SIRT1 in brain aging: molecular mechanisms and therapeutic potential of pharmacological and natural modulators.

IF 5.3 4区医学 Q1 GERIATRICS & GERONTOLOGY

Biogerontology Pub Date : 2026-08-07 DOI:10.1007/s10522-026-10480-7

Esraa M Mosalam, Mahmoud S Abdallah, Ahmed R Gardouh, Eman Hamza, Mostafa M Bahaa, Mahmoud Nazih, Reham A Al-Dhelaan, Noha Kamal

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Abstract

Aging is a multifactorial process affects different tissues and organs and is modulated by genetic and environmental factors. In aging, the frequency of DNA repair errors and genomic instability are augmented. Depletion of endogenous antioxidant capacity during aging promotes the development of oxidative stress which triggers oxidative stress-induced DNA injury. Brain aging is manifested by cognitive impairment and memory disorders. Development of neuronal senescence is the major pathway in the progression of brain aging. Silent information regulator sirtuin 1 (SIRT1) is a class III histone deacetylase plays a critical role in genomic stability during aging. SIRT1 is highly expressed in specific brain regions involved in energy expenditure and metabolic activity that is necessary for brain development and control of brain senescence. Therefore, SIRT1 may have neuroprotective effects against brain aging and related neurodegenerative diseases. This narrative review aims to critically evaluate the role of SIRT1 in brain aging and to summarize current evidence on compounds that directly or indirectly modulate SIRT1 activity, with a focus on their mechanistic pathways and potential therapeutic implications. Findings of the present review highlighted that SIRT1 activators such as resveratrol, metformin and statins have neuroprotective effects against brain aging by regulating inflammatory and oxidative stress disorders through modulation of downstream signaling pathways.

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脑老化中的SIRT1：分子机制和药物和天然调节剂的治疗潜力。

衰老是一个影响不同组织和器官的多因素过程，受遗传和环境因素的调节。在衰老过程中，DNA修复错误和基因组不稳定性的频率增加。衰老过程中内源性抗氧化能力的消耗促进氧化应激的发展，从而引发氧化应激诱导的DNA损伤。大脑老化表现为认知障碍和记忆障碍。神经元衰老的发生是脑衰老的主要途径。沉默信息调节因子SIRT1 （Silent information regulator SIRT1）是一种III类组蛋白去乙酰化酶，在衰老过程中对基因组稳定性起关键作用。SIRT1在参与能量消耗和代谢活动的特定大脑区域高度表达，这是大脑发育和控制大脑衰老所必需的。因此，SIRT1可能对脑老化及相关神经退行性疾病具有神经保护作用。本文旨在批判性地评估SIRT1在脑衰老中的作用，并总结目前关于直接或间接调节SIRT1活性的化合物的证据，重点是它们的机制途径和潜在的治疗意义。本综述的研究结果强调SIRT1激活剂如白藜芦醇、二甲双胍和他汀类药物通过调节下游信号通路调节炎症和氧化应激障碍，具有抗脑衰老的神经保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biogerontology 医学-老年医学

CiteScore

8.00

自引率

4.40%

发文量

审稿时长

>12 weeks

期刊介绍： The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments. Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.