Molecular Mechanisms of Cellular Senescence and Immuno-Senescence: Insights from Model Organisms and Emerging Pathways

Alebachew Molla

doi:doi:10.11648/j.ajbls.20251305.12

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| Peer-Reviewed

Molecular Mechanisms of Cellular Senescence and Immuno-Senescence: Insights from Model Organisms and Emerging Pathways

Alebachew Molla^*

Published in American Journal of Biomedical and Life Sciences (Volume 13, Issue 5)

Received: 25 September 2025 Accepted: 5 October 2025 Published: 30 October 2025

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Abstract

Cellular senescence and immunosenescence encompass critical molecular pathways that govern aging and age-related pathologies. Central to cellular senescence are DNA damage response activation, telomere attrition, chromatin remodeling, metabolic reprogramming, and cytoplasmic DNA sensing via cGAS-STING signaling, which collectively drive cell cycle arrest and the pro-inflammatory senescence-associated secretory phenotype (SASP). Immunosenescence involves progressive deterioration of immune cell function characterized by depleted naive lymphocytes, accumulation of dysfunctional senescent immune cells, and chronic inflammation (inflammaging), creating a feedback loop that exacerbates tissue degeneration and systemic aging. Model organisms such as mice and killifish have been indispensable for unraveling these mechanisms, enabling genetic and functional studies that illuminate senescence dynamics and immune clearance processes. Future research, empowered by multi-omics, single cell sequencing, and artificial intelligence, promises deeper dissection of senescence heterogeneity and tissue-specific pathways, offering biomarkers and therapeutic targets with unprecedented precision. Therapeutic strategies aiming to selectively eliminate or modulate senescent cells through senolytics, senomorphics, and immunomodulatory approaches hold promise to extend health span and ameliorate chronic diseases. However, challenges including senescent cell heterogeneity, context-dependent functions, and biomarker limitations necessitate individualized and careful translation of findings into clinical therapies. Continued interdisciplinary efforts integrating molecular biology, systems medicine, and clinical research will be pivotal in harnessing the full potential of senescence targeting for healthy aging and transformative disease management. This review was conducted to comprehensively compile and discuss the intricate molecular mechanisms underlying cellular senescence and immunosenescence, which are critical processes involved in aging and age-related diseases. The aim of this review article is to comprehensively elucidate the molecular mechanisms underlying cellular senescence and immunosenescence, integrating insights gained from model organism research and emerging signaling pathways.

Published in	American Journal of Biomedical and Life Sciences (Volume 13, Issue 5)
DOI	10.11648/j.ajbls.20251305.12
Page(s)	98-113
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2025. Published by Science Publishing Group

Keywords

Cellular Senescence, Immunosenescence, Senescence-Associated Secretory Phenotype, DNA Damage Response, Senolytic Therapies

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Molla, A. (2025). Molecular Mechanisms of Cellular Senescence and Immuno-Senescence: Insights from Model Organisms and Emerging Pathways. American Journal of Biomedical and Life Sciences, 13(5), 98-113. https://doi.org/10.11648/j.ajbls.20251305.12

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Molla, A. Molecular Mechanisms of Cellular Senescence and Immuno-Senescence: Insights from Model Organisms and Emerging Pathways. Am. J. Biomed. Life Sci. 2025, 13(5), 98-113. doi: 10.11648/j.ajbls.20251305.12

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Molla A. Molecular Mechanisms of Cellular Senescence and Immuno-Senescence: Insights from Model Organisms and Emerging Pathways. Am J Biomed Life Sci. 2025;13(5):98-113. doi: 10.11648/j.ajbls.20251305.12

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@article{10.11648/j.ajbls.20251305.12,
  author = {Alebachew Molla},
  title = {Molecular Mechanisms of Cellular Senescence and Immuno-Senescence: Insights from Model Organisms and Emerging Pathways
},
  journal = {American Journal of Biomedical and Life Sciences},
  volume = {13},
  number = {5},
  pages = {98-113},
  doi = {10.11648/j.ajbls.20251305.12},
  url = {https://doi.org/10.11648/j.ajbls.20251305.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajbls.20251305.12},
  abstract = {Cellular senescence and immunosenescence encompass critical molecular pathways that govern aging and age-related pathologies. Central to cellular senescence are DNA damage response activation, telomere attrition, chromatin remodeling, metabolic reprogramming, and cytoplasmic DNA sensing via cGAS-STING signaling, which collectively drive cell cycle arrest and the pro-inflammatory senescence-associated secretory phenotype (SASP). Immunosenescence involves progressive deterioration of immune cell function characterized by depleted naive lymphocytes, accumulation of dysfunctional senescent immune cells, and chronic inflammation (inflammaging), creating a feedback loop that exacerbates tissue degeneration and systemic aging. Model organisms such as mice and killifish have been indispensable for unraveling these mechanisms, enabling genetic and functional studies that illuminate senescence dynamics and immune clearance processes. Future research, empowered by multi-omics, single cell sequencing, and artificial intelligence, promises deeper dissection of senescence heterogeneity and tissue-specific pathways, offering biomarkers and therapeutic targets with unprecedented precision. Therapeutic strategies aiming to selectively eliminate or modulate senescent cells through senolytics, senomorphics, and immunomodulatory approaches hold promise to extend health span and ameliorate chronic diseases. However, challenges including senescent cell heterogeneity, context-dependent functions, and biomarker limitations necessitate individualized and careful translation of findings into clinical therapies. Continued interdisciplinary efforts integrating molecular biology, systems medicine, and clinical research will be pivotal in harnessing the full potential of senescence targeting for healthy aging and transformative disease management. This review was conducted to comprehensively compile and discuss the intricate molecular mechanisms underlying cellular senescence and immunosenescence, which are critical processes involved in aging and age-related diseases. The aim of this review article is to comprehensively elucidate the molecular mechanisms underlying cellular senescence and immunosenescence, integrating insights gained from model organism research and emerging signaling pathways.
},
 year = {2025}
}

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TY  - JOUR
T1  - Molecular Mechanisms of Cellular Senescence and Immuno-Senescence: Insights from Model Organisms and Emerging Pathways

AU  - Alebachew Molla
Y1  - 2025/10/30
PY  - 2025
N1  - https://doi.org/10.11648/j.ajbls.20251305.12
DO  - 10.11648/j.ajbls.20251305.12
T2  - American Journal of Biomedical and Life Sciences
JF  - American Journal of Biomedical and Life Sciences
JO  - American Journal of Biomedical and Life Sciences
SP  - 98
EP  - 113
PB  - Science Publishing Group
SN  - 2330-880X
UR  - https://doi.org/10.11648/j.ajbls.20251305.12
AB  - Cellular senescence and immunosenescence encompass critical molecular pathways that govern aging and age-related pathologies. Central to cellular senescence are DNA damage response activation, telomere attrition, chromatin remodeling, metabolic reprogramming, and cytoplasmic DNA sensing via cGAS-STING signaling, which collectively drive cell cycle arrest and the pro-inflammatory senescence-associated secretory phenotype (SASP). Immunosenescence involves progressive deterioration of immune cell function characterized by depleted naive lymphocytes, accumulation of dysfunctional senescent immune cells, and chronic inflammation (inflammaging), creating a feedback loop that exacerbates tissue degeneration and systemic aging. Model organisms such as mice and killifish have been indispensable for unraveling these mechanisms, enabling genetic and functional studies that illuminate senescence dynamics and immune clearance processes. Future research, empowered by multi-omics, single cell sequencing, and artificial intelligence, promises deeper dissection of senescence heterogeneity and tissue-specific pathways, offering biomarkers and therapeutic targets with unprecedented precision. Therapeutic strategies aiming to selectively eliminate or modulate senescent cells through senolytics, senomorphics, and immunomodulatory approaches hold promise to extend health span and ameliorate chronic diseases. However, challenges including senescent cell heterogeneity, context-dependent functions, and biomarker limitations necessitate individualized and careful translation of findings into clinical therapies. Continued interdisciplinary efforts integrating molecular biology, systems medicine, and clinical research will be pivotal in harnessing the full potential of senescence targeting for healthy aging and transformative disease management. This review was conducted to comprehensively compile and discuss the intricate molecular mechanisms underlying cellular senescence and immunosenescence, which are critical processes involved in aging and age-related diseases. The aim of this review article is to comprehensively elucidate the molecular mechanisms underlying cellular senescence and immunosenescence, integrating insights gained from model organism research and emerging signaling pathways.

VL  - 13
IS  - 5
ER  -

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Alebachew Molla

Department of Biotechnology, Wolaita Sodo University, Wolaita, Ethiopia

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http://orcid.org/0009-0004-3180-2775

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Molla, A. (2025). Molecular Mechanisms of Cellular Senescence and Immuno-Senescence: Insights from Model Organisms and Emerging Pathways. American Journal of Biomedical and Life Sciences, 13(5), 98-113. https://doi.org/10.11648/j.ajbls.20251305.12

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ACS Style

Molla, A. Molecular Mechanisms of Cellular Senescence and Immuno-Senescence: Insights from Model Organisms and Emerging Pathways. Am. J. Biomed. Life Sci. 2025, 13(5), 98-113. doi: 10.11648/j.ajbls.20251305.12

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AMA Style

Molla A. Molecular Mechanisms of Cellular Senescence and Immuno-Senescence: Insights from Model Organisms and Emerging Pathways. Am J Biomed Life Sci. 2025;13(5):98-113. doi: 10.11648/j.ajbls.20251305.12

Copy | Download

@article{10.11648/j.ajbls.20251305.12,
  author = {Alebachew Molla},
  title = {Molecular Mechanisms of Cellular Senescence and Immuno-Senescence: Insights from Model Organisms and Emerging Pathways
},
  journal = {American Journal of Biomedical and Life Sciences},
  volume = {13},
  number = {5},
  pages = {98-113},
  doi = {10.11648/j.ajbls.20251305.12},
  url = {https://doi.org/10.11648/j.ajbls.20251305.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajbls.20251305.12},
  abstract = {Cellular senescence and immunosenescence encompass critical molecular pathways that govern aging and age-related pathologies. Central to cellular senescence are DNA damage response activation, telomere attrition, chromatin remodeling, metabolic reprogramming, and cytoplasmic DNA sensing via cGAS-STING signaling, which collectively drive cell cycle arrest and the pro-inflammatory senescence-associated secretory phenotype (SASP). Immunosenescence involves progressive deterioration of immune cell function characterized by depleted naive lymphocytes, accumulation of dysfunctional senescent immune cells, and chronic inflammation (inflammaging), creating a feedback loop that exacerbates tissue degeneration and systemic aging. Model organisms such as mice and killifish have been indispensable for unraveling these mechanisms, enabling genetic and functional studies that illuminate senescence dynamics and immune clearance processes. Future research, empowered by multi-omics, single cell sequencing, and artificial intelligence, promises deeper dissection of senescence heterogeneity and tissue-specific pathways, offering biomarkers and therapeutic targets with unprecedented precision. Therapeutic strategies aiming to selectively eliminate or modulate senescent cells through senolytics, senomorphics, and immunomodulatory approaches hold promise to extend health span and ameliorate chronic diseases. However, challenges including senescent cell heterogeneity, context-dependent functions, and biomarker limitations necessitate individualized and careful translation of findings into clinical therapies. Continued interdisciplinary efforts integrating molecular biology, systems medicine, and clinical research will be pivotal in harnessing the full potential of senescence targeting for healthy aging and transformative disease management. This review was conducted to comprehensively compile and discuss the intricate molecular mechanisms underlying cellular senescence and immunosenescence, which are critical processes involved in aging and age-related diseases. The aim of this review article is to comprehensively elucidate the molecular mechanisms underlying cellular senescence and immunosenescence, integrating insights gained from model organism research and emerging signaling pathways.
},
 year = {2025}
}

Copy | Download

TY  - JOUR
T1  - Molecular Mechanisms of Cellular Senescence and Immuno-Senescence: Insights from Model Organisms and Emerging Pathways

AU  - Alebachew Molla
Y1  - 2025/10/30
PY  - 2025
N1  - https://doi.org/10.11648/j.ajbls.20251305.12
DO  - 10.11648/j.ajbls.20251305.12
T2  - American Journal of Biomedical and Life Sciences
JF  - American Journal of Biomedical and Life Sciences
JO  - American Journal of Biomedical and Life Sciences
SP  - 98
EP  - 113
PB  - Science Publishing Group
SN  - 2330-880X
UR  - https://doi.org/10.11648/j.ajbls.20251305.12
AB  - Cellular senescence and immunosenescence encompass critical molecular pathways that govern aging and age-related pathologies. Central to cellular senescence are DNA damage response activation, telomere attrition, chromatin remodeling, metabolic reprogramming, and cytoplasmic DNA sensing via cGAS-STING signaling, which collectively drive cell cycle arrest and the pro-inflammatory senescence-associated secretory phenotype (SASP). Immunosenescence involves progressive deterioration of immune cell function characterized by depleted naive lymphocytes, accumulation of dysfunctional senescent immune cells, and chronic inflammation (inflammaging), creating a feedback loop that exacerbates tissue degeneration and systemic aging. Model organisms such as mice and killifish have been indispensable for unraveling these mechanisms, enabling genetic and functional studies that illuminate senescence dynamics and immune clearance processes. Future research, empowered by multi-omics, single cell sequencing, and artificial intelligence, promises deeper dissection of senescence heterogeneity and tissue-specific pathways, offering biomarkers and therapeutic targets with unprecedented precision. Therapeutic strategies aiming to selectively eliminate or modulate senescent cells through senolytics, senomorphics, and immunomodulatory approaches hold promise to extend health span and ameliorate chronic diseases. However, challenges including senescent cell heterogeneity, context-dependent functions, and biomarker limitations necessitate individualized and careful translation of findings into clinical therapies. Continued interdisciplinary efforts integrating molecular biology, systems medicine, and clinical research will be pivotal in harnessing the full potential of senescence targeting for healthy aging and transformative disease management. This review was conducted to comprehensively compile and discuss the intricate molecular mechanisms underlying cellular senescence and immunosenescence, which are critical processes involved in aging and age-related diseases. The aim of this review article is to comprehensively elucidate the molecular mechanisms underlying cellular senescence and immunosenescence, integrating insights gained from model organism research and emerging signaling pathways.

VL  - 13
IS  - 5
ER  -

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