'Increased NAD+ metabolism may enhance secretory activity of senescent cells in a way that promotes tumor progression'

https://medicalxpress.com/news/2019-02-insight-tumor-suppressive-tumor-promoting-effects-cellular.html

The report on the study here has me re-examining my NR usage, as someone in their early 30s who isn't at the point of NAD+ decline.

Has there been further commentary on the risks highlighted with this study? Any practical recommendations in light of it?

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  • the first logical step is to fokus on removing senescent cells before starting NAD+ therapy. it is senescent cell that "may" promote cancer proliferation. (At least in in vivo mouse models). 

     

    " Cellular senescence is a process in which cells irreversibly stop dividing and represents a potent tumor suppressive mechanism. At the same time, senescent cells also produce a variety of inflammatory soluble molecules that can promote tumor growth, known by the name of senescence-associated secretory phenotype (SASP).

    The laboratory of Rugang Zhang, Ph.D., deputy director of The Wistar Institute Cancer Center, professor and co-program leader of the Gene Expression and Regulation Program, investigated the role of a family of proteins called HMGAs in cellular senescence and the SASP.

    HMGAs are DNA-binding proteins that regulate gene expression. They are frequently overexpressed and associated with poor prognosis in many cancer types, yet they are known to promote senescence. This new research aims to clarify these mechanisms to unveil the dual role of the HMGA family of proteins in cancer.

    Zhang and colleagues discovered that in cells undergoing senescence HMGAs increase the levels of NAMPT, a key enzyme in the production of nicotinamide adenine dinucleotide (NAD+), a cellular factor critical for metabolism and enzyme function. Importantly, increased NAD+ levels enhanced the SASP.

    "Our data show that NAD+ levels influence the secretory activity of senescent cells in a way that may promote tumor progression," said Zhang. "It is well documented that cellular NAD+ concentrations decrease during aging and the use of NAD+ supplementation is being studied as a new preventive opportunity for aging and age-associated disorders. Our results may have far-reaching implications on this field of investigation."

    In fact, by manipulating the expression of HMGA1 and NAMPT, the researchers observed that increased NAD+ metabolism promotes cancer cell proliferation and progression in vivo in mouse models of pancreatic and ovarian cancers."

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