCs (iPSCs) as an alternative source for embryonic stem cells (ESCs).

One of the challenges is that the individuals considering undergoing stem cell therapy are often aged or suffering from age‐related degeneration, and the quality of cells collected from such individuals as sources for transplantation or iPSC generation cannot be guaranteed. The large‐scale expansion of ASCs for clinical use is challenging, as cellular senescence leads to loss of self-renewal capacity and multipotency.

This led a research team from the Stem Cell Research Center (KRIBB) in Korea to investigate the mechanisms that underlie senescence and rejuvenation during aged cell reprogramming in order to identify factors that can overcome these age‐associated problems. The research started from the observation they made that enzymes, such as NNT and NMNAT3, that control mitochondrial NAD+ levels appear to be susceptible to aging. And that aged tissues, exhibiting low mitochondrial NAD+ levels and accompanying decreases in SIRT3 activity, create a barrier to cell fate transition.

They setup an experiment in which aged mice groups were genetically altered to over-express NNT and NMNAT3 and as result exhibited higher levels of NAD+. Importantly when the researchers extracted cells of these genetically altered mice they noticed that the recovery of mitochondrial NAD+ levels by NNT or NMNAT3 overexpression led to improved reprogramming efficiency of aged somatic cells and extention of the lifespan of MSCs by delaying replicative senescence. The researchers concluded that these results demonstrate that maintenance of mitochondrial NAD+ levels is critical for reversing the mechanisms of aging and ensuring that cells collected from aged individuals are of high quality.

While this study was meant to create methods to extract healthier cells from the body to increase success of stem cell therapies the result also indicates that maintaining or recovering NAD+ levels leads to healthier cells inside the body. This adds to findings of another recent study which also observed that repletion of NAD+ delays senescence of stem cells. In that study the mice were fed with a diet containing Nicotinamide Riboside.

You can find the study here.

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