Executive Summary

Cellular senescence is a permanent state of cell cycle arrest that influences aging and age-related diseases. It contributes to tissue regeneration, wound healing, and embryonic development, and serves as a tumor suppressor mechanism. Senescent cells accumulate with age, secreting pro-inflammatory factors, the senescence-associated secretory phenotype (SASP), and exacerbate various pathologies by promoting chronic inflammation. Recent advancements focus on the identification and therapeutic targeting of senescent cells to improve health span and tackle age-related diseases. The development of biomarkers for senescent cells is pivotal for both research and clinical applications. However, identifying specific, reliable, and universally accepted biomarkers remains a challenge. Despite advances in the field, details concerning the senescence process in different cell types and the heterogeneity of senescent cell phenotypes complicate therapeutic strategies. The concept of senotherapeutics, including both senolytics and senomorphics, emerges as promising interventions to selectively target senescent cells and ameliorate the detrimental aspects of senescence.

Research History

Cellular senescence research has expanded from a cellular perspective to understanding its impact on organismal aging and disease. Foundational papers in the field identified the phenomenon of senescence and its role in tumor suppression (Campisi, Annual Review of Physiology, 2013) and introduced the concept of the SASP (Coppe et al., PLOS Biology, 2008). The selection of these papers is based on their contribution to defining cellular senescence and identifying the SASP as a key mediator of senescence effects on tissue microenvironment.

Recent Advancements

Recent advancements in cellular senescence research encompass the genomic and proteomic profiling of senescent cells, development of senescent cell biomarkers, and understanding the complexity and heterogeneity of the senescence program. A relevant paper by Hernandez-Segura et al. (Trends in Cell Biology, 2018) discusses the molecular regulators of senescence phenotypes and their use in identifying senescent cells. This paper is chosen for its insights into the biological markers of senescence.

Current Challenges

Noteworthy challenges in the field involve the development of highly specific and universally accepted senescence biomarkers and the translation of senotherapeutics from bench to bedside. Papers by Ogrodnik (Aging Cell, 2021) and Zhang et al. (Nature Reviews Drug Discovery, 2022) analyze the specificity of senescence markers and review advances in senotherapeutic strategies, including clinical trials. They are selected for addressing the current limitations and future potential of senescence-targeted interventions.

Conclusions

Cellular senescence research has indicated its dual role in supporting tissue repair and contributing to aging pathologies. Progress in identifying senescent cells and factors involved in senescence has led to the emergence of therapeutic strategies aimed at reducing the burden of senescent cells. However, challenges remain in universal biomarker discovery, understanding senescence heterogeneity, and translating senoteric therapies into clinical practice. Despite these hurdles, targeting senescence offers a promising avenue to improve health span and treat age-related diseases.