Friday Hope: Metformin II: Reversing the Aging Clock and Preventing Long COVID

Metformin, via Nrf2, may be one of the most important therapeutics we have in preventing and reversing Spike Protein disease/injury.

A new paper by Yang, et al., shows how Metformin reverses the aging clock. This may be one of the critical reasons why Metformin has been so effective in treating COVID/Spike Protein diseases and injuries. 

If we have learned anything about the Spike Protein of SARS-CoV-2, it is that it is an apparent master of advancing biological age on a systemic level. In November of 2021, I published a post demonstrating how the Spike Protein induces all Nine Hallmarks of Aging, as defined by Carlos López-Otín et al. In their landmark 2013 paper. 

Hallmarks of Aging and the Spike 
https://wmcresearch.org/hallmarks-of-aging-and-the-spike/ 

There is also abundant clinical evidence of this, from accelerating age-related macular degeneration: 

SARS-COV-2 spike protein promotes RPE cell senescence via the ROS/P53/P21 pathway 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9898700/ 

To causing senescence in human cells: 

SARS-CoV-2 causes senescence in human cells and exacerbates the senescence-associated secretory phenotype through TLR-3 
https://www.aging-us.com/article/203560/text 

To inducing cardiac fibrosis: 

The SARS-CoV-2 spike protein induces long-term transcriptional perturbations of mitochondrial metabolic genes, causes cardiac fibrosis, and reduces myocardial contractile in obese mice 
https://www.sciencedirect.com/science/article/pii/S221287782300090X 

And the list of diseases of the old goes on. 

Metformin has already been shown to reduce viral load of SARS-CoV-2 and to prevent the virus’ return. 

A team of University of Minnesota researchers found that metformin, a drug commonly used to treat diabetes, can decrease the amount of COVID-19 virus in the body and lower the chances of the virus coming back strongly after initial treatment. 

U of M study finds metformin reduces COVID-19 viral load, viral rebound 
https://med.umn.edu/news/u-m-study-finds-metformin-reduces-covid-19-viral-load-viral-rebound 

Metformin also reduces the likelihood of developing Long COVID by an astounding 41%. 

Outpatient treatment with metformin reduced long COVID incidence by about 41%, with an absolute reduction of 4·1%, compared with placebo. Metformin has clinical benefits when used as outpatient treatment for COVID-19 and is globally available, low-cost, and safe. 

Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial 
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00299-2/fulltext 

Though, of course, clinical studies need to be performed, I propose that Metformin may be able to reverse the accelerated aging induced by the Spike Protein. A paper just published provides clinical evidence that Metformin decelerates the aging clock in male monkeys. And it does so systemically (as does the Spike). 

Highlights 

• Metformin prevents brain atrophy, elevating cognitive function in aged male primates 

• Metformin slows the pace of aging across diverse male primate tissues 

• Metformin counterparts neuronal aging, delivering geroprotection via Nrf2 in male primates 

In a rigorous 40-month study, we evaluated the geroprotective effects of metformin on adult male cynomolgus monkeys, addressing a gap in primate aging research. The study encompassed a comprehensive suite of physiological, imaging, histological, and molecular evaluations, substantiating metformin’s influence on delaying age-related phenotypes at the organismal level. Specifically, we leveraged pan-tissue transcriptomics, DNA methylomics, plasma proteomics, and metabolomics to develop innovative monkey aging clocks and applied these to gauge metformin’s effects on aging. The results highlighted a significant slowing of aging indicators, notably a roughly 6-year regression in brain aging. Metformin exerts a substantial neuroprotective effect, preserving brain structure and enhancing cognitive ability. The geroprotective effects on primate neurons were partially mediated by the activation of Nrf2, a transcription factor with anti-oxidative capabilities. Our research pioneers the systemic reduction of multi-dimensional biological age in primates through metformin, paving the way for advancing pharmaceutical strategies against human aging. 

Metformin decelerates aging clock in male monkeys 
https://www.cell.com/cell/abstract/S0092-8674(24)00914-0 

What we may ultimately learn from this, is that it is the Spike’s ability, as I have previously demonstrated, to be a “ROS Rocket” that is the primary cause of all of its accelerated aging proclivity. Metformin may just be the silver bullet. We will discover the answer. 

Once again, we are gifted with a picture-perfect Autumn weekend here in Vermont. It is for days like these that I moved here (and to be close to Montreal!). I find this news about Metformin to be extremely encouraging. I hope other researchers, especially those with labs, will also see the Nrf2 connection and conduct appropriate studies. 

As always, thank you for your readership, dialogue and support. Blessings, health and happiness to everyone.