Castration Model Illuminates Sex Differences in Healthy Aging: Insights from Metabolome and Transcriptome Analyses DOI Creative Commons
Jianjun Jiang, Na Ge, Yuzhi Wang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 28, 2023

ABSTRACT Background Sex, as a critical biological variable, has historically been underappreciated, despite the pervasive influence of sexual dimorphism across physiological and pathological processes. A significant obstacle to advancing sex-biased research is absence an effective animal model. In recent years, castration emerged potential model for elucidating sex-based differences in context healthy aging, where it shown equalize lifespan growth trajectories genetically diverse mice. However, molecular shifts induced by common laboratory models, such C57BL/6 mice, broader applicability this other sex-related contexts remain largely unexplored. Methods We employed multi-omics observational analyses investigate changes associated with sex hormones following castration. analyzed serum, kidney, liver samples from 12-week-old 18-month-old castrated male alongside intact female counterparts. The was further applied assess cisplatin-induced toxicity age-related cognitive decline comparison unaltered controls. Results LC-MS/MS metabolomics revealed that males exhibited substantial alterations steroid hormone levels increased concentrations antioxidant compounds, taurine, identical diets. Integrated metabolome-transcriptome analysis confirmed distinct patterns lipid peroxidation oxidative stress sham-operated female, male, Histopathological evaluations cisplatin treatment aging-related behavioral tests demonstrated model’s utility investigating sex-dependent drug decline. These findings underscored role modulating both defense mechanisms performance. Conclusion This study provides systematic spectrum on demonstrates its capacity feminize metabolic transcriptomic profiles, establishing valuable tool exploring hormone-driven differences. Our lay groundwork mechanistic studies broaden applications biomedical domains.

Language: Английский

Transcriptomic Hallmarks of Mortality Reveal Universal and Specific Mechanisms of Aging, Chronic Disease, and Rejuvenation DOI
Alexander Tyshkovskiy,

Daria Kholdina,

Kejun Ying

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 7, 2024

SUMMARY Health is strongly affected by aging and lifespan-modulating interventions, but the molecular mechanisms of mortality regulation remain unclear. Here, we conducted an RNA-seq analysis mice subjected to 20 compound treatments in Interventions Testing Program (ITP). By integrating it with data from over 4,000 rodent tissues representing responses genetic, pharmacological, dietary interventions established survival data, developed robust multi-tissue transcriptomic biomarkers mortality, capable quantifying change lifespan both short-lived long-lived models. These tools were further extended single-cell human demonstrating common across cell types species. Via a network analysis, identified annotated 26 co-regulated modules longevity tissues, interpretable module-specific clocks that capture aging- mortality-associated phenotypes functional components, including, among others, inflammatory response, mitochondrial function, lipid metabolism, extracellular matrix organization. captured characterized acceleration biological age induced progeria models chronic diseases rodents humans. They also revealed rejuvenation heterochronic parabiosis, early embryogenesis, cellular reprogramming, highlighting universal signatures shared age-related disease. included Cdkn1a Lgals3 , whose plasma levels demonstrated strong association all-cause disease incidence risk factors, such as obesity hypertension. Overall, this study uncovers hallmarks mammalian organs, types, species rejuvenation, exposing fundamental longevity.

Language: Английский

Citations

8
Senescent endothelial cell-derived Galectin 3 promotes silicosis through endothelial-fibroblast and endothelial-macrophage crosstalk DOI

Demin Cheng,

Wenxiu Lian,

Xinying Jia

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: 489, P. 137605 - 137605

Published: Feb. 13, 2025

Language: Английский

Citations

1
Senescent alveolar type II epithelial cells-secreted GDF15 promotes silicosis progression via interfering intercellular communication DOI Creative Commons

Wenxiu Lian,

Demin Cheng,

Wenqing Sun

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 292, P. 117917 - 117917

Published: Feb. 21, 2025

Language: Английский

Citations

1
Use of Nicotinamide Mononucleotide as Non-Natural Cofactor DOI Open Access
Tahseena Naaz, Beom Soo Kim

Catalysts, Journal Year: 2025, Volume and Issue: 15(1), P. 37 - 37

Published: Jan. 3, 2025

Nicotinamide mononucleotide (NMN) has emerged as a promising non-natural cofactor with significant potential to transform biocatalysis, synthetic biology, and therapeutic applications. By modulating NAD⁺ metabolism, NMN offers unique advantages in enzymatic reactions, metabolic engineering, regenerative medicine. This review provides comprehensive analysis of NMN’s biochemical properties, mechanisms action, diverse Emphasis is placed on its role addressing challenges multi-enzyme cascades, biofuel production, the synthesis high-value chemicals. The paper also highlights critical research gaps, including need for scalable methods, improved integration into systems, toxicity studies use. Emerging technologies such AI-driven enzyme design CRISPR-based genome engineering are discussed transformative tools optimizing NMN-dependent pathways. Furthermore, synergistic biology innovations, cell-free systems dynamic regulatory networks, explored, paving way precise modular biotechnological solutions. Looking forward, versatility positions it pivotal tool advancing sustainable bioprocessing precision Addressing current limitations through interdisciplinary approaches will enable redefine boundaries innovation. serves roadmap leveraging across scientific industrial domains.

Language: Английский

Citations

0
Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD + synthesis via enterohepatic circulation DOI Creative Commons
Keisuke Yaku, Sailesh Palikhe, Tooba Iqbal

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(12)

Published: March 21, 2025

Decreased nicotinamide adenine dinucleotide (oxidized form) (NAD + ) levels are reportedly associated with several aging-related disorders. Thus, supplementation NAD precursors, such as mononucleotide (NMN) and riboside (NR), exhibits beneficial effects against these However, the in vivo metabolic pathways of NMN NR remain to be elucidated. In this study, we comprehensively analyzed fate orally intravenously administered mice using metabolomics. We found that only a small portion was directly absorbed from intestine most them underwent gut microbiota–mediated deamidation conversion nicotinic acid (NA). Moreover, were rapidly degraded into secreted bile followed by NA microbiota. enterohepatic circulated is preferentially used liver. These findings showed indirectly converted via unexpected pathways.

Language: Английский

Citations

0
Rapid nicotinamide mononucleotide detection using a dual-ligand Eu-MOF-based ratiometric fluorescence sensor DOI

Yong-Shun Zhai,

Yue-Hong Pang,

Yongwei Feng

et al.

Food Bioscience, Journal Year: 2025, Volume and Issue: unknown, P. 106554 - 106554

Published: April 1, 2025

Language: Английский

Citations

0
High-Level Production of Nicotinamide Mononucleotide by Engineered Escherichia Coli DOI

Jiajia Gan,

Xiuzhen Chen,

Yongzhi He

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

Nicotinamide mononucleotide (NMN), a key precursor of NAD

Language: Английский

Citations

3
β-Nicotinamide mononucleotide supplementation prolongs the lifespan of prematurely aged mice and protects colon function in ageing mice DOI Creative Commons
Yanrou Gu,

Lidan Gao,

Jiamin He

et al.

Food & Function, Journal Year: 2024, Volume and Issue: 15(6), P. 3199 - 3213

Published: Jan. 1, 2024

NMN prolonged the life span and delayed senescence in premature ageing mice.

Language: Английский

Citations

2
Improved Physical Performance Parameters in Patients Taking Nicotinamide Mononucleotide (NMN): A Systematic Review of Randomized Control Trials DOI Open Access
Jimmy Wen,

Burhaan Syed,

S.Y. Kim

et al.

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Nicotinamide adenine dinucleotide (NAD+) is essential in the proper function of many cellular processes human body. The purpose this review to investigate effect nicotinamide mononucleotide (NMN), a NAD+ precursor, on physical performance and evaluate safety profile supplementation. A systematic search criteria following guidelines from Preferred Reporting Items for Systematic Reviews Meta-Analyses (PRISMA) was performed four databases randomized controlled trials NMN Study variables included title, author, publication date, study year, number patients, dosage, mean age, follow-up time, pre- post-intervention reported outcomes, rates complications. Ten studies, including 437 with age 58.0 years (35.1 81.1 years) time 9.6 weeks (4 12 weeks) were study. dosages ranged 150 1200 mg/day. Mean pre-intervention grip strength (two studies) skeletal mass index 29.9 kilograms (kg) (range: 21.4-40.1 kg) 7.4 kg/m2 6.9-7.65 kg/m2), respectively. 30.5 kg 21.7-41.9 (6.8-7.64 There no serious adverse effects observed. Moreover, side effects, they determined be independent Therefore, patients taking supplementation demonstrated non-significantly improved parameters. well tolerated

Language: Английский

Citations

1
Quantitative dynamics of intracellular NMN by genetically encoded biosensor DOI
Liuqing Chen, Pei Wang, Guan Huang

et al.

Biosensors and Bioelectronics, Journal Year: 2024, Volume and Issue: 267, P. 116842 - 116842

Published: Oct. 10, 2024

Language: Английский

Citations

1