Increasing serotonin (5-HT) breakdown delays/prevents aging – To Extract Knowledge from Matter

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• A much simpler explanation for the exception NMR longevity may be the fact that those rodents live in deep burrows that they almost never leave, and as such are chronically exposed to CO2 ambient concentrations that are many-fold higher than the CO2 exposure of the common rat.

• One of the results of breathing high-CO2 air is increased uptake and degradation of serotonin (5-HT).

• Aside from 5-HT having a known role in chronic diseases, the study below now demonstrates that 5-HT may also have a crucial role in aging – i.e. it is the uniquely upregulated degradation of 5-HT in the NMR that prevents the accumulation of senescent (old) cells, thus largely preventing the “old” phenotype in these animals regardless of their age.

• Aside from increasing endogenous CO2 levels, other interventions that may achieve the same effect in humans is intake of substances known to upregulate the activity of the monoamine-oxidase type A (MAO-A) enzyme discussed in the study. Such substances are vitamin B2 (riboflavin), copper, magnesium, progesterone, and androgens. Obviously, reducing 5-HT synthesis is probably an even better approach, and can be achieved by avoiding dietary tryptophan and/or inhibiting its absorption from the GI tract. Gelatin and aspirin are probably the most appropriate interventions for addressing the tryptophan angle.

• “natural senolytic” or senescent cell-removal mechanism in NMRs, involving serotonin metabolism

• “Senolysis or the targeted removal of senescent cells has been shown to inhibit aging-related decline in mice.””

• Upon senescence induction, in NMR cells, serotonin was metabolized by monoamine oxidase

• (MAO; an enzyme highly activated in senescent NMR fibroblasts after induction of cellular senescence) and converted to 5-hydroxyindole acetic acid (5-HIAA; a metabolite), releasing large amounts of hydrogen peroxide (H2O2). The team proposed that oxidative stress due to the intracellular production of H2O2 predisposed the senescent NMR fibroblasts to the cell death pathway, thus leading to senolysis (selective removal of senescent cells). This was confirmed by the observation that the addition of MAO inhibitors and antioxidants inhibited cell death in NMR fibroblasts.”

• “…Furthermore, treatment with the MAO inhibitor significantly suppressed cell death but increased the number of senescent cells only in NMR lung on day 21. This suggests that MAO plays a role in inducing cell death and reducing the number of senescent cells following the induction of cellular senescence in NMR lung cells. These results are consistent with the in vitro findings and suggest that MAO contributes to suppress the accumulation of senescent cells in NMR tissues.”