Combination therapy could delay sarcopenia-related muscle loss

Wanting to stay as fit and healthy as possible while we age is a given, but as we get older, the body degrades, our muscles shrink and strength declines. Some older people suffer from excessive muscle loss, a debilitating condition known as sarcopenia. University of Basel researchers have shown that a combination therapy could delay the onset of sarcopenia.

Longevity.Technology: We are now living longer than ever before, but has there been an associated upswing in how healthily we are living? In order to make the most of the extra years we now have, it is important to remain as healthy, mobile and independent as we can. While time may be on our side, our bodies might not necessarily be, with our muscles inevitably losing mass and strength. This age-related muscle loss puts an end to an autonomous lifestyle for many elderly people, who must then rely on family or the healthcare system for daily support, rather than aging in place, as 90% wish to do [1].

Slowing age-related muscle loss

“Age-related muscle decline already occurs in our thirties but begins to accelerate at around 60. By age 80, we have lost about a third of our muscle mass,” says Dr Daniel Ham, one of the lead authors of the study published in Nature Communications. “Although this aging process cannot be stopped, it is possible to slow it down or counteract it, for example through exercise [2].”

Researchers led by Professor Markus Rüegg at the Biozentrum of the University of Basel have demonstrated in mice that both calorie restriction and the drug rapamycin have a positive effect on aging skeletal muscle. “If we can understand what happens in the muscle as we age, perhaps we can design treatments to counteract muscle aging and prevent sarcopenia,” he says [2].

“Both calorie restriction and rapamycin have been proposed as anti-aging interventions, but we didn’t expect the two treatments to provide additive benefits,” explains Dr Nitish Mittal, another lead author of the study [2].

READ MORE: Focus on frailty – new senolytic holds potential for sarcopenia treatment

Previously, it was thought that moderate fasting and rapamycin represent different means of achieving the same goal – namely, suppression of the protein complex mTORC1, which accelerates aging when overactive.

Getting the best of both

“Contrary to our expectations, the treatments do not redundantly converge at mTORC1,” emphasises Ham. “While we could understand that calorie restriction would have beneficial effects beyond mTORC1 suppression, it was incredibly surprising to us that rapamycin, an mTORC1 inhibitor, further slowed muscle aging in calorie restricted mice, where mTORC1-activating nutrients are available for just a few hours each day [2].”

This means that in calorie-restricted mice that had been treated with rapamycin, the beneficial effects were additive, with mice displaying significantly better muscle function than mice receiving either treatment alone [3]. “Compared to their peers, treated mice are more active and physically capable because their muscles remain healthy,” says Ham [2].

Healthy muscles foster longer independence

“The health of our muscle really is wealth. Beyond physical function, muscles are essential for whole-body metabolism and the proper functioning of many organs,” says Mittal [2].

The positive impact of calorie-restricted diets and rapamycin on muscle aging begs an intriguing question – can people suffering from sarcopenia profit from a combined therapy consisting of an mTORC1 inhibitor, a calorie restriction-mimicking drug and perhaps exercise?

The authors of the paper believe they can. “We conclude that rapamycin and calorie restriction exert distinct, compounding effects in aging skeletal muscle, thus opening the possibility of parallel interventions to counteract muscle aging,” they conclude [3].

“Strong and healthy muscles provide many benefits for elderly people, in fact for all of us,” says Ham. “We can live an active and independent life for longer, and enjoy activities such as hiking, traveling or taking care of the grandkids [2].”

Not only would improved strength and muscle function improve life quality and healthspan, but it would play a part in significantly reducing the burden on relatives and healthcare systems.

READ MORE: Aging in place: technologies to live long and independently

[1] https://longevity.technology/aging-in-place-technologies-to-live-long-and-independently/
[2] https://www.unibas.ch/en/slowing-age-related-muscle-wasting.html
[3] https://www.nature.com/articles/s41467-022-29714-6

Photograph: Anna Shvets/Pexels

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