As compared to previous studies on sarcopenia which mostly relied on blood serum markers to detect a change in muscle function, this study differs by using actual muscle biopsy to detect the changes at the genetic expression level.
This in turn provides a more reliable measurement of changes in the muscle, Dr Neerja Karnani, one of the lead authors of the study and a senior principal investigator at Singapore Institute of Clinical Sciences (SICS) of the research told NutraIngredients-Asia.
“Dealing with muscle biopsies means that you can actually look into the muscle that is undergoing a change…It’s a much more reliable measure of the mechanism (of how sarcopenia develops.
“Whereas blood (samples) tells you the micronutrients that are changing, the lipids in the muscles that are changing…It gives you a picture of what could be potentially going on, however, its just a surrogate marker and you will not be able to know what exactly is happening within the muscle,” Dr Karnani said.
The findings, published in Nature Communications, were also contributed by researchers from the National University of Singapore, in collaboration with Nestle Research and the EpiGen Global Research Consortium.
The study compared the genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 men in their 60s to 80s from Singapore, Hertfordshire in UK, and Jamaica.
A common theme across all three populations who suffered from sarcopenia was the presence of mitochondria bioenergetic dysfunction in the skeletal muscle at the gene transcriptional level, she pointed out.
There was also downregulation of mitochondrial protein homeostasis (proteostasis) gene.
This leads to fewer mitochondria, reduced mitochondrial respiratory complex expression and activity in the sarcopenic muscle.
Another key point of the study also showed how NAD+ levels could be linked to sarcopenia, which was “not so discreetly seen” in previous research, she added.
NAD+ is critical for mitochondrial function, it acts as a sensor of cellular energy levels and regulating energy production.
Also, the research found that the patients’ lean mass of the skeletal muscle and grip strength are more closely associated with mitochondrial bioenergetics dysfunction.
Dr Karnani said sarcopenia affects about 10% of the population and with the impacts that it leads to, including a loss of grip strength, increased chances of fall and fractures, meant that it would lead to a lower quality of life.
“I think it is critical that we find ways of intervention and eliminate sarcopenia from the population or reduce it or slow it down...That is why we studied sarcopenia.”
The entire process of completing the study and publishing the paper took about three years.
Intervention and future study
The next step of the study would dive deeper into identifying the intervention methods that could manage sarcopenia effectively, said Dr Karnani.
In the present study, the researchers have pointed out that nutritional and pharmacological mitochondrial therapeutics should be considered for the management of sarcopenia.
For example, the intervention may be in the form of supplementing nutrients, or to stabilise the mitochondrial machinery through means that target the cardiolipin – a component of the mitochondrial membrane.
Other ways include physical exercise; promoting the elimination of the damaged mitochondria using the natural molecule urolithin A – a gut-microbial metabolite; or targeting energy sensors such as AMPK, PPARs, and sirtuins which converge on the PGC-1α signalling.
Source: Nat Commun 10, 5808 (2019)
Mitochondrial oxidative capacity and NAD+biosynthesis are reduced in human sarcopenia across ethnicities
Authors: Migliavacca, E., Tay, S.K.H., Patel, H.P. et al