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

Esraa M Mosalam1, Mahmoud S Abdallah1, Ahmed R Gardouh2

  • 1Department of PharmD, Faculty of Pharmacy, Jadara University, Irbid, 21110, Jordan.

Biogerontology
|August 7, 2026
PubMed

Insights

Silent information regulator sirtuin 1 (SIRT1) plays a key role in brain aging and genomic stability. SIRT1 activators like resveratrol, metformin, and statins show neuroprotective effects against aging by reducing oxidative stress and inflammation.

Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • Aging increases DNA repair errors and genomic instability, leading to oxidative stress and brain aging.
  • Neuronal senescence is a primary driver of brain aging, causing cognitive impairment and memory loss.
  • Silent information regulator sirtuin 1 (SIRT1), a histone deacetylase, is crucial for genomic stability and is expressed in brain regions vital for development and senescence control.

Purpose of the Study:

  • To review the role of SIRT1 in brain aging.
  • To summarize compounds that modulate SIRT1 activity and their mechanisms.
  • To explore therapeutic potential for neurodegenerative diseases.

Main Methods:

  • Narrative review of existing literature.
  • Critical evaluation of SIRT1's function in brain aging.
  • Analysis of mechanistic pathways of SIRT1 modulators.

Main Results:

  • SIRT1 activators (resveratrol, metformin, statins) demonstrate neuroprotective effects.
  • These compounds mitigate brain aging by regulating oxidative stress and inflammation.
  • Modulation occurs through downstream signaling pathways.

Conclusions:

  • SIRT1 is a potential therapeutic target for brain aging and neurodegenerative diseases.
  • Compounds activating SIRT1 offer a promising strategy for neuroprotection.
  • Further research into SIRT1 pathways can guide the development of novel treatments.
Keywords:
AgingBrain agingGeroprotector effectsSIRT1 modulators

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