Posted on 25 July 2023
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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: Sarcopenia is the age-related loss of muscle mass. Some amount of sarcopenia is inevitable with age, but it can be accelerated by muscle disuse. Muscle weakness is an important but often overlooked contributor to ageing and mortality, as it increases the risk of falls and fractures, reduces one’s ability to exercise, and worsens other age-related conditions such as diabetes.
A process called senescence is thought to be an important component of sarcopenia. Stem cells responsible for growing new muscle tissue enter a state called senescence, in which they are no longer able to divide. Metformin is a drug used to treat type II diabetes mellitus, but has many effects on the biology of ageing, including preventing cells from becoming senescent and enhancing the removal of cells that are senescent already. Metformin is perhaps the most heavily investigated drug with ‘anti ageing’ properties, though many are sceptical about its potential to affect human ageing.
What did the researchers do: In this study, researchers conducted a human clinical trial to test the effects of metformin on muscle atrophy caused by bed rest. They recruited 20 healthy older adults (aged 60 and above) who were physically active and did not have diabetes or other chronic diseases. They randomly assigned them to receive either metformin (up to 2g per day) or placebo for two weeks before and during five days of bed rest. They measured their muscle mass, strength, and function before and after the bed rest period. They also took muscle biopsies to analyse the molecular changes in their muscle cells.
Key takeaway(s) from this research: As hoped, metformin treatment was associated with a significant reduction in the loss of muscle mass during bed rest. The metformin group had more thick muscle fibres and fewer thin ones compared to the placebo group, though the total number of muscle fibres was unaffected. They also experienced less scarring of the muscle tissue and reduced expression of senescence markers in their muscle cells.
While this is great news, metformin was not a magic bullet for muscle health, as it did not prevent other aspects of muscle remodelling that occurred during disuse. For example, it did not prevent the accumulation of senescent CD8 T cells, a type of immune cell that accumulates during ageing and may impair muscle regeneration.
How can you apply this knowledge today: Metformin may one day be taken as a means to prevent sarcopenia and perhaps other age-related conditions. However, while metformin is a very safe drug, there’s not currently enough evidence to justify its use in this way, and you cannot buy it over the counter. Fortunately, there are many other strategies that are effective for preventing sarcopenia:
Disuse-induced muscle fibrosis, cellular senescence, and senescence-associated secretory phenotype in older adults are alleviated during re-ambulation with metformin pre-treatment https://doi.org/10.1111/acel.13936
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