Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Pentadecanoic Acid (C15:0), an Essential Fatty Acid, Shares Clinically Relevant Cell-Based Activities with Leading Longevity-Enhancing Compounds

Version 1 : Received: 8 October 2023 / Approved: 9 October 2023 / Online: 9 October 2023 (10:53:44 CEST)

A peer-reviewed article of this Preprint also exists.

Venn-Watson, S.; Schork, N.J. Pentadecanoic Acid (C15:0), an Essential Fatty Acid, Shares Clinically Relevant Cell-Based Activities with Leading Longevity-Enhancing Compounds. Nutrients 2023, 15, 4607. Venn-Watson, S.; Schork, N.J. Pentadecanoic Acid (C15:0), an Essential Fatty Acid, Shares Clinically Relevant Cell-Based Activities with Leading Longevity-Enhancing Compounds. Nutrients 2023, 15, 4607.

Abstract

Pentadecanoic acid (C15:0) is an essential odd-chain saturated fatty acid with broad activities relevant to protecting cardiometabolic, immune, and liver health. C15:0 activates AMPK and inhibits mTOR, both of which are core components of the human longevity pathway. To assess the potential for C15:0 to enhance processes associated with longevity and healthspan, we used human cell-based molecular phenotyping assays to compare C15:0 with three longevity-enhancing candidates: acarbose, metformin, and rapamycin. C15:0 (n=36 activities in 10 of 12 cell systems) and rapamycin (n=32 activities in 12 of 12 systems) had the most clinically relevant, dose-dependent activities. 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, TNFɑ, 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.

Keywords

C15:0; pentadecanoic acid; rapamycin; metformin; acarbose; longevity; essential fatty acid

Subject

Biology and Life Sciences, Aging

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