Chronic inflammation and the hallmarks of aging

Molecular Metabolism, Год журнала: 2023, Номер 74, С. 101755 - 101755

Опубликована: Июнь 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.

Язык: Английский

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NAD metabolism: Role in senescence regulation and aging

Aging Cell, Год журнала: 2023, Номер 23(1)

Опубликована: Июль 9, 2023

Abstract The geroscience hypothesis proposes that addressing the biology of aging could directly prevent onset or mitigate severity multiple chronic diseases. Understanding interplay between key aspects biological hallmarks is essential in delivering promises hypothesis. Notably, nucleotide nicotinamide adenine dinucleotide (NAD) interfaces with several aging, including cellular senescence, and changes NAD metabolism have been shown to be involved process. relationship senescence appears complex. On one hand, accumulation DNA damage mitochondrial dysfunction induced by low + can promote development senescence. other state occurs during may inhibit SASP as this secretory phenotype are both highly metabolically demanding. However, date, impact on progression has not fully characterized. Therefore, explore implications replacement therapies, it consider their interactions We propose a comprehensive understanding boosting strategies senolytic agents necessary advance field.

Язык: Английский

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Astragalin from Thesium chinense: A Novel Anti-Aging and Antioxidant Agent Targeting IGFR/CD38/Sirtuins

Antioxidants, Год журнала: 2024, Номер 13(7), С. 859 - 859

Опубликована: Июль 18, 2024

Astragalin (AG), a typical flavonoid found in Thesium chinense Turcz (T. chinense), is abundant various edible plants and possesses high nutritional value, as well antioxidant antibacterial effects. In this study, we initially predicted the mechanism of action AG with two anti-aging antioxidant-related protein targets (CD38 IGFR) by molecular docking dynamics simulation techniques. Subsequently, examined effects Caenorhabditis elegans (C. elegans), zebrafish, verified related mechanisms. C. elegans, synergistically extended lifespan up-regulating expression daf-16 through inhibiting daf-2/IGFR also activating AMPK MAPK pathways to up-regulate sir-2.1, sir-2.4, skn-1. oxidatively damaged zebrafish embryos, demonstrated synergistic effect augmenting resistance embryos oxidative stress levels SIRT1 SIRT6 within system via suppression CD38 enzymatic activity then IGFR SIRT6. These findings highlight properties indicate its potential application supplementary ingredient aquaculture for enhancing fish health growth.

Язык: Английский

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Dietary Polyphenols as Anti-Aging Agents: Targeting the Hallmarks of Aging

Nutrients, Год журнала: 2024, Номер 16(19), С. 3305 - 3305

Опубликована: Сен. 29, 2024

Background: Aging is a natural biological process influenced by multiple factors and significant contributor to various chronic diseases. Slowing down the aging extending health span have been pursuits of scientific field. Methods: Examination effects dietary polyphenols on hallmarks such as genomic instability, telomere attrition, epigenetic alterations, loss proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, inflammation, dysbiosis. Results: Polyphenols, abundant in nature, exhibit numerous activities, including antioxidant effects, free radical scavenging, neuroprotection, anti-aging properties. These compounds are generally safe effective potentially slowing preventing age-related disorders. Conclusions: The review encourages development novel therapeutic strategies using create holistic therapies nutritional supplements.

Язык: Английский

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Hydrogen sulfide preserves the function of senescent endothelium through SIRT2 mediated inflammatory inhibition

Journal of Molecular and Cellular Cardiology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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PRMT1 Upregulates SIRT6 by Enhancing Arginine Methylation of E2F7 to Inhibit Vascular Smooth Muscle Cell Senescence in Aortic Dissection

The FASEB Journal, Год журнала: 2025, Номер 39(9)

Опубликована: Апрель 29, 2025

ABSTRACT Aortic dissection (AD) is a highly alarming clinical condition of the aorta, with significant mortality rate. Vascular smooth muscle cell (VSMC) senescence dominantly promotes AD progression. This study planned to clarify exact functions and mechanisms protein arginine methyltransferase 1 (PRMT1), E2F7, Sirtuin 6 (SIRT6) in VSMC model. Angiotensin II (Ang II) β‐Aminopropionitrile (BAPN) were used treat VSMCs or C57BL/6J mice establish vitro vivo Protein expressions examined by western blot, IHC, IF staining. Histological change was monitored using H&E senescence‐associated‐β‐galactosidase (SA‐β‐gal) Enzyme‐Linked Immunosorbent Assay (ELISA) assays utilized evaluate senescence‐associated secretory phenotype markers' levels. The binding interactions between E2F7 SIRT6 PRMT1 verified luciferase reporter, ChIP Co‐IP, GST‐pull‐down analysis. ubiquitination levels assessed assays. PRMT1, decreased Ang II‐treated Moreover, repressed transcriptionally regulating silencing promoted under II. Further, PRMT1‐mediated methylation could maintain stability E2F7. restrained via E2F7/SIRT6 axis enhanced leading upregulation SIRT6, thereby inhibiting

Язык: Английский

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Immune aging and infectious diseases

Chinese Medical Journal, Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

Abstract The rise in global life expectancy has led to an increase the older population, presenting significant challenges managing infectious diseases. Aging affects innate and adaptive immune systems, resulting chronic low-grade inflammation (inflammaging) function decline (immunosenescence). These changes would impair defense mechanisms, susceptibility infections reduce vaccine efficacy adults. Cellular senescence exacerbates these issues by releasing pro-inflammatory factors, further perpetuating inflammation. Moreover, comorbidities, such as cardiovascular disease diabetes, which are common adults, amplify dysfunction, while immunosuppressive medications complicate responses infections. This review explores molecular cellular mechanisms driving inflammaging immunosenescence, focusing on genomic instability, telomere attrition, mitochondrial dysfunction. Additionally, we discussed how aging-associated alterations influence bacterial, viral, parasitic evaluated emerging antiaging strategies, aimed at mitigating effects improve health outcomes aging population.

Язык: Английский

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ADSCs encapsulated in Gelatin methacrylate substrate promotes the repair of peripheral nerve injury by SIRT6/PGC-1α pathway

Regenerative Therapy, Год журнала: 2024, Номер 26, С. 671 - 682

Опубликована: Июнь 1, 2024

Peripheral nerve injury is a prevalent disease but the spontaneous recovery of function protracted and incomplete. Given damaging stem cells fragile intra-neural structures in course cell transplantation, our study tried to investigate whether encapsulating adipose derived mesenchymal (ADSCs) with GelMA could achieve better repair peripheral injury. PC-12 were cultured on surface ADSCs 3D co-culture system was constructed. CCK-8, Real-Time PCR, ELISA, Immunofluorescent Assay Western Blot used evaluate functionality this system. Ultimately, conduit containing linked between two ends an injured nerve. encapsulated 5% GeIMA had activity than 10% GeIMA. Furthermore, viability also without The expression SIRT6 PGC-1α prominently promoted, entry nuclear more obvious After silencing SIRT6, protein level inhibited, significantly reduced, suggesting that upregulated induce protein, thereby achieving impact cells.

Язык: Английский

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CD38 modulates cytokine secretion by NK cells through the Sirt1/NF-κB pathway, suppressing immune surveillance in colorectal cancer

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Ноя. 20, 2024

Tregs and M2-type macrophages are essential for immune surveillance. CD38 + NK cells involved in immunoregulation by modulating cytokine secretion. This study investigated how NKs affect colorectal cancer (CRC). Higher proportions of were detected bloods tumor tissues CRC patients than that the samples from healthy controls (HCs). Compared with HCs, promoted differentiation CD4 T cells, secreted increased levels IL-10, TGF-β TNF-α decreased IFN-γ. expressed higher CD38, NF-κB acetyl-NF-κB lower Sirt1. When treated anti-CD38 monoclonal antibody, above trends reversed. treatment inhibitor also showed opposite effects on secretion T-cell differentiation. After a Sirt1 activator, signaling was inhibited these NKs, whereas activated signaling. The supernatants culture M0 macrophage polarization to M2-type. We suggest modulates through Sirt1/NF-κB pathway, thereby suppressing surveillance tumorigenesis.

Язык: Английский

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Hepatic Sirt6 protects against cholestatic liver disease primarily via inhibiting bile acid synthesis rather than antioxidation or triggering mitochondrial biogenesis

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Фев. 7, 2024

Abstract Cholestatic liver disease, caused by accumulation of hazardous bile acids in the liver, may result cirrhosis, fibrosis, or failure. Activation Sirt6 prevents cholestasis-associated pathological events such as oxidative stress and mitochondrial biogenesis disorders inhibits acid synthesis to alleviate cholestatic injury. However, it is still uncertain which route responsible for therapeutic effect reducing cholestasis. For this reason, we administered liver-specific knockout mice with N-Acetylcysteine, Keap1-Nrf2-IN-1 acadesine remove and/or trigger after disease modeling, but these measures did not significantly improve symptoms. Unlike antioxidant triggers biogenesis, MDL801, a agonist suppressing CYP7A1 expression down-regulating serum levels, exhibited favorable effects. It suggests that inhibition hepatic main pathway alleviates disease. These findings provide solid basis possible application agonists treatment

Язык: Английский

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