2020/11/13 - metformin and rapamycin for aging - arginine for inhibiting protein agregation

 

Some news on metformin - a study of C. elegans (worms) and human cell cultures found that older individuals had deleterious effects while younger individuals benefited. Co-administering rapamycin alleviated the toxic effects in older individuals:

https://medicalxpress.com/news/2020-11-age-decisive-positive-negative-effects.html  

Original research article: https://doi.org/10.1038/s42255-020-00307-1

I am curious to know if boosting NAD+ would also mitigate the toxicity. Related:

https://www.sciencedaily.com/releases/2018/12/181211113024.htm

Coincidentally I also saw yesterday a video presentation on the effects of aging on microRNA production in response to exercise. An enzyme called DICER is involved in RNA processing and it increased in activity in response to exercise; the effect size was found to be much lower in older individuals and the effect is AMPK dependent.

https://youtu.be/lN_wJT-EkuA

10:54 there's one young individual at the bottom of the graph - what's up with that? 

~

There's some work on arginine inhibiting protein aggregation, mostly in relation to spinocerebellar ataxia, but also some on a-syn/Parkinson and I hope to read more. Some SCA patients are trying arginine as a supplement but I wonder if citrulline or ornithine would induce a more sustained increase in arginine levels and be more effective.

Agmatine may have similar protein aggregate inhibiting activity and also inhibits iNOS; it is apparently used as a recreational drug at very high doses and has similar effects to ketamine. It is found in Japanese sake: https://pubmed.ncbi.nlm.nih.gov/9339564/

"Agmatine holds the key to prevent the toxic effects associated with induction of NO synthesis by its ability to inhibit inducible nitric oxide synthase."

https://pubmed.ncbi.nlm.nih.gov/14998549/ [ paywalled article ] 

Makes me wonder about the sex ratio flip in PD rates in Japan; I would guess men drink more sake than women.

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