Longevity Briefs: A Fatty Acid That Slows Ageing?

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: Of the many possible strategies for delaying the ageing process, one approach is to target molecular pathways within our cells known as nutrient sensing pathways. As the name suggests, these pathways sense the availability of nutrients and control the behaviour of the cell accordingly, initiating a survival and repair response when nutrients are scarce. 

AMPK and mTOR are key molecules involved in nutrient sensing, making them promising targets for slowing the ageing process. They are responsible for many of the longevity benefits of calorie restriction, and are also the main targets of some of our most promising candidate drugs for delaying ageing (immune modulator rapamycin and antidiabetic drug metformin). While these drugs both have well established safety profiles in humans, it is not easy for the average person to procure them, nor would it necessarily be a good idea given that their effects in healthy humans have not been extensively studied.

What did the researchers do: In this study, researchers compared the cellular effects of a specific fatty acid, called pentadecanoic acid (C15:0), with three well-known longevity-enhancing compounds: acarbose, metformin, and rapamycin. C15:0 is an odd-chain saturated fatty acid that is found in dairy products and some fish. C15:0 was chosen because previous studies suggested that it had beneficial effects on cardiometabolic, immune, and liver health, and that it activates AMPK while inhibiting mTOR (both of these effects being desirable from a longevity standpoint).

The researchers used human cell-based models to test the effects of different doses of C15:0 on markers of ageing and disease. These included 12 human cell systems that mimic various disease states, such as inflammation, fibrosis and cancer. They compared the effectiveness of C15:0 in reducing these markers to the effectiveness of three well studied longevity-enhancing candidates: rapamycin and metformin (mentioned previously) and acarbose, another antidiabetic drug.

Key takeaway(s) from this research:

• C15:0 had a similar effect on clinically relevant biomarkers of ageing when compared to rapamycin, with both compounds capable of inhibiting mTOR.
• C15:0 also shared some effects with metformin and acarbose.
• Meta-analyses suggest that C15:0 consumption is associated with improved general health and longevity in humans.

The researchers found that C15:0 and rapamycin had the most clinically relevant, dose-dependent activities among the four compounds. At their optimal doses, C15:0 and rapamycin shared 24 activities across 10 cell systems, including anti-inflammatory, antifibrotic, and anticancer activities. For example, C15:0 and rapamycin reduced levels of inflammatory molecules like IL-10 and TNF alpha. C15:0 also shared a lesser number of effects with metformin and acarbose. These included boosting glucose uptake by cells, a main mechanism of action of metformin and one that is of interest for the control of type II diabetes.

These findings are all consistent with previously published research in animal models. Studies also suggest that C15:0 consumption is associated with ageing-relevant health benefits in humans, including increased haemoglobin and reduced risk of heart disease.

Rapamycin is arguably our most promising longevity enhancing drug candidate. The optimal dose of C15:0 was about double that of rapamycin, but rapamycin is a rare compound discovered in bacteria on Easter island, while C15:0 is a fatty acid found naturally in many foods. Furthermore, since it is not a drug, it is easier to gain approval to study the general health benefits of C15:0 in humans.

How can we apply this knowledge today: This study suggests that C15:0 could be as good or even superior to leading drug candidates when it comes to modulating the ageing process, though its effects on the ageing process in humans needs further investigation. In the meantime, we can try to increase our intake of C15:0 by consuming more foods that contain this fatty acid. Some examples are butter, cheese, yoghourt, milk, salmon, and sardines. However, keep in mind that C15:0 seems to act by activating AMPK and inhibiting mTOR, while consuming more calories does the reverse. As always, we need to be careful about modifying our diet for the sake of a single compound if that modification also changes our calorie intake.