Metabolic View on Human Healthspan: A Lipidome-Wide Association Study

Abstract

As ageing is a major risk factor for the development of non-communicable diseases, extending healthspan has become a medical and societal necessity. Precise lipid phenotyping that captures metabolic individuality could support healthspan extension strategies. This study applied ‘omic-scale lipid profiling to characterise sex-specific age-related differences in the serum lipidome composition of healthy humans. A subset of the COmPLETE-Health study, composed of 73 young (25.2 ± 2.6 years, 43% female) and 77 aged (73.5 ± 2.3 years, 48% female) clinically healthy individuals, was investigated, using an untargeted liquid chromatography high-resolution mass spectrometry approach. Compared to their younger counterparts, aged females and males exhibited significant higher levels in 138 and 107 lipid species representing 15 and 13 distinct subclasses, respectively. Percentage of difference ranged from 5.8% to 61.7% (females) and from 5.3% to 46.0% (males), with sphingolipid and glycerophophospholipid species displaying the greatest amplitudes. Remarkably, specific sphingolipid and glycerophospholipid species, previously described as cardiometabolically favourable, were found elevated in aged individuals. Furthermore, specific ether-glycerophospholipid and lyso-glycerophosphocholine species displayed higher levels in aged females only, revealing a more favourable lipidome evolution in females. Altogether, age determined the circulating lipidome composition, while lipid species analysis revealed additional findings that were not observed at the subclass level.

Fundamental Clock of Biological Aging: Convergence of Molecular, Neurodegenerative, Cognitive and Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology

“…To better understand advanced biological aging, it is necessary to examine the interrelation of molecular determinants of the biological clock with the somatic and mental health conditions [ 193 , 194 , 195 ]. Cross-talk of biological, cognitive, and psychological clocks provides an integrative contribution to healthy and advanced aging [ 162 , 194 , 195 ].…”

“…To better understand advanced biological aging, it is necessary to examine the interrelation of molecular determinants of the biological clock with the somatic and mental health conditions [ 193 , 194 , 195 ]. Cross-talk of biological, cognitive, and psychological clocks provides an integrative contribution to healthy and advanced aging [ 162 , 194 , 195 ]. However, the fundamental (i.e., essential for all levels of biological organization) role of spontaneous PTMs in organism aging and dysfunctions is currently not targeted by systematic proteome-wide exploration.…”

Activation Mechanisms of the VPS34 Complexes

“…In actual human bodies, lipid compositions differ between sexes and between aged and young populations [237]. For example, alkyl (ether) and saturated forms of phospholipids are increased in older populations compared with younger populations [237].…”

“…In actual human bodies, lipid compositions differ between sexes and between aged and young populations [237]. For example, alkyl (ether) and saturated forms of phospholipids are increased in older populations compared with younger populations [237]. Also, changes in lipid compositions have been found in various diseases, including a rare neurometabolic syndrome (Sjögren-Larsson syndrome (SLS)) [238] and various types of cancer [239].…”

How Ceramides Orchestrate Cardiometabolic Health—An Ode to Physically Active Living

“…The next step forward is the establishment of biological reference intervals for the species, which are amenable to be used in clinical practice. Establishing these reference values through large-scale population studies, while taking variables such as age, sex, physical activity, diet, medication, and circadian rhythm into consideration, is required to distinguish physiological from pathological variations [64,65].…”