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Longevity Briefs: Suppressing Inflammation To Treat Age-Related Frailty

Posted on 21 December 2021

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Inflammation is an essential component of our immune systems that helps protect our tissues against pathogens. Unfortunately, inflammation can be very disruptive if it occurs when it shouldn’t. Chronic inflammation is associated with most diseases of ageing and probably contributes to physical weakness in old age by interfering with the maintenance of muscle tissue. We have plenty of ways to suppress inflammation, but these also suppress the normal immune response. We may be able to develop more selective drugs that can supress specific parts of the immune system, minimising harmful effects and potentially reducing frailty in old age.

Skeletal muscle as potential central link between sarcopenia and immune  senescence - EBioMedicine
It is thought that increased inflammatory signals due to changing body composition and ageing of the immune system could contribute to muscle ageing.

What did the researchers do: Researchers developed a compound called MYMD-1 that reduces chronic inflammation by suppressing several important inflammatory molecules, most notably one called TNF-alpha, which is generally the first inflammatory molecule to increase when someone gets an infection. The responsible company, MyMD Pharmaceuticals, completed phase 1 human safety studies earlier this year, and has been simultaneousely continuing research in mice. While the results of these mouse studies haven’t been published yet, CSO Dr Adam Kaplin told Longevity Technology that the results have been promising. The study looked at the effect on lifespan in 19 month-old mice treated with either MyMD-1, rapamycin, or rapamycin and metformin (both drugs that have been reported to extend mouse lifespan) over a period of 13 months.

Key takeaway(s) from this research: According to Kaplin, mice treated with MyMD-1 showed a highly statistically significant increase in survival time, and also lost less muscle strength compared with mice treated with the other compounds. MyMD-1 distinguishes itself from other inhibitors of TNF-alpha in that it is small enough to enter the brain – other compounds, like antibodies against TNF-alpha, are too large to cross the blood-brain barrier.

Small phase 1 clinical trials in humans earlier this year did not raise any safety concerns, and MyMD Pharmaceuticals is now planning phase 2 trials that will use a higher dose of the drug. After an initial month-long safety test, there will be a six-month trial in which people showing signs of increased inflammation will receive the drug. The aim is to assess whether the treatment can shut down inflammation and protect against sarcopenia (age related muscle loss) in an at-risk group. Ageing is still not accepted as a disease by the FDA, and it isn’t possible to detect effects on longevity in a study this short, so it makes sense to study specific age-related pathologies like muscle loss in this scenario. If all goes well, we should see results during the first quarter of 2022.

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