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basmwklz OP t1_j7a7om4 wrote

Abstract: >Flavin containing monooxygenases (FMOs) are promiscuous enzymes known for metabolizing a wide range of exogenous compounds. In C. elegans, fmo-2 expression increases lifespan and healthspan downstream of multiple longevity-promoting pathways through an unknown mechanism. Here, we report that, beyond its classification as a xenobiotic enzyme, fmo-2 expression leads to rewiring of endogenous metabolism principally through changes in one carbon metabolism (OCM). These changes are likely relevant, as we find that genetically modifying OCM enzyme expression leads to alterations in longevity that interact with fmo-2 expression. Using computer modeling, we identify decreased methylation as the major OCM flux modified by FMO-2 that is sufficient to recapitulate its longevity benefits. We further find that tryptophan is decreased in multiple mammalian FMO overexpression models and is a validated substrate for FMO-2. Our resulting model connects a single enzyme to two previously unconnected key metabolic pathways and provides a framework for the metabolic interconnectivity of longevity-promoting pathways such as dietary restriction. FMOs are well-conserved enzymes that are also induced by lifespan-extending interventions in mice, supporting a conserved and important role in promoting health and longevity through metabolic remodeling.


UndercoverProphet t1_j7a8tyq wrote

I wish I understood what this means and how I could use it to my benefit. I’m more versed in psychology and chemistry than biology or biochemistry.


Mock333 t1_j7abkum wrote

Get FMOs inside of you, and you might live healthier/longer.

That was my understanding.


Darkhorseman81 t1_j7aqa1w wrote

Balance between NO2 and H2S helps regulate epigenetic quality control. This plays a role in regulating them and the transulferation pathways.

It's FAD dependent. So, essentially, eat your riboflavin / Vitamin B2, it's as important as that faddish NMN that the longevity Influencers are going on about.

Probably more so, as this backends on to NAD+ salvage pathway dysfunction.

Might eliminate the need for NAD precursors for longevity outside of normal diet.


Darkhorseman81 t1_j7aq1sd wrote

This is useful. At least now I know more about how riboflavin feeds into one carbon and transulferation pathways. Why FAD is as important as NAD.

This may be a backend of why dysregulation of transulferation pathways speed up aging, and why certain transulferation gene variants have much longer lifespans.

It ties in metabolism of NO2 for Nucleotides, h2s for transulferation, and one carbon, and why they should be kept in balance.

Touches on epigenetic quality control.


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PlantingMatters t1_j7amxfj wrote

Practice calorie restriction and live a longer life.