Barts-MS rose-tinted-odometer: ★★★★★ (skoda baby pink Wednesday #cca49a)
Should we all be taking metformin? As you know metformin is being tested in a remyelination therapy trial in MS; it rejuvenates senescent oligodendrocyte precursors making them more likely to make myelin.
The biology of metformin is fascinating as it also activates NRF2 the master transcription factor for programmed cell survival, which downregulates NFKappa-B the master pro-inflammatory transcription factor. I was surprised to find this paper below which shows the anti-ageing effects of metformin are not only limited to the brain but the thymus and the immune system as well.
Please note that ketogenic diets and fumarates (dimethyl fumarate and diroximel fumarate) also transactivate NRF2 and are potentially anti-ageing. It is a great pity Biogen pulled the plug on the DMF secondary progressive MS trial. I think we should revisit fumarates in progressive MS in combination with other potential agents that target mechanisms that drive smouldering MS.
The question I have is that in addition to a ketogenic diet should we all start taking metformin like so many other biohackers* are doing?
*Biohacking, also known as human augmentation or human enhancement, is do-it-yourself biology aimed at improving performance, health, and wellbeing through strategic interventions.
Fahy et al. Reversal of epigenetic aging and immunosenescent trends in humans. Aging Cell. 2019 Dec;18(6):e13028. doi: 10.1111/acel.13028. Epub 2019 Sep 8.
Epigenetic “clocks” can now surpass chronological age in accuracy for estimating biological age. Here, we use four such age estimators to show that epigenetic aging can be reversed in humans. Using a protocol intended to regenerate the thymus, we observed protective immunological changes, improved risk indices for many age-related diseases, and a mean epigenetic age approximately 1.5 years less than baseline after 1 year of treatment (-2.5-year change compared to no treatment at the end of the study). The rate of epigenetic aging reversal relative to chronological age accelerated from -1.6 year/year from 0-9 month to -6.5 year/year from 9-12 month. The GrimAge predictor of human morbidity and mortality showed a 2-year decrease in epigenetic vs. chronological age that persisted six months after discontinuing treatment. This is to our knowledge the first report of an increase, based on an epigenetic age estimator, in predicted human lifespan by means of a currently accessible aging intervention.
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.