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.

Mental Health and Religiosity in the Sardinian Blue Zone: Life Satisfaction and Optimism for Aging Well

“…In the Sardinian Blue Zone, a high proportion of shepherds preserving their cultural traditions and being more resistant to change live and the highest gender-balanced presence of centenarians in the world has been experimentally validated (Pes et al, 2015 ; Poulain et al, 2004 ). The successful aging of Sardinians living in the Blue Zone is considered multicausal, that is, it seems to be determined by lifestyle (e.g., engagement in outdoor physically and socioculturally oriented leisure activities), a plant-based diet associated with moderate consumption of meat and dairy products, genetic, environmental (e.g., the higher terrain steepness of the territory induces higher physical and cardiovascular activities), physiological metabolic, sociocultural, and psychological factors (e.g., Fastame et al, 2015 ; Manca et al, 2021 ; Nieddu et al, 2020 ; Pes et al, 2013 ). Regarding the psychosocial dimension of the successful aging in Sardinia, a strand of research has documented that perceived mental health (e.g., negative affect, psychological well-being) of community-based and cognitively intact older individuals of the Sardinian Blue Zone is more preserved compared to that of their peers living in rural areas of Northern Italy or in the Sardinian urban area (for a review, see Hitchcott et al, 2018 ).…”

Hedonic and Eudaimonic Well-Being in Late Adulthood: Lessons From Sardinia’s Blue Zone

“…Regarding the Italian Blue Zone, which is the focus of this article, it is limited to the central-eastern mountainous area of Sardinia, where historically the inhabitants are mainly shepherds and where a similar prevalence of female and male centenarians has been found (Pes et al, 2015). A variety of evidence suggests that different factors contribute to the successful aging of the older individuals living in the Sardinian Blue Zone; specifically, genetic, physiological metabolic and environmental factors, dietary habits (i.e., moderate consumption of meat and dairy products and a high intake of plant-based products), lifestyle, and some positive psychological characteristics have been pointed out (e.g., Manca et al, 2021;Nieddu et al, 2020;Pes et al, 2013). In terms of the psychological markers of successful aging, a research trend has highlighted that cognitively healthy (i.e., assessed through the Mini-Mental State Examination and a battery of working memory tasks) community-dwelling older people of the Sardinian Blue Zone reported fewer depressive signs (e.g., , and better psychological well-being (e.g., than peers presenting the same cognitive and socio-demographic characteristics (e.g., global cognitive efficiency, age, gender, education level) and a similar very simple lifestyle, but who were recruited in a rural area of northern Italy.…”

Fatty Acid Metabolism and Derived-Mediators Distinctive of PPAR-α Activation in Obese Subjects Post Bariatric Surgery

“…The total lipids were extracted from the plasma by a chloroform/methanol 2:1, (v/v) solution, and deuterated EC and NAE were added as internal standards for their quantification. Analyses of EC and NAE from chloroform were carried out by an Agilent 1100 HPLC system (Agilent, Palo Alto, CA, USA) equipped with a mass spectrometry Agilent Technologies QQQ triple quadrupole 6420 (LC-MS/MS) with an ESI source, using positive mode (ESI+) for the compounds and their deuterated homologs quantification as described in [25].…”