Current aspects of targeting cellular senescence for the therapy of neurodegenerative diseases

Ravindran Jaganathan (Co-first author), Ashok Iyaswamy* (Co-first author), Senthilkumar Krishnamoorthi, Abhimanyu Thakur, Siva Sundara Kumar Durairajan, Chuanbin Yang*, Dapkupar Wankhar*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Introduction: Aging is a normal process causing deterioration in normal brain function and is inevitable. The aging process is described by the buildup of senescent cells and a decline in the ability to maintain essential homeostatic functions. Cellular aging represents a critical process where cells undergo cell cycle arrest in response to stress and neuronal damage. Many neurodegenerative disorders are closely linked to cellular senescence caused by oxidative stress, ROS generation, and DNA damage. Therefore, targeting cellular senescence is essential for the therapy of neurodegenerative disorders.

Methods: This review outlines the understanding of cellular senescence, its role in the aging process, signaling pathways, autophagy, lysosomal biogenesis, and its contribution to various neurodegenerative disorders.

Results: The findings highlight the relationship between cellular senescence and neurodegenerative disorders, emphasizing its pathological role. Current evidence indicates that senolytic drugs, notably phytochemicals such as dasatinib, quercetin, and fisetin, could serve as therapeutic approaches to target senescent cells and improve outcomes in neurodegenerative illnesses.

Discussion: This review conclusively addresses the possibility of senolytic interventions for the treatment of neurodegenerative diseases. It will encourage researchers to identify novel compounds or phytochemicals that could be used as senolytic drugs for treating numerous neurodegenerative disorders.

Original languageEnglish
Article number1627921
Number of pages16
JournalFrontiers in Aging Neuroscience
Volume17
DOIs
Publication statusPublished - 25 Sept 2025

User-Defined Keywords

  • aging
  • cellular senescence
  • DNA damage
  • neurodegenerative diseases
  • senolytic drugs

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