Lipid metabolism in sickness and in health: Emerging regulators of lipotoxicity

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(18), P. 3708 - 3730

Published: Sept. 1, 2021

Language: Английский

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Lipids as Regulators of Cellular Senescence

Frontiers in Physiology, Journal Year: 2022, Volume and Issue: 13

Published: March 4, 2022

Lipids are key macromolecules that perform a multitude of biological functions ranging from maintaining structural integrity membranes, energy storage, to signaling molecules. Unsurprisingly, variations in lipid composition and its levels can influence the functional physiological state cell milieu. Cellular senescence is permanent cycle arrest hallmark aging process, as well several age-related pathologies. Senescent cells often characterized by alterations morphology, metabolism, chromatin remodeling exhibit complex pro-inflammatory secretome (SASP). Recent studies have shown regulation specific species play critical role senescence. Indeed, some even contribute low-grade inflammation associated with SASP. Many protein regulators been metabolism. However, link between cellular senescence-associated changes yet be elucidated. Here we systematically review current knowledge on metabolism dynamics content during We focus roles major players regulating Finally, explore future prospects research potential targeted senotherapeutics.

Language: Английский

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Lipid droplets and peroxisomes are co-regulated to drive lifespan extension in response to mono-unsaturated fatty acids

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(5), P. 672 - 684

Published: May 1, 2023

Abstract Dietary mono-unsaturated fatty acids (MUFAs) are linked to longevity in several species. But the mechanisms by which MUFAs extend lifespan remain unclear. Here we show that an organelle network involving lipid droplets and peroxisomes is critical for MUFA-induced Caenorhabditis elegans . upregulate number of fat storage tissues. Increased droplet necessary predicts remaining lifespan. Lipidomics datasets reveal also modify ratio membrane lipids ether lipids—a signature associated with decreased oxidation. In agreement this, decrease oxidation middle-aged individuals. Intriguingly, not only but peroxisome number. A targeted screen identifies genes involved co-regulation peroxisomes, reveals induction both organelles optimal longevity. Our study uncovers homeostasis regulation, opening new avenues interventions delay aging.

Language: Английский

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Lysosomal control of senescence and inflammation through cholesterol partitioning

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(3), P. 398 - 413

Published: March 2, 2023

Language: Английский

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Obesity and lipid metabolism in the development of osteoporosis (Review)

International Journal of Molecular Medicine, Journal Year: 2024, Volume and Issue: 54(1)

Published: May 27, 2024

Osteoporosis is a common bone metabolic disease that causes heavy social burden and seriously threatens life. Improving osteogenic capacity necessary to correct mass loss in the treatment of osteoporosis. Osteoblasts are derived from differentiation marrow mesenchymal stem cells, process opposes adipogenic differentiation. The peroxisome proliferator‑activated receptor γ Wnt/β‑catenin signaling pathways mediate mutual regulation osteogenesis adipogenesis. Lipid substances play an important role occurrence development content proportion lipids modulate activity immunocytes, mainly macrophages, secretion inflammatory factors, such as IL‑1, IL‑6 TNF‑α. These effectors increase promote osteoclasts, which leads imbalance stronger resorption. Obesity also decreases antioxidases oxidative stress, thereby inhibiting osteogenesis. present review starts by examining bidirectional BM‑MSCs, describes detail mechanism affect metabolism, discusses regulatory inflammation stress this process. concludes reasonable adjustment lipids, alleviation storms damage induced lipid imbalances, will improve treat

Language: Английский

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Lipids and lipid metabolism in cellular senescence: Emerging targets for age-related diseases

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 97, P. 102294 - 102294

Published: April 5, 2024

Language: Английский

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Emerging role of senescent microglia in brain aging-related neurodegenerative diseases

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Feb. 20, 2024

Abstract Brain aging is a recognized risk factor for neurodegenerative diseases like Alzheimer's disease, Parkinson's and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), but the intricate interplay between brain pathogenesis of these conditions remains inadequately understood. Cellular senescence considered to contribute cellular dysfunction inflammaging. According threshold theory senescent cell accumulation, vulnerability associated with rates generation clearance within brain. Given role microglia in eliminating cells, accumulation may lead acceleration aging, contributing inflammaging increased diseases. In this review, we propose idea that microglia, which notably vulnerable could potentially serve as central catalyst progression The are emerging promising target mitigating

Language: Английский

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Multiscale biochemical mapping of the brain through deep-learning-enhanced high-throughput mass spectrometry

Nature Methods, Journal Year: 2024, Volume and Issue: 21(3), P. 521 - 530

Published: Feb. 16, 2024

Abstract Spatial omics technologies can reveal the molecular intricacy of brain. While mass spectrometry imaging (MSI) provides spatial localization compounds, comprehensive biochemical profiling at a brain-wide scale in three dimensions by MSI with single-cell resolution has not been achieved. We demonstrate complementary and mapping using MEISTER, an integrative experimental computational (MS) framework. Our framework integrates deep-learning-based reconstruction that accelerates high-mass-resolving MS 15-fold, multimodal registration creating three-dimensional (3D) distributions data integration method fitting cell-specific spectra to 3D datasets. imaged detailed lipid profiles tissues millions pixels large populations acquired from rat identified region-specific contents localizations lipids depending on both cell subpopulations anatomical origins cells. workflow establishes blueprint for future development multiscale characterization

Language: Английский

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Single-cell mapping of lipid metabolites using an infrared probe in human-derived model systems

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 8, 2024

Abstract Understanding metabolic heterogeneity is the key to uncovering underlying mechanisms of metabolic-related diseases. Current imaging studies suffer from limitations including low resolution and specificity, model systems utilized often lack human relevance. Here, we present a single-cell platform enable direct lipid metabolism with high specificity in various human-derived 2D 3D culture systems. Through incorporation an azide-tagged infrared probe, selective detection newly synthesized lipids cells tissue became possible, while simultaneous fluorescence enabled cell-type identification complex tissues. In proof-of-concept experiments, were directly visualized human-relevant among different cell types, mutation status, differentiation stages, over time. We identified upregulated progranulin-knockdown induced pluripotent stem their differentiated microglia cells. Furthermore, observed that neurons brain organoids exhibited significantly lower compared astrocytes.

Language: Английский

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A lipidome landscape of aging in mice

Nature Aging, Journal Year: 2024, Volume and Issue: 4(5), P. 709 - 726

Published: April 12, 2024

Language: Английский

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