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The NADase CD38 is induced by factors secreted from senescent cells providing a potential link between senescence and age-related cellular NAD+ decline.

Ever since I learned that CD38 expression seems upregulated with aging, and its activity seems to be an important cause of the age-related decline in NAD+ with age, I have wondered: why does CD38 get upregulated? This study may have an answer to this question. This group reports that SASP factors secreted by senescent cells can upregulate CD38 in non-senescent cells. So one might suspect that serum NAD+ would increase after a round of senolytic treatment. I wonder whether anyone has assessed for that potential outcome after senolytics.
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NAD+ supplementation rejuvenates aged gut adult stem cells.

This group reported that nicotinamide riboside could "rejuvenate" intestinal stem cells from aged mice and "reverses an impaired ability to repair gut damage". Interestingly, it appears that mTORC1 inhibition (via rapamycin administration) could prevent this effect, suggesting that NAD+ restoration may work through increased mTORC1 activity to restore some tissues.
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Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle.

This looks like some remarkable regenerative effects caused by inhibiting an enzyme that is increased in aging and impairs NAD+ salvage. In the treatment group, the response to muscle injury seemed considerably increased: "muscle stem cell proliferation and fusion were elevated, supporting nearly 2-fold greater cross-sectional area and shifts in fiber size distribution; prolonged treatment post-injury further augmented myofiber regeneration evidenced by increasingly larger fiber cross-sectional area". Apparently the activity of this enzyme that impairs NAD+ salvage (NNMT) increases with age, so I presume it may be a contributor to the age-related decline in NAD+. I wonder why it increases with age in the first place.
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Nicotinamide Metabolism Modulates the Proliferation/Differentiation Balance and Senescence of Human Primary Keratinocytes.

There have been some reports that nicotinamide can affect human mortality from skin cancer (e.g. see PMIDs 22297641 and 28468736), and I presume NAD+ replenishment is at least of some interest to Methuselah and SRF. Here, this group reports that nicotinamide significantly affects differentiation and proliferation of different types of skin cells in cell culture, and these effects can be influenced by impairing nicotinamide's conversion to NAD+, suggesting that NAD+ might be involved in this association between skin cancer and nicotinamide.
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Poly(ADP-ribose) drives pathologic α-synuclein neurodegeneration in Parkinson’s disease.

I have corresponded with James Clement about the possibility that elevated PARP-1 activity may a primary cause of the decline of NAD+ during aging, because PARP-1 consumes NAD+ as a cofactor in its activity. This group reports that PARP-1 also apparently accelerates the formation of toxic alpha-synuclein, and in at least one model, PARP-1 inhibition or deletion could prevent alpha-synuclein toxicity. PARP-1 inhibition or deletion does not seem like an enduring solution, as it leaves us tinkering with metabolism instead of cleaning up damage. I do wonder why PARP-1 is upregulated during aging; perhaps if we address the cause of this upregulation, we could prevent these negative downstream effects.
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