Scholarlink

<p>Aging features a gradual decline in genomic integrity, epigenetic fidelity, and cellular homeostasis, driving the onset of chronic pathologies such as cancer, neurodegeneration, and metabolic disease. Growth arrest and DNA damage–inducible 45 alpha (GADD45α) functions as a pivotal stress-response mediator, coordinating DNA repair, cell-cycle arrest, oxidative stress defence, mitochondrial quality control, and chromatin remodeling. Researchers have extensively studied GADD45α in tumor suppression, but its roles in healthy aging and age-related disorders remain underexplored. Here, we provide a comprehensive synthesis of recent findings illuminating GADD45α’s contributions to aging biology. We detail its engagement with nucleotide and base excision repair pathways to preserve genome stability, enforce G₂/M checkpoints to prevent damaged DNA propagation, and promote mitochondrial resilience under oxidative challenge. We then examine how GADD45α modulates epigenetic landscapes, mitigating age-associated DNA methylation drift and sustaining chromatin plasticity, and highlight its emerging neuroprotective actions in Alzheimer’s and Parkinson’s models. Integrating multi-omics analyses, in vivo rodent investigations, and Drosophila lifespan assays, we establish GADD45α as a dynamic biomarker of cellular aging and a promising geroprotective target. Finally, we discuss translational strategies to harness GADD45α activity, ranging from small-molecule enhancers and epigenetic modifiers to precision gene-editing to reinforce DNA repair capacity, delay senescence onset, and extend organismal healthspan. This review reframes GADD45α from a cancer-centric effector to a versatile regulator of aging processes, underscoring its therapeutic potential for promoting healthy longevity.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Translational potential of GADD45α: biomarker and therapeutic target in age-associated neurodegeneration and longevity

  • 期刊论文

  • 发表日期：

    2025年6月30日

查看全文
  • Imran Kazmi,
  • Fahad A. Al-Abbasi,
  • Mustafa Zeyadi,
  • Misbahuddin Rafeeq,
  • Alaa Hamed Habib,
  • Johar Iqbal,
  • Sami I. Alzarea,
  • Omar Awad Alsaidan,
  • Muhammad Shahid Nadeem

摘要

Aging features a gradual decline in genomic integrity, epigenetic fidelity, and cellular homeostasis, driving the onset of chronic pathologies such as cancer, neurodegeneration, and metabolic disease. Growth arrest and DNA damage–inducible 45 alpha (GADD45α) functions as a pivotal stress-response mediator, coordinating DNA repair, cell-cycle arrest, oxidative stress defence, mitochondrial quality control, and chromatin remodeling. Researchers have extensively studied GADD45α in tumor suppression, but its roles in healthy aging and age-related disorders remain underexplored. Here, we provide a comprehensive synthesis of recent findings illuminating GADD45α’s contributions to aging biology. We detail its engagement with nucleotide and base excision repair pathways to preserve genome stability, enforce G₂/M checkpoints to prevent damaged DNA propagation, and promote mitochondrial resilience under oxidative challenge. We then examine how GADD45α modulates epigenetic landscapes, mitigating age-associated DNA methylation drift and sustaining chromatin plasticity, and highlight its emerging neuroprotective actions in Alzheimer’s and Parkinson’s models. Integrating multi-omics analyses, in vivo rodent investigations, and Drosophila lifespan assays, we establish GADD45α as a dynamic biomarker of cellular aging and a promising geroprotective target. Finally, we discuss translational strategies to harness GADD45α activity, ranging from small-molecule enhancers and epigenetic modifiers to precision gene-editing to reinforce DNA repair capacity, delay senescence onset, and extend organismal healthspan. This review reframes GADD45α from a cancer-centric effector to a versatile regulator of aging processes, underscoring its therapeutic potential for promoting healthy longevity.