Cooper, B. R. | bioRxiv Science

bioRxiv2024

Multiplatform lipid analysis of the brain of aging mice by mass spectrometry

Lipids are an integral part of brain structure and function and represent about 50% of the dry weight of the brain. Despite their importance, the complexity and variations in the abundance of brain lipids due to aging remain poorly understood. For maximum coverage and multi-platform validation, we applied three complementary mass spectrometry-based analytical approaches: multiple reaction monitoring (MRM) profiling, untargeted liquid chromatography tandem mass spectrometry (LC-MS/MS), and desorption electrospray ionization-MS imaging (DESI-MSI). We used three different age groups of mice, namely adult (3-4 months), middle-aged (10 months) and old (19-21 months). Phospholipids including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) showed higher abundance, while phosphatidylinositols (PI) and phosphatidylserines (PS) generally showed lower abundance in the brains of old mice compared to adults or middle-aged mice. Polyunsaturated fatty acids, such as docosahexaenoic acid (DHA) and arachidonic acid (AA), as well as hexosylceramides (HexCer), sulfated hexosylceramides (SHexCer) and sphingomyelins (SM) were among the most abundant lipid species in the brains of old mice. DESI-MSI showed variations in the spatial distribution of many of the lipids confirmed by MRM and LC-MS/MS profiling. Interrogation of lipidomic data with recent proteomics data obtained from the same tissues revealed changes in the abundance and phosphorylation levels of several proteins potentially linked to ceramide (Cer), hexosylceramide (HexCer), fatty acids (FA), phosphatidylinositol (PI), sphingomyelin (SM) and sulfatides (SHexCer) metabolism and correlated well with the multiplatform lipid surveillance. Our findings offer insight into age-dependent changes in brain lipid profiles and their potential contribution to age-related cognitive decline.

neuroscience↗

bioRxiv2021

Quantitative proteomic and metabolomic profiling reveals altered mitochondrial metabolism and folate biosynthesis pathways in the aging Drosophila eye

Aging is associated with increased risk of ocular disease, suggesting that age-associated molecular changes in the eye increase its vulnerability to damage. Although there are common pathways involved in aging at an organismal level, different tissues and cell types exhibit specific changes in gene expression with advanced age. Drosophila melanogaster is an established model system for studying aging and neurodegenerative disease, that also provides a valuable model for studying age-associated ocular disease. Flies, like humans, exhibit decreased visual function and increased risk of retinal degeneration with age. Here, we profiled the aging proteome and metabolome of the Drosophila eye, and compared these data with age-associated transcriptomic changes from both eyes and photoreceptors to identify alterations in pathways that could lead to age-related phenotypes in the eye. Notably, the proteomic and metabolomic changes observed in the aging eye are distinct from those observed in the head or whole fly, suggesting that tissue-specific changes in protein abundance and metabolism occur in the aging fly. Our integration of the proteomic, metabolomic and transcriptomic data reveals that changes in metabolism, potentially due to decreases in availability of B vitamins, together with chronic activation of the immune response, may underpin many of the events observed in the aging Drosophila eye. We propose that targeting these pathways in the genetically tractable Drosophila system may help to identify potential neuroprotective approaches for neurodegenerative and age-related ocular diseases.

biochemistry↗