Comprehensive transcriptome analysis reveals altered mRNA splicing and post-transcriptional changes in the aged mouse brain DOI Creative Commons
Nisha Hemandhar-Kumar, Verena Kluever, Emanuel Barth

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(6), P. 2865 - 2885

Published: March 12, 2024

Abstract A comprehensive understanding of molecular changes during brain aging is essential to mitigate cognitive decline and delay neurodegenerative diseases. The interpretation mRNA alterations influenced by the health age animal cohorts studied. Here, we carefully consider these factors provide an in-depth investigation splicing dynamics in mouse brain, combining short- long-read sequencing technologies with extensive bioinformatic analyses. Our findings encompass a spectrum age-related changes, including differences isoform usage, decreased module showing increased expression neuronal genes. Notably, our results indicate reduced abundance isoforms leading nonsense-mediated RNA decay suggest regulatory role for RNA-binding proteins, indicating that their regulation may be altered reshaping aged transcriptome. Collectively, study highlights importance studying events aging.

Language: Английский

Chronic inflammation and the hallmarks of aging DOI Creative Commons
Jordan J. Baechle, Nan Chen, Priya Makhijani

et al.

Molecular Metabolism, Journal Year: 2023, Volume and Issue: 74, P. 101755 - 101755

Published: June 16, 2023

Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, low-grade inflammation during aging, without overt infection, is defined as "inflammaging," which associated with increased morbidity mortality in population. Emerging evidence suggests a bidirectional cyclical relationship between development age-related conditions, such cardiovascular diseases, neurodegeneration, cancer, frailty. How crosstalk other underlies biological mechanisms disease thus particular interest current geroscience research.

Language: Английский

Citations

166
Targeting dysregulated lipid metabolism for the treatment of Alzheimer's disease and Parkinson's disease: Current advancements and future prospects DOI Creative Commons
Bin Tong,

Yaoqi Ba,

Zhengyang Li

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 196, P. 106505 - 106505

Published: April 19, 2024

Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features AD memory decline cognitive dysfunction, while PD mainly manifests as motor dysfunction such limb tremors, muscle rigidity abnormalities, slow gait. Abnormalities in cholesterol, sphingolipid, glycerophospholipid metabolism have been demonstrated to directly exacerbate progression by stimulating Aβ deposition tau protein tangles. Indirectly, abnormal lipids can increase burden on brain vasculature, induce insulin resistance, affect structure neuronal cell membranes. Abnormal lipid leads through inducing accumulation α-syn, mitochondria endoplasmic reticulum, ferroptosis. Great progress has made targeting abnormalities for treatment recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, monoclonal antibodies apolipoprotein E (ApoE). This review comprehensively summarizes involvement dysregulated pathogenesis PD, application Lipid Monitoring, emerging regulatory drug targets. A better understanding lipidological bases may pave way developing effective prevention methods neurodegenerative disorders.

Language: Английский

Citations

22
Energy metabolism in health and diseases DOI Creative Commons
Hui Liu, Shuo Wang, Jianhua Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 18, 2025

Language: Английский

Citations

15
Ovarian aging: energy metabolism of oocytes DOI Creative Commons
Shenglan Bao, Tailang Yin,

Su Liu

et al.

Journal of Ovarian Research, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 31, 2024

Abstract In women who are getting older, the quantity and quality of their follicles or oocytes decline. This is characterized by decreased ovarian reserve function (DOR), fewer remaining oocytes, lower oocytes. As more choose to delay childbirth, decline in fertility associated with age has become a significant concern for modern women. The oocyte key indicator aging. Many studies suggest that age-related changes energy metabolism may impact quality. Changes affect adenosine 5'-triphosphate (ATP) production, but how related products proteins influence remains largely unknown. review focuses on aging its potential quality, as well therapeutic strategies partially metabolism. research aims enhance our understanding metabolism, identification biomarkers treatment methods.

Language: Английский

Citations

17
Identification of macrophage polarisation and mitochondria-related biomarkers in diabetic retinopathy DOI Creative Commons

Weifeng Liu,

Bin Tong, Jian Xiong

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 6, 2025

The activation of macrophages or microglia in patients' whole body local eyes play significant roles diabetic retinopathy (DR). Mitochondrial function regulates the inflammatory polarization macrophages. Therefore, common mechanism mitochondrial related genes (MRGs) and macrophage polarisation (MPRGs) DR is explored our study to illustrate pathophysiology DR. In this study, using transcriptome data, differentially expressed (DEGs) were firstly analysed for GSE221521, while module MPRGs obtained by weighted gene co-expression network analysis (WGCNA), intersections DEGs with MRGs taken, taken. After that, correlation analyses performed obtain candidate genes. Key Mendelian randomisation (MR) analysis, then biomarkers machine learning combined receiver operating characteristic (ROC) expression validation between control cohorts GSE221521 GSE160306 biomarkers. Finally, subjected immune infiltration set enrichment (GSEA), gene–gene interaction (GGI) analysis. A number 784 taken intersect 1136 782 MPRGs, respectively, after which 89 as MR yielded 13 key clear causal links trends PTAR1 SLC25A34 consistent notable cohort GSE160306. So used Immune showed that activated NK cell Monocyte notably different cohorts, strongest positive correlations cell. Both enriched lysosome insulin signaling pathway. GGI associated prenyltransferase activity prenylation function. This identified two (PTAR1 SLC25A34) explore pathogenesis provide reference targets drug development.

Language: Английский

Citations

2
Nicotinamide riboside attenuates myocardial ischemia-reperfusion injury via regulating SIRT3/SOD2 signaling pathway DOI Open Access
Kai Zhao, Jie Tang,

Hong Xie

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116689 - 116689

Published: May 3, 2024

Ischemic heart disease invariably leads to devastating damage human health. Nicotinamide ribose (NR), as one of the precursors NAD+ synthesis, has been discovered exert a protective role in various neurological and cardiovascular disorders. Our findings demonstrated that pretreatment with 200 mg/kg NR for 3 h significantly reduced myocardial infarct area, decreased levels CK-MB LDH serum, improved cardiac function rats during ischemia-reperfusion (I/R) injury. Meanwhile, 0.5 mM also effectively increased viability release H9c2 cells OGD/R. We had provided evidence could decrease mitochondrial reactive oxygen species (mtROS) production MDA content, enhance SOD activity, thereby mitigating inhibiting apoptosis I/R Further investigations revealed content upregulated SIRT3 protein expression myocardium. Through using small interfering RNA deacetylase activity inhibitor 3-TYP, we confirmed cardioprotective effect on cardiomyocytes was largely dependent inhibition oxidative stress via SIRT3-SOD2 axis. Overall, our study suggested exogenous supplementation mitigated inhibited injury by reducing SIRT3-SOD2-mtROS pathway.

Language: Английский

Citations

9
Involvement of E3 ubiquitin ligase NEDD4-mediated YY1 ubiquitination in alleviating idiopathic pulmonary fibrosis DOI
Lin Chen, Qingxiang Sun,

Ruiming Yue

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 269, P. 131976 - 131976

Published: April 30, 2024

Language: Английский

Citations

8
Sirt6 protects retinal ganglion cells and optic nerve from degeneration during aging and glaucoma DOI Creative Commons
Fan Xia,

Shuizhen Shi,

Erick Palacios

et al.

Molecular Therapy, Journal Year: 2024, Volume and Issue: 32(6), P. 1760 - 1778

Published: April 24, 2024

Glaucoma is characterized by the progressive degeneration of retinal ganglion cells (RGCs) and their axons, its risk increases with aging. Yet comprehensive insights into complex mechanisms are largely unknown. Here, we found that anti-aging molecule Sirt6 was highly expressed in RGCs. Deleting globally or specifically RGCs led to RGC loss optic nerve during aging, despite normal intraocular pressure (IOP), resembling a phenotype normal-tension glaucoma. These detrimental effects were potentially mediated accelerated senescence through Caveolin-1 upregulation induction mitochondrial dysfunction. In mouse models high-tension glaucoma, level decreased after IOP elevation. Genetic overexpression significantly attenuated high tension-induced whereas partial RGC-specific deletion loss. Importantly, therapeutically targeting pharmacological activator AAV2-mediated gene delivery ameliorated IOP-induced degeneration. Together, our studies reveal critical role preventing aging setting stage for further exploration activation as potential therapy

Language: Английский

Citations

7
Activation and inhibition of sirtuins: From bench to bedside DOI Creative Commons
Francesco Fiorentino, Emanuele Fabbrizi, Antonello Mai

et al.

Medicinal Research Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 31, 2024

Abstract The sirtuin family comprises seven NAD + ‐dependent enzymes which catalyze protein lysine deacylation and mono ADP‐ribosylation. Sirtuins act as central regulators of genomic stability gene expression control key processes, including energetic metabolism, cell cycle, differentiation, apoptosis, aging. As a result, all sirtuins play critical roles in cellular homeostasis organism wellness, their dysregulation has been linked to metabolic, cardiovascular, neurological diseases. Furthermore, have shown dichotomous cancer, acting context‐dependent tumor suppressors or promoters. Given role different attracted increasing research interest aimed at developing both activators inhibitors. Indeed, modulation may therapeutic effects many age‐related diseases, diabetes, cardiovascular neurodegenerative disorders, cancer. Moreover, isoform selective modulators increase our knowledge biology aid develop better therapies. Through this review, we provide insights into pharmacology illustrate enzymatic activities biological functions. outline the most relevant terms modes action, structure–activity relationships, pharmacological effects, clinical applications.

Language: Английский

Citations

6
Role of SIRT1 in Potentially Toxic Trace Elements (Lead, Fluoride, Aluminum and Cadmium) Associated Neurodevelopmental Toxicity DOI Creative Commons
Aqsa Fathima, Newly Bagang, Nitesh Kumar

et al.

Biological Trace Element Research, Journal Year: 2024, Volume and Issue: 202(12), P. 5395 - 5412

Published: Feb. 28, 2024

The formation of the central nervous system is a meticulously planned and intricate process. Any modification to this process has potential disrupt structure operation brain, which could result in deficiencies neurological growth. When neurotoxic substances are present during early stages development, they can be exceptionally dangerous. Prenatally, immature brain extremely vulnerable therefore at high risk pregnant women associated with occupational exposures. Lead, fluoride, aluminum, cadmium examples possibly toxic trace elements that have been identified as an environmental concern aetiology number neurodegenerative illnesses. SIRT1, member sirtuin family received most attention for its neuroprotective properties. SIRT1 intriguing therapeutic target since it demonstrates important functions increase neurogenesis cellular lifespan by modulating multiple pathways. It promotes axonal extension, neurite growth, dendritic branching development neurons. Additionally, contributes neurogenesis, synaptic plasticity, memory neuroprotection. This review summarizes possible role signalling pathway potentially -induced neurodevelopmental toxicity, highlighting some molecular pathways such mitochondrial biogenesis, CREB/BDNF PGC-1α/NRF1/TFAM.

Language: Английский

Citations

5