Assessing Pentadecanoic Acid In Vitro

The work on pentadecanoic acid noted here is interesting, but should be taken with a grain of salt given that it is performed in vitro. In general, one should expect any given set of mechanisms in the cell to be associated with many different means of manipulation. It is interesting to see a fatty acid capable of touching on the same mechanisms as rapamycin, but remember that the ability to influence the same mechanistic targets does not necessarily translate to the same ability to produce a modest slowing of aging in animal studies. So the usual advice stands here, to wait for the animal studies before getting too excited.

The BioMAP Diversity PLUS system includes a series of independently run and industry-standard pharmacological assays routinely used to screen and compare molecules for activity profiles and clinical indications as well as safety. Specifically, the BioMAP Diversity PLUS system tests molecules across 12 primary human cell-based systems mimicking various disease states and measures the molecule's effects across 148 clinically relevant biomarkers at four doses. The resulting cell-based phenotypic profile enables valuable insights into potential clinical applications of a compound, as well as identifying shared key activities with other compounds of interest.

Pentadecanoic acid (C15:0), an odd-chain saturated fatty acid, has mounting evidence of being essential to supporting cardiometabolic and liver health. People with low circulating C15:0 concentrations have a higher risk of having or developing type 2 diabetes, heart disease, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis, as well as specific types of cancer. As an essential fatty acid, C15:0 should, by definition, support healthspan, and longevity. Further, C15:0 has mTOR-inhibiting and AMPK-activating activities shared with rapamycin and metformin, respectively. As such, we compared the primary human cell phenotypic profile of C15:0 with acarbose, metformin, and rapamycin using BioMAP Diversity PLUS to objectively evaluate common clinically relevant cell-based activities supportive of an expanded healthspan and lifespan. Based on our findings, we then reviewed the literature for further evidence of C15:0 as a longevity-enhancing nutrient.

At their optimal doses, C15:0 (17 µM) and rapamycin (9 µM) shared 24 activities across 10 cell systems, including anti-inflammatory (e.g., lowered MCP-1, TNFα, IL-10, IL-17A/F), antifibrotic, and anticancer activities, which are further supported by previously published in vitro and in vivo studies. Paired with prior demonstrated abilities for C15:0 to target longevity pathways, hallmarks of aging, aging rate biomarkers, and core components of type 2 diabetes, heart disease, cancer, and nonalcoholic fatty liver disease, our results support C15:0 as an essential nutrient with activities equivalent to, or surpassing, leading longevity-enhancing candidate compounds.

Link: https://doi.org/10.3390/nu15214607