Abstract
Lipidomic analyses of the frontal cortex of Rhesus macaques across three selected age groups (young, sexually-mature, old) revealed that docosahexaenoic acids (DHAs) displayed notable and unique accretions in sexually-mature macaques for all phospholipid classes examined, which were not observable in all remaining polyunsaturated fatty acids (PUFAs) investigated. On the other hand, arachidonic acid (ARA) exhibited sharp attritions in the membrane lipidomes of sexually-mature macaques, a decline which was attenuated only for cardiolipins (CLs). DHA enrichment in phospholipids was lost in old macaques, with accompanying augmentations in very-long-chain sphingomyelins (VLC-SMs). Age-dependent alterations in membrane lipidomes point to a possibly complex temporal interplay between DHA-enriched membrane microdomains and SM-/cholesterol-rich rafts in neural membranes during normative aging. Lipid co-regulation data revealed an increasingly intense degree of co-regulation between membrane lipid classes with age, and suggest that reduction in CLs during normative brain aging may prompt alternative membrane lipid synthetic pathways driven by a compromised energy availability in the aging brain.
Highlights
The brain invests an estimated 26% of its net ATP expenditure in maintaining phospholipid dynamics, which comprises processes including de novo biosynthesis, remodeling, as well as preserving the asymmetric distributions of specific types of phospholipids in cellular and subcellular membrane bilayers [1]
The half-life of docosahexaenoic acids (DHAs) in the brain is estimated at approximately 2.5 years [46], which is about 20 times longer than that in the rest of the body, implying that specific mechanism(s) probably exist in the brain that prioritizes its DHA requirement over other body regions in order to maintain a persistent level of DHA in neural membranes [14]
An in-depth understanding into how precisely the lipid dynamics of neural membranes may be maintained throughout the course of life could potentially unveil novel, hitherto unknown mechanisms that essentially underlie the process of normative brain aging
Summary
The brain invests an estimated 26% of its net ATP expenditure in maintaining phospholipid dynamics, which comprises processes including de novo biosynthesis, remodeling, as well as preserving the asymmetric distributions of specific types of phospholipids in cellular and subcellular membrane bilayers [1]. Model membrane assays have demonstrated that whereas cholesterol solubility is markedly diminished in phosphatidylcholine (PC) bilayers comprising polyunsaturated fatty acids (PUFAs) at both the sn-1 and sn-2 positions, the presence of a single DHA at the sn-2 position for phosphatidylethanolamine (PE) bilayers is sufficient to elicit similar reduction in cholesterol solubility [4]. A precise distribution of fatty acyl heterogeneity across various phospholipid classes would, be of immense importance in maintaining membrane lipid integrity and proper functioning of the brain
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