Circulating fatty acids and endocannabinoidome-related mediator profiles associated to human longevity

Abstract

To evaluate whether a peculiar plasma profile of fatty acids and endocannabinoidome (eCBome)-related mediators may be associated to longevity, we assessed them in octogenarians (Old; n=42) living in the east-central mountain area of Sardinia, a High-Longevity Zone (HLZ), compared to sexagenarian (Young; n=21) subjects from the same area, and to Olds (n=22) from the Northern Sardinia indicated as Lower-Longevity Zone (LLZ). We found significant increases in conjugated linoleic acid (CLA) and heptadecanoic acid (17:0) levels in Old-HLZ with respect to younger subjects and Old-LLZ subjects. Young-HLZ subjects exhibited higher circulating levels of pentadecanoic acid (15:0) and retinol. Palmitoleic acid (POA) was elevated in both Young and Old subjects from the HLZ. eCBome profile showed a significantly increased plasma level of the two endocannabinoids, N-arachidonoyl-ethanolamine (AEA) and 2-arachidonoyl-glycerol (2-AG) in Old-HLZ subjects compared to Young-HLZ and Old-LLZ respectively. In addition, we found increased N-oleoyl-ethanolamine (OEA), 2-linoleoyl-glycerol (2-LG) and 2-oleoyl-glycerol (2-OG) levels in Old-HLZ group with respect to Young-HLZ (as for OEA an d 2-LG) and both the Old-LLZ and Young-HLZ for 2-OG. The endogenous metabolite of docosahexaenoic acid (DHA), N-docosahexaenoyl-ethanolamine (DHEA) was significantly increased in Old-HLZ subjects. In conclusion, our results suggest that in the HLZ area, Young and Old subjects exhibited a favourable, albeit distinctive, fatty acids and eCBome profile that may be indicative of a metabolic pattern potentially protective from adverse chronic conditions. These factors could point to a suitable physiological metabolic pattern that may counteract the adverse stimuli leading to age-related disorders such as neurodegenerative and metabolic diseases.

Keywords: Conjugated linoleic acid; Endocannabinoidome; Longevity; Metabolism; Odd-chain saturated fatty acids; Palmitoleic acid.

Fig. 1

Mean values ± SEM of POA (a), CLA (b), 15:0 (c) and 17:0 (d), expressed as mol% of total FAs, in 42 octogenarians (> 80 years) from an area of Sardinia that possesses a strikingly high level of long-living people (Old-HLZ); 21 subjects (65–70 years) from the same zone (Young-HLZ) and 22 octogenarians (> 80 years) from a different area of Sardinia with a distinctly lower level of longevity (Old-LLZ). To assess the statistical significance between groups, we performed the Kruskal-Wallis test (one-way ANOVA on ranks) followed by Dunn’s correction for multiple comparisons. Different letters indicate significant differences amongst groups (p≤0.05). (POA, palmitoleic acid; CLA, conjugated linoleic acid)

Fig. 2

Mean values ± SEM of retinol (a), expressed as nmoles/ml plasma, and peroxisomal beta-oxidation index (DHA/EPA) (b) in 42 octogenarians (> 80 years) from an area of Sardinia that possesses a strikingly high level of long-living people (Old-HLZ); 21 subjects (65–70 years) from the same zone (Young-HLZ) and 22 octogenarians (> 80 years) from a different area with a distinctly lower level of longevity (Old-LLZ). To assess the statistical significance between groups, we performed the Kruskal-Wallis test (one-way ANOVA on ranks) followed by Dunn’s correction for multiple comparisons. Different letters indicate significant differences amongst groups (p≤0.05). (EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid)

Fig. 3

Mean values ± SEM expressed as nmoles/ml plasma of endocannabinoidome mediators. N-acyl-ethanolamines (a) and 2-monoacyl-glycerol (b) in 42 octogenarians (> 80 years) from an area of Sardinia that possesses a strikingly high level of long-living people (Old-HLZ); 21 subjects (65–70 years) from the same zone (Young-HLZ) and 22 octogenarians (> 80 years) from a different area with a distinctly lower level of longevity (Old-LLZ). To assess the statistical significance between groups, we performed the Kruskal-Wallis test (one-way ANOVA on ranks) followed by Dunn’s correction for multiple comparisons. Different letters indicate significant differences amongst groups (p≤0.05). Anandamide (AEA), palmitoyl-ethanolamide (PEA), oleoyl-ethanolamide (OEA), docosahexaenoyl-ethanolamide (DHAEA), 2-arachidonoyl-glycerol (2-AG), 2-palmitoyl-glycerol (2-PG), 2-linoleoyl-glycerol (2-LG), 2-oleoyl-glycerol (2-OG)