New insights into human prefrontal cortex aging with a lipidomics approach

Jové, Mariona; Mota‐Martorell, Natàlia; Torres, Pascual; Portero‐Otín, Manuel; Ferrer, Isidró; Pamplona, Reinald

doi:10.1080/14789450.2021.1940142

Cited by 12 publications

(6 citation statements)

References 119 publications

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“…Minor but significant changes were detected for the fatty acid profiles with aging, with more substantial changes observed in the cerebellum (increased MUFA and decreased PUFA contents) in contrast to the frontal cortex, which showed a more sustained composition throughout the adult lifespan of rats. These observations are in line with previous studies in rats [15], as well as humans [37][38][39][40], suggesting that the maintenance of a fatty acid profile throughout the adult lifespan is a key prerequisite to ensuring optimal neuronal integrity and, surely, brain structure and function. In this line, the steady-state levels of different protein damage markers are also sustained during adult life.…”

Section: Discussionsupporting

confidence: 92%

Age-Related Changes in Lipidome of Rat Frontal Cortex and Cerebellum Are Partially Reversed by Methionine Restriction Applied in Old Age

Jové

Cabré

Mota‐Martorell

et al. 2021

IJMS

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Lipids are closely associated with brain structure and function. However, the potential changes in the lipidome induced by aging remain to be elucidated. In this study, we used chromatographic techniques and a mass spectrometry-based approach to evaluate age-associated changes in the lipidome of the frontal cortex and cerebellum obtained from adult male Wistar rats (8 months), aged male Wistar rats (26 months), and aged male Wistar rats submitted to a methionine restriction diet (MetR)—as an anti-aging intervention—for 8 weeks. The outcomes revealed that only small changes (about 10%) were observed in the lipidome profile in the cerebellum and frontal cortex during aging, and these changes differed, in some cases, between regions. Furthermore, a MetR diet partially reversed the effects of the aging process. Remarkably, the most affected lipid classes were ether-triacylglycerols, diacylglycerols, phosphatidylethanolamine N-methylated, plasmalogens, ceramides, and cholesterol esters. When the fatty acid profile was analyzed, we observed that the frontal cortex is highly preserved during aging and maintained under MetR, whereas in the cerebellum minor changes (increased monounsaturated and decreased polyunsaturated contents) were observed and not reversed by MetR. We conclude that the rat cerebellum and frontal cortex have efficient mechanisms to preserve the lipid profile of their cell membranes throughout their adult lifespan in order to maintain brain structure and function. A part of the small changes that take place during aging can be reversed with a MetR diet applied in old age.

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Section: Discussionsupporting

confidence: 92%

Age-Related Changes in Lipidome of Rat Frontal Cortex and Cerebellum Are Partially Reversed by Methionine Restriction Applied in Old Age

Jové

Cabré

Mota‐Martorell

et al. 2021

IJMS

Self Cite

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“…In fact, the aging mammalian brain membranes in general are subjected to moderate changes, which nonetheless can have extensive impact on cognitive health. Essentially, the proportions of polyunsaturated fatty acids (PUFAs), short-chained sphingolipids, cholesterol and phospholipids decrease in aging mouse and human brains and human cerebrospinal fluid, while the concentration of long-chained sphingolipids and monounsaturated fatty acids (MUFAs) tend to increase ( Tu et al, 2017 ; Pamplona et al, 2019 ; Hwangbo et al, 2021 ; Jové et al, 2021 ). These cerebral lipidome alterations presumably contribute to age-related neuronal deterioration by causing mitochondrial dysfunction, increasing oxidative stress and altering properties of neuronal membranes.…”

Section: Lipids Alterations During Agingmentioning

confidence: 99%

“…In the case of cholesterol, remodeling in homeostasis pathways and synthesis are responsible for the depletion that is observed in cell membranes of some brain regions. The downregulation of the transporter ApoE and synthesis and the upregulation of the cholesterol-removing enzyme CYP46 in aged humans contributed to lower local cholesterol concentration in the brain ( Martin et al, 2010 ; Jové et al, 2021 ). PUFAs originate either from synthesis in the liver or from diet, and in both cases must pass the blood-brain barrier (BBB) to be incorporated in cerebral cell membranes.…”

Section: Lipids Alterations During Agingmentioning

confidence: 99%

Recent Advances in Studying Age-Associated Lipids Alterations and Dietary Interventions in Mammals

Gille¹,

Galuska²,

Fuchs³

et al. 2021

Front. Aging

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Lipids are involved in a broad spectrum of canonical biological functions, from energy supply and storage by triacylglycerols to membrane formation by sphingolipids, phospholipids and glycolipids. Because of this wide range of functions, there is an overlap between age-associated processes and lipid pathways. Lipidome analysis revealed age-related changes in the lipid composition of various tissues in mice and humans, which were also influenced by diet and gender. Some changes in the lipid profile can be linked to the onset of age-related neurodegenerative diseases like Alzheimer’s disease. Furthermore, the excessive accumulation of lipid storage organelles, lipid droplets, has significant implications for the development of inflammaging and non-communicable age-related diseases. Dietary interventions such as caloric restriction, time-restrictive eating, and lipid supplementation have been shown to improve pertinent health metrics or even extend life span and thus modulate aging processes.

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“…The remaining three D1 communities are related to neuronal activity. These include mechanisms involved in cognitive dynamics, such as the D1_C1 community associated with the neuronal lipidome and key pathways for cognitive functioning [82,83], as well as the D1_C2 community linked to the regulation of neuronal cell lifespan through potentially cell trimming [84]. D1_C4 is involved in axonogenesis, which, together with the former communities, potentially regulates brain plasticity [85,86].…”

Section: Gene-wise Analysismentioning

confidence: 99%

A Transcriptome Community-and-Module Approach of the Human Mesoconnectome

Paredes

López

Covantes-Osuna

et al. 2021

Entropy

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Graph analysis allows exploring transcriptome compartments such as communities and modules for brain mesostructures. In this work, we proposed a bottom-up model of a gene regulatory network to brain-wise connectome workflow. We estimated the gene communities across all brain regions from the Allen Brain Atlas transcriptome database. We selected the communities method to yield the highest number of functional mesostructures in the network hierarchy organization, which allowed us to identify specific brain cell functions (e.g., neuroplasticity, axonogenesis and dendritogenesis communities). With these communities, we built brain-wise region modules that represent the connectome. Our findings match with previously described anatomical and functional brain circuits, such the default mode network and the default visual network, supporting the notion that the brain dynamics that carry out low- and higher-order functions originate from the modular composition of a GRN complex network

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New insights into human prefrontal cortex aging with a lipidomics approach

Cited by 12 publications

References 119 publications

Age-Related Changes in Lipidome of Rat Frontal Cortex and Cerebellum Are Partially Reversed by Methionine Restriction Applied in Old Age

Age-Related Changes in Lipidome of Rat Frontal Cortex and Cerebellum Are Partially Reversed by Methionine Restriction Applied in Old Age

Recent Advances in Studying Age-Associated Lipids Alterations and Dietary Interventions in Mammals

A Transcriptome Community-and-Module Approach of the Human Mesoconnectome

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