Longevity Briefs: An Amino-Acid Mix May Replicate The Benefits Of Collagen

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.

The problem:

Collagen supplements are gaining popularity for their advertised benefits for healthy ageing, particularly for skin and joint health. Collagen is a structural protein that forms the major component of the extracellular matrix – the protein mesh that exists between cells and holds them together. Collagen production declines with advancing age, hence the idea that collagen supplementation may be able to help counteract this change and promote healthy ageing. There might be some truth to this, but as with many dietary supplements, the marketing claims about the health benefits of collagen often go far beyond what has actually been shown in human clinical trials.

Most collagen is absorbed by the gut only after having been broken down into its constituent amino-acid building blocks. There’s no guarantee that these amino acids will actually be used to build more collagen. On the flip side, it might be possible to replicate the benefits of collagen supplementation simply by delivering a few key amino acids. In this study, researchers investigated the ‘minimal required unit’ of ingested collagen to replicate some of the previously reported benefits.

The discovery:

The team discovered that a specific mix of collagen’s main amino acids – three parts glycine to one part proline to one part hydroxyproline – was sufficient to trigger benefits across multiple species.

Arriving at the above amino acid ratio was fairly straightforward, as these are the three most common amino acids in collagen, with glycine being roughly three times more common than the other two. They first tested this ratio in C. elegans worms and found that it resulted in increased collagen production and a 6–27% increase average (mean) lifespan across multiple trials. They then treated human skin cells with the same ratio and observed rapid upregulation of collagen and extracellular‑matrix genes.

Next they tested the same ratio in mammals: 20 mice aged 20 months (roughly equivalent to a human in their 60s) were fed the mix at a modest dose (100mg per kg of body weight) for 6 months as part of their diet. Researchers observed that the treated mice had significantly reduced visceral fat and improved grip strength in comparison to control mice who continued to be fed a standard diet without the additional amino acids.

Finally, researchers conducted a preliminary open‑label human study (participants knew what they were taking and there was no placebo group to serve as a control). 66 healthy adults took a “Collagen Activator” (the 3:1:1 mix plus vitamin C, astaxanthin and calcium‑alpha‑ketoglutarate, all of which have been found to modulate collagen production in past studies) daily for 6 months. Skin features such as hydration, elasticity and cosmetic appearance improved within 3 months and average (mean) epigenetic age measured from saliva samples (and therefore mainly epithelial cells and white blood cells) fell by about 1.4 years over the course of 6 months.

The implications:

This study suggests that there is a specific amino‑acid ratio that can prompt cells to boost collagen production and perhaps slow some markers of ageing. However, these findings should be treated as preliminary for the moment, as the most important part of the study (in which the effect in humans was tested) didn’t include a placebo control group. The animal findings also need to be treated with some caution, since this part of the study also had a limitation that the authors acknowledged: the mice receiving the control diet were not fed a different set of supplementary amino-acids, but instead received no amino-acids at all. This means that some of the effects observed in the treatment group could simply have been due to the mice receiving more amino-acids in their diet.