Lipidomics of familial longevity

Abstract

Middle-aged offspring of nonagenarians, as compared to their spouses (controls), show a favorable lipid metabolism marked by larger LDL particle size in men and lower total triglyceride levels in women. To investigate which specific lipids associate with familial longevity, we explore the plasma lipidome by measuring 128 lipid species using liquid chromatography coupled to mass spectrometry in 1526 offspring of nonagenarians (59 years ± 6.6) and 675 (59 years ± 7.4) controls from the Leiden Longevity Study. In men, no significant differences were observed between offspring and controls. In women, however, 19 lipid species associated with familial longevity. Female offspring showed higher levels of ether phosphocholine (PC) and sphingomyelin (SM) species (3.5–8.7%) and lower levels of phosphoethanolamine PE (38:6) and long-chain triglycerides (TG) (9.4–12.4%). The association with familial longevity of two ether PC and four SM species was independent of total triglyceride levels. In addition, the longevity-associated lipid profile was characterized by a higher ratio of monounsaturated (MUFA) over polyunsaturated (PUFA) lipid species, suggesting that female offspring have a plasma lipidome less prone to oxidative stress. Ether PC and SM species were identified as novel longevity markers in females, independent of total triglycerides levels. Several longevity-associated lipids correlated with a lower risk of hypertension and diabetes in the Leiden Longevity Study cohort. This sex-specific lipid signature marks familial longevity and may suggest a plasma lipidome with a better antioxidant capacity, lower lipid peroxidation and inflammatory precursors, and an efficient beta-oxidation function.

Demographic and clinical variables affecting mid‐ to late‐life trajectories of plasma ceramide and dihydroceramide species

“…Thus, the homeostasis of ceramide metabolism may be critical in regulating lifespan and age‐associated diseases (Cutler & Mattson, 2001; Rao et al ., 2007). Indeed, it has been increasingly recognized, from the cellular to human level, that perturbations in ceramide metabolism are associated with longevity (Yu et al ., 2012; Gonzalez‐Covarrubias et al ., 2013; Cutler et al ., 2014; Huang et al ., 2014) and the development and progression of many age‐related diseases including cancer (Alberg et al ., 2013), atherosclerosis (Ichi et al ., 2006), insulin resistance and diabetes (Holland et al ., 2007; Holland & Summers, 2008; Boon et al ., 2013), Alzheimer's disease (Mielke et al ., 2012), and Parkinson's disease (Mielke et al ., 2013). …”

Lipidomics

“…48,55,61 In a family cohort study exploring the relation of circulating lipids to longevity, a sex-specific lipid signature was associated with familial longevity in women, whereas no significant differences were observed in men. 33 Female middle-aged offsprings of nonagenarians (between 90 and 100 years old) showed a higher ratio of monounsaturated instead of polyunsaturated lipid species and thus the authors suggest that the female plasma lipidome is less prone for oxidative stress. Furthermore, they identified ether phosphatidylcholine and sphingomyelin species as novel longevity biomarkers in women, independent of total TG levels.…”

“…Thus, we include articles not only with lipidomics but also with measurements related to lipids and CVDs. [33][34][35][36][37][38][39][40] A summary of the studies is presented in Table 3. Lipid profiling has shown promising results in diabetes mellitus, [41][42][43][44][45][46][47] CVDs, 35,37,38,48-52 metabolic disorders, 40,53,54 dietary habits, and obesity, 47,49,[55][56][57][58][59][60][61] as well as in determining response to drug therapy.…”

Nuclear hormone receptors as mediators of metabolic adaptability following reproductive perturbations

“…Diets rich in MUFAs and PUFAs have a beneficial impact on mammalian torpor, whereas diets rich in SFAs have a negative effect. 58,59 Alternatively, SFAs are critical for reproductive health. They make up >70% of human oocytes, of which SA and PA are the most abundant, whereas, MUFAs make up <15%.…”