Similar Datasets
Project description:Epigenetic alterations are among the prominent drivers of cellular senescence and/or aging, intricately orchestrating gene expression programs during these processes. Many studies have investigated the histone modification mechanisms that regulate cellular senescence and aging. In this study, we show that histone lactylation, an identified histone modification that integrates metabolic processes, epigenetic regulation of gene expression and cellular activities in response to internal and external cues, plays a pivotal role in counteracting senescence and mitigating dysfunctions of skeletal muscle in aged mice. Mechanistically, histone lactylation levels markedly decrease during cellular senescence but are restored under hypoxic conditions primarily due to elevated glycolytic activity. The enrichment of histone lactylation at promoters is essential for sustaining the expression of genes involved in the cell cycle and DNA repair pathways, thereby inhibiting cellular senescence. Furthermore, the modulation of enzymes crucial for histone lactylation, including p300 and HDAC1, leads to reduced histone lactylation and accelerated cellular senescence. Consistently, the suppression of glycolysis and the depletion of histone lactylation are also observed during skeletal muscle aging. Running exercise increases the levels of glycolysis and histone lactylation, which in turn upregulate key genes in the DNA repair and proteostasis pathways, thereby helping to preserve the proper function of skeletal muscle. Our study highlights the significant roles of histone lactylation in modulating cellular senescence as well as aging-related tissue function, suggesting that this modification may serve as an innovative biomarker for senescence and provides a promising avenue for antiaging intervention via metabolic manipulation.
2024-05-01 | GSE226005 | GEO
Project description:Epigenetic alterations are among the prominent drivers of cellular senescence and/or aging, intricately orchestrating gene expression programs during these processes. Many studies have investigated the histone modification mechanisms that regulate cellular senescence and aging. In this study, we show that histone lactylation, an identified histone modification that integrates metabolic processes, epigenetic regulation of gene expression and cellular activities in response to internal and external cues, plays a pivotal role in counteracting senescence and mitigating dysfunctions of skeletal muscle in aged mice. Mechanistically, histone lactylation levels markedly decrease during cellular senescence but are restored under hypoxic conditions primarily due to elevated glycolytic activity. The enrichment of histone lactylation at promoters is essential for sustaining the expression of genes involved in the cell cycle and DNA repair pathways, thereby inhibiting cellular senescence. Furthermore, the modulation of enzymes crucial for histone lactylation, including p300 and HDAC1, leads to reduced histone lactylation and accelerated cellular senescence. Consistently, the suppression of glycolysis and the depletion of histone lactylation are also observed during skeletal muscle aging. Running exercise increases the levels of glycolysis and histone lactylation, which in turn upregulate key genes in the DNA repair and proteostasis pathways, thereby helping to preserve the proper function of skeletal muscle. Our study highlights the significant roles of histone lactylation in modulating cellular senescence as well as aging-related tissue function, suggesting that this modification may serve as an innovative biomarker for senescence and provides a promising avenue for antiaging intervention via metabolic manipulation.
2024-05-01 | GSE226007 | GEO
Project description:Epigenetic alterations are among the prominent drivers of cellular senescence and/or aging, intricately orchestrating gene expression programs during these processes. Many studies have investigated the histone modification mechanisms that regulate cellular senescence and aging. In this study, we show that histone lactylation, an identified histone modification that integrates metabolic processes, epigenetic regulation of gene expression and cellular activities in response to internal and external cues, plays a pivotal role in counteracting senescence and mitigating dysfunctions of skeletal muscle in aged mice. Mechanistically, histone lactylation levels markedly decrease during cellular senescence but are restored under hypoxic conditions primarily due to elevated glycolytic activity. The enrichment of histone lactylation at promoters is essential for sustaining the expression of genes involved in the cell cycle and DNA repair pathways, thereby inhibiting cellular senescence. Furthermore, the modulation of enzymes crucial for histone lactylation, including p300 and HDAC1, leads to reduced histone lactylation and accelerated cellular senescence. Consistently, the suppression of glycolysis and the depletion of histone lactylation are also observed during skeletal muscle aging. Running exercise increases the levels of glycolysis and histone lactylation, which in turn upregulate key genes in the DNA repair and proteostasis pathways, thereby helping to preserve the proper function of skeletal muscle. Our study highlights the significant roles of histone lactylation in modulating cellular senescence as well as aging-related tissue function, suggesting that this modification may serve as an innovative biomarker for senescence and provides a promising avenue for antiaging intervention via metabolic manipulation.
2024-05-01 | GSE226006 | GEO
Project description:Epigenetic alterations are among the prominent drivers of cellular senescence and/or aging, intricately orchestrating gene expression programs during these processes. Many studies have investigated the histone modification mechanisms that regulate cellular senescence and aging. In this study, we show that histone lactylation, an identified histone modification that integrates metabolic processes, epigenetic regulation of gene expression and cellular activities in response to internal and external cues, plays a pivotal role in counteracting senescence and mitigating dysfunctions of skeletal muscle in aged mice. Mechanistically, histone lactylation levels markedly decrease during cellular senescence but are restored under hypoxic conditions primarily due to elevated glycolytic activity. The enrichment of histone lactylation at promoters is essential for sustaining the expression of genes involved in the cell cycle and DNA repair pathways, thereby inhibiting cellular senescence. Furthermore, the modulation of enzymes crucial for histone lactylation, including p300 and HDAC1, leads to reduced histone lactylation and accelerated cellular senescence. Consistently, the suppression of glycolysis and the depletion of histone lactylation are also observed during skeletal muscle aging. Running exercise increases the levels of glycolysis and histone lactylation, which in turn upregulate key genes in the DNA repair and proteostasis pathways, thereby helping to preserve the proper function of skeletal muscle. Our study highlights the significant roles of histone lactylation in modulating cellular senescence as well as aging-related tissue function, suggesting that this modification may serve as an innovative biomarker for senescence and provides a promising avenue for antiaging intervention via metabolic manipulation.
2024-05-01 | GSE249561 | GEO
Project description:Histone lactylation antagonizes senescence and skeletal muscle aging via facilitating gene expression reprogramming
| PRJNA938234 | ENA
Project description:Histone lactylation antagonizes senescence and skeletal muscle aging via facilitating gene expression reprogramming [RNA-seq]
| PRJNA938241 | ENA
Project description:Histone lactylation antagonizes senescence and skeletal muscle aging via facilitating gene expression reprogramming [snRNA-seq]
| PRJNA938242 | ENA
Project description:Histone lactylation antagonizes senescence and skeletal muscle aging via facilitating gene expression reprogramming [CUT&Tag]
| PRJNA938243 | ENA
Project description:Histone lactylation antagonizes senescence and skeletal muscle aging via facilitating gene expression reprogramming [RNA-Seq II]
| PRJNA1049487 | ENA
Project description:Senescence is a cell fate that contributes to multiple aging-related pathologies. Despite profound age-associated changes in skeletal muscle (SkM), whether its constituent cells are prone to senesce has not been methodically examined. Herein, using single cell and bulk RNA-sequencing and complementary imaging methods on SkM of young and old mice, we demonstrate that a subpopulation of old fibroadipogenic progenitors highly expresses p16 Ink4a together with multiple senescence-related genes and, concomitantly, exhibits DNA damage and chromatin reorganization. Through analysis of isolated myofibers, we also detail a senescence phenotype within a subset of old cells, governed instead by p2 Cip1 . Administration of a senotherapeutic intervention to old mice countered age-related molecular and morphological changes and improved SkM strength. Finally, we found that the senescence phenotype is conserved in SkM from older humans. Collectively, our data provide compelling evidence for cellular senescence as a hallmark and potentially tractable mediator of SkM aging.
| S-EPMC9491365 | biostudies-literature