The role of fatty acids in aging and longevity

Demographic evidence show a gradual increase in human longevity. However, the increasing age of the world population is a leading risk factor for several age-related diseases. For this reason, investigating the factors that contribute to a long and healthy life has become the main focus of scientific research and public health system. Among the environmental factors, a healthy diet is an important modifiable factor for sustaining healthy aging phenotypes. Specifically, fatty acids have been examined as implicated in aging process because they have critical role in maintaining cell and tissue homeostasis and affect inflammatory and oxidative processes. In this thesis, we aimed is to provide new evidence for a better understanding of the role of fatty acids in aging process and age-related phenotypes. In Study I, we described a simple, sensitive, and reliable method for determining blood fatty acid profile. The method was based on transesterification of the fatty acids (direct, acidic transesterification), and subsequently extracting them with n-hexane. The extracted fatty acids were analysed by gas chromatography with flame ionization detection. The method validation showed satisfactory precision and linearity. In Study II, we compared the blood fatty acid profile of a cohort of LLIs (90-111 years old, n=49) from Sicily to adults (18-64 years old, n=69) and older adults (65-89 years old, n=54) from the same area. In addition, genetic variants in key enzymes related to fatty acid biosynthesis and metabolism were genotyped to investigate a potential genetic predisposition in determining the fatty acid profile. The method described in Study I was employed to determine the fatty acid profile, and genotyping was performed using high-resolution melt analysis. The results showed that blood levels of total polyunsaturated fatty acids (PUFAs) and total trans fatty acids decreased with age, while the levels of saturated fatty acids (SFAs) remained unchanged. Interestingly, distinctively higher circulatory levels of monounsaturated fatty acids (MUFAs) in LLIs compared to adults and older adults were observed. In addition, among LLIs the rs174537 in the fatty acid desaturase 1/2 (FADS1/2) gene was associated with linoleic acid (LA, 18:2n-6) and docosatetraenoic acid (DTA, 22:4n-6) levels, and the rs953413 in the elongase of very long fatty acids 2 (ELOVL2) was associated with DTA levels. Further, the rs174579 and rs174626 genotypes in FADS1/2 significantly affected delta-6 desaturase activity. Overall, the results suggested that LLIs have a different fatty acid profile characterized by high MUFA content, which indicates reduced peroxidation while maintaining membrane fluidity. In Study III, the effect of n-3 PUFAs on telomere length was assessed meta-analytically. Four databases (PubMed, Web of Sciences, Scopus, and the Cochrane Library) were searched from inception until November 2021. Of 573 records, a total of 5 clinical trials were included for the quantitative meta-analysis, comprising a total of 337 participants. The results revealed an overall beneficial effect of n-3 PUFAs on telomere length (mean difference = 0.16; 95% CI, 0.02 to 0.30; p = 0.02). Despite a limited number of studies, our analysis suggests that n-3 PUFAs may positively affect telomere length. In study IV, the relationship between MUFA intake and sarcopenia were examined meta-analytically. A literature search was performed in three databases (PubMed, Scopus, and Web of Science) from inception until August 2022. Of 414 records, a total of 12 observational studies were identified. Ten studies were meta-analysed, comprising a total of 3704 participants. The results revealed that MUFA intake is inversely associated with sarcopenia (standardized mean difference = -0.28, 95% CI: -0.46 to -0.11; p <0.01). Overall, the results suggest that lower MUFA intake maybe associated with a higher risk of sarcopenia. In summary, we presented new evidence on the role of fatty acids in aging and age-related phenotypes. This compiled thesis could contribute substantially to the literature on the importance of fatty acids in healthy aging from novel perspectives.