Selective brain regional changes in lipid profile with human aging

Mota‐Martorell, Natàlia; Andrés‐Benito, Pol; Martín-Gari, Meritxell; Galo-Licona, José Daniel; Sol, Joaquím; Fernández-Bernal, Anna; Portero‐Otín, Manuel; Ferrer, Isidro; Jové, Mariona; Pamplona, Reinald

doi:10.1007/s11357-022-00527-1

Cited by 18 publications

(22 citation statements)

References 40 publications

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“…Furthermore, the polyunsaturated nature of these fatty acids makes them more prone to oxidative damage (Mota-Martorell et al, 2022), so the increased levels of both AA and DPA observed with age suggest a favored environment to inflammation and oxidative stress in tissues with age, as previously described (de Almeida et al, 2020).…”

Section: Ta B L E 1 Clusters Of Inter-related Metabolitesmentioning

confidence: 64%

Plasma acylcarnitines and gut‐derived aromatic amino acids as sex‐specific hub metabolites of the human aging metabolome

et al. 2023

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Aging biology entails a cell/tissue deregulated metabolism that affects all levels of biological organization. Therefore, the application of “omic” techniques that are closer to phenotype, such as metabolomics, to the study of the aging process should be a turning point in the definition of cellular processes involved. The main objective of the present study was to describe the changes in plasma metabolome associated with biological aging and the role of sex in the metabolic regulation during aging. A high‐throughput untargeted metabolomic analysis was applied in plasma samples to detect hub metabolites and biomarkers of aging incorporating a sex/gender perspective. A cohort of 1030 healthy human adults (45.9% females, and 54.1% males) from 50 to 98 years of age was used. Results were validated using two independent cohorts (1: n = 146, 53% females, 30–100 years old; 2: n = 68, 70% females, 19–107 years old). Metabolites related to lipid and aromatic amino acid (AAA) metabolisms arose as the main metabolic pathways affected by age, with a high influence of sex. Globally, we describe changes in bioenergetic pathways that point to a decrease in mitochondrial β‐oxidation and an accumulation of unsaturated fatty acids and acylcarnitines that could be responsible for the increment of oxidative damage and inflammation characteristic of this physiological process. Furthermore, we describe for the first time the importance of gut‐derived AAA catabolites in the aging process describing novel biomarkers that could contribute to better understand this physiological process but also age‐related diseases.

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Section: Ta B L E 1 Clusters Of Inter-related Metabolitesmentioning

confidence: 64%

Plasma acylcarnitines and gut‐derived aromatic amino acids as sex‐specific hub metabolites of the human aging metabolome

et al. 2023

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“…Fatty acyl groups were analyzed as methyl esters derivatives by gas chromatography as previously described (Mota-Martorell et al, 2022). For tissue homogenization, 50mg of cerebral cortex and WM was processed in a buffer containing 180mM KCl, 5mM MOPS, 2mM EDTA, 1mM diethylenetriaminepentaacetic acid, and 1μM butylated hydroxytoluene.…”

Section: Methodsmentioning

confidence: 99%

“…The density of double-bonds in the membrane was calculated with the Double-Bond Index, DBI = [(1 × Σmol% monoenoic) + (2 × Σmol% dienoic) + (3 × Σmol% trienoic) + (4 × Σmol% tetraenoic) + (5 × Σmol% pentaenoic) + (6 × Σmol% hexaenoic)]. Membrane susceptibility to peroxidation was calculated with the Peroxidizability Index, PI (a) = [(0.025 × Σmol% monoenoic) + (1 × Σmol% dienoic) + (2 × Σmol% trienoic) + (4 × Σmol% tetraenoic) + (6 × Σmol% pentaenoic) + (8 × Σmol% hexaenoic)] (Mota-Martorell et al, 2022), and PI (b) = [(0.015 × Σmol% monoenoic) + (1 × Σmol% dienoic) + (2 × Σmol% trienoic) + (3 × Σmol% tetraenoic) + (4 × Σmol% pentaenoic) + (5 × Σmol% hexaenoic)] (Yin et al, 2011).…”

Section: Methodsmentioning

confidence: 99%

“…Thus, total lipid content ―including fatty acids, GPs (especially ether lipids), SLs, and cholesterol― decreases after age 50 (Naudi et al, 2015). Lipoxidation-derived protein damage also increases with age in a region-specific manner (Horrocks et al, 1981; Soderberg et al, 1990; Svennerholm et al, 1991; Svennerholm et al, 1994; McNamara et al, 2008; Ledesma et al, 2012; Hancock et al, 2015; Norris et al, 2015; Dominguez et al, 2016; Cabre et al, 2017; Hancock et al, 2017; Cabre et al, 2018; Diaz et al, 2018; Dominguez-Gonzalez et al, 2018; Jove et al, 2019; Pamplona et al, 2019; Jove et al, 2021; Mota-Martorell et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

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Lipidomic alterations in the cerebral cortex and white matter in sporadic Alzheimer’s disease

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Andrés‐Benito

et al. 2022

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Aims: Non-targeted lipidomics analysis was conducted in post-mortem human frontal cortex area 8 (GM) and white matter of the frontal lobe centrum semi-ovale (WM) to identify lipidomes in middle-aged individuals with no neurofibrillary tangles and senile plaques, and cases at progressive stages of sporadic Alzheimer's disease (sAD). Methods: Lipidomic analysis using an LC-MS/MS platform was carried out in selected cases with suitable post-mortem lacking co-morbidities and concomitant brain pathologies. Complementary data were obtained using RT-qPCR and immunohistochemistry. Results: The WM shows an adaptive lipid phenotype resistant to lipid peroxidation, characterized by a lower fatty acid unsaturation, peroxidizability index, and higher ether lipid content than the GM. Changes in the lipidomic profile more marked in the WM than in GM occur in AD with disease progression. WM alterations are characterized by a decline in the content of branched fatty acid esters of hydroxy fatty acids (FAHFA), diacylglycerols (DG), triacylglycerols (TG), glycerophospholipids (GP) (especially ether lipids), and sphingolipids (especially sulfatides, ceramides, and glycosphingolipids). The GM acquires a fatty acid profile prone to peroxidation in sAD, while WM reinforces its peroxidation-resistant trait. Transcriptomic data point to additional defects of peroxisomal function. Conclusions: Four functional categories are associated with the different lipid classes affected in sAD: membrane structural composition, bioenergetics, antioxidant protection, and bioactive lipids, with deleterious consequences affecting both neurons and glial cells favoring disease progression.

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“…The brain tissue exhibits the most complex lipidome in the whole body (Mota-Martorell et al, 2022;Naudí et al, 2015;Yoon et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Molecular and biophysical features of hippocampal “lipid rafts aging” are modified by dietary n‐3 long‐chain polyunsaturated fatty acids

et al. 2023

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Abstract“Lipid raft aging” in nerve cells represents an early event in the development of aging‐related neurodegenerative diseases, such as Alzheimer's disease. Lipid rafts are key elements in synaptic plasticity, and their modification with aging alters interactions and distribution of signaling molecules, such as glutamate receptors and ion channels involved in memory formation, eventually leading to cognitive decline. In the present study, we have analyzed, in vivo, the effects of dietary supplementation of n‐3 LCPUFA on the lipid structure, membrane microviscosity, domain organization, and partitioning of ionotropic and metabotropic glutamate receptors in hippocampal lipid raffs in female mice. The results revealed several lipid signatures of “lipid rafts aging” in old mice fed control diets, consisting in depletion of n‐3 LCPUFA, membrane unsaturation, along with increased levels of saturates, plasmalogens, and sterol esters, as well as altered lipid relevant indexes. These changes were paralleled by increased microviscosity and changes in the raft/non‐raft (R/NR) distribution of AMPA‐R and mGluR5. Administration of the n‐3 LCPUFA diet caused the partial reversion of fatty acid alterations found in aged mice and returned membrane microviscosity to values found in young animals. Paralleling these findings, lipid rafts accumulated mGluR5, NMDA‐R, and ASIC2, and increased their R/NR proportions, which collectively indicate changes in synaptic plasticity. Unexpectedly, this diet also modified the lipidome and dimension of lipid rafts, as well as the domain redistribution of glutamate receptors and acid‐sensing ion channels involved in hippocampal synaptic plasticity, likely modulating functionality of lipid rafts in memory formation and reluctance to age‐associated cognitive decline.

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Selective brain regional changes in lipid profile with human aging

Cited by 18 publications

References 40 publications

Plasma acylcarnitines and gut‐derived aromatic amino acids as sex‐specific hub metabolites of the human aging metabolome

Plasma acylcarnitines and gut‐derived aromatic amino acids as sex‐specific hub metabolites of the human aging metabolome

Lipidomic alterations in the cerebral cortex and white matter in sporadic Alzheimer’s disease

Molecular and biophysical features of hippocampal “lipid rafts aging” are modified by dietary n‐3 long‐chain polyunsaturated fatty acids

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