Histone β‐hydroxybutyrylation is critical in reversal of sarcopenia

Aging Cell, Journal Year: 2024, Volume and Issue: 23(11)

Published: July 30, 2024

Abstract Sarcopenia, a leading cause for global disability and mortality, is an age‐related muscular disorder, characterized by accelerated muscle mass loss functional decline. It known that caloric restriction (CR), ketogenic diet or endurance exercise lessen sarcopenia elevate circulating β‐hydroxybutyrate (β‐HB) levels. Whether the elevated β‐HB essential to reversal of sarcopenia, however, remains unclear. Here we show in both Caenorhabditis elegans mouse models increase reverse myofiber atrophy improves motor functions at advanced ages. β‐HB‐induced histone lysine β‐hydroxybutyrylation (Kbhb) indispensable sarcopenia. Histone Kbhb enhances transcription genes associated with mitochondrial pathways, including oxidative phosphorylation, ATP metabolic process aerobic respiration. This ultimately leads improve integrity enhance The are validated model CR. Thus, demonstrate induces Kbhb, increases function, reverses

Language: Английский

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A nutrigeroscience approach: Dietary macronutrients and cellular senescence

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(9), P. 1914 - 1944

Published: Aug. 23, 2024

Language: Английский

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Cell Cycle and Senescence Regulation by Podocyte Histone Deacetylase 1 and 2

Journal of the American Society of Nephrology, Journal Year: 2022, Volume and Issue: unknown

Published: Nov. 22, 2022

Background Intact expression of podocyte histone deacetylases (HDAC) during development is essential for maintaining a normal glomerular filtration barrier because its role in modulating DNA damage and preventing premature senescence. Methods Germline podocyte-specific Hdac1 2 ( / ) double-knockout mice were generated to examine the importance these enzymes development. Results Podocyte-specific loss resulted severe proteinuria, kidney failure, collapsing glomerulopathy. -deprived podocytes exhibited classic characteristics senescence, such as senescence-associated β-galactosidase activity lipofuscin aggregates. In addition, damage, likely caused by epigenetic alterations open chromatin conformation, not only cell-cycle entry shown vivo Ki67 FUCCI-2aR mice, but also p21-mediated arrest. Through senescence secretory associated phenotype, damaged secreted proinflammatory cytokines, growth factors, matrix metalloproteinases, resulting subsequent detachment loss, evidenced senescent urine. Conclusions plays an Loss genes double knockout leads sustained loss.

Language: Английский

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Cdc42GAP deficiency contributes to the Alzheimer’s disease phenotype

Brain, Journal Year: 2023, Volume and Issue: 146(10), P. 4350 - 4365

Published: May 31, 2023

Alzheimer's disease, the most common cause of dementia, is a chronic degenerative disease with typical pathological features extracellular senile plaques and intracellular neurofibrillary tangles significant decrease in density neuronal dendritic spines. Cdc42 member small G protein family that plays an important role regulating synaptic plasticity regulated by Cdc42GAP, which switches from active GTP-bound to inactive GDP-bound states downstream pathways via effector proteins. However, few studies have focused on progression disease. In heterozygous Cdc42GAP mouse model exhibited elevated Cdc42-GTPase activity accompanied increased Cdc42-PAK1-cofilin signalling, we found impairments cognitive behaviours, neuron senescence, loss depolymerization F-actin phenotypes including phosphorylated tau (p-T231, AT8), along soluble insoluble Aβ1-42 Aβ1-40, are consistent mice. Interestingly, these significantly age. Furthermore, results quantitative phosphoproteomic analysis hippocampus 11-month-old GAP mice suggested deficiency induces accelerates disease-like through activation GSK-3β dephosphorylation at Ser9, Ser389 and/or phosphorylation Tyr216. addition, overexpression dominant-negative primary hippocampal cortical neurons reversed hyperphosphorylation. Importantly, signalling pathway, Aβ1-42, Aβ1-40 were sections patients compared those healthy controls. Together, data indicated involved such as deficits, spine loss, AT8) possibly GSK-3β, Thus, provide first evidence phenotypes, may new targets for treatment.

Language: Английский

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Roles of extracellular vesicles in ageing-related chronic kidney disease: Demon or angel

Pharmacological Research, Journal Year: 2023, Volume and Issue: 193, P. 106795 - 106795

Published: May 19, 2023

Ageing is a universal and unavoidable phenomenon that significantly increases the risk of developing chronic kidney disease (CKD). It has been reported ageing associated with functional disruption structural damage to kidneys. Extracellular vesicles (EVs), which are nanoscale membranous containing lipids, proteins, nucleic acids, secreted by cells into extracellular spaces. They have diverse functions such as repairing regenerating different forms ageing-related CKD playing crucial role in intercellular communication. This paper reviews etiology CKD, particular attention paid roles EVs carriers signals anti-ageing therapeutic strategies CKD. In this regard, double-edged examined, along potential for their application clinical settings.

Language: Английский

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