Senescence

• Senescence refers to a state where cells permanently stop dividing but remain metabolically active.
• Senescent cells accumulate in tissues with age, contributing to chronic inflammation and tissue dysfunction.
• They secrete a unique set of molecules known as the Senescence-Associated Secretory Phenotype (SASP).
• Senescence plays a significant role in biological aging and the development of various age-related pathologies.
• Targeting senescent cells is an emerging therapeutic strategy for combating age-related diseases.

What is Senescence?

Senescence refers to a cellular state of irreversible growth arrest, meaning the cells stop dividing permanently. While senescent cells are no longer able to proliferate, they remain metabolically active and undergo profound changes in gene expression and function. This process was first observed in cultured human fibroblasts that reached their replicative limit, known as the Hayflick limit.

Initially viewed primarily as a tumor-suppressive mechanism, preventing the proliferation of damaged or potentially cancerous cells, the understanding of senescence has expanded significantly. It is now recognized as a complex biological phenomenon involved in various physiological processes, including embryonic development, wound healing, and tissue repair. However, the accumulation of senescent cells with age is increasingly linked to detrimental effects on tissue function and overall health.

Cellular Senescence Explained

Cellular senescence explained involves a distinct set of characteristics that differentiate senescent cells from quiescent or terminally differentiated cells. These features include an enlarged and flattened morphology, resistance to programmed cell death (apoptosis), and significant chromatin remodeling. A hallmark of senescent cells is the Senescence-Associated Secretory Phenotype (SASP), a complex mixture of pro-inflammatory cytokines, chemokines, growth factors, and proteases that they secrete into their microenvironment.

The triggers for cellular senescence are diverse and include telomere shortening (replicative senescence), DNA damage, oncogene activation, oxidative stress, and mitochondrial dysfunction. These stressors activate specific signaling pathways that lead to cell cycle arrest, primarily through the activation of tumor suppressor proteins like p53 and p16. The persistent presence of senescent cells and their SASP can disrupt tissue homeostasis, promote chronic inflammation, and impair the regenerative capacity of surrounding tissues.

Key features of senescent cells include:

• Irreversible cell cycle arrest
• Resistance to apoptosis
• Altered gene expression and metabolism
• Secretion of the Senescence-Associated Secretory Phenotype (SASP)
• Enlarged and flattened morphology

Biological Aging and Senescence

The connection between biological aging and senescence is a rapidly evolving area of research. As organisms age, senescent cells accumulate in various tissues and organs, contributing to the decline in physiological function characteristic of aging. This accumulation is thought to be a major driver of age-related pathologies, including cardiovascular diseases, neurodegenerative disorders, metabolic syndromes, and certain cancers. For instance, the World Health Organization (WHO) projects that by 2030, one in six people globally will be aged 60 years or over, highlighting the increasing burden of age-related conditions linked to processes like senescence.

The Senescence definition biology provides a framework for understanding how these cellular changes contribute to the aging phenotype. The chronic inflammation induced by the SASP can damage healthy cells, impair stem cell function, and create a pro-tumorigenic environment. Researchers are actively exploring therapeutic strategies, such as senolytics (drugs that selectively kill senescent cells) and senomorphics (drugs that modulate the senescent phenotype), to mitigate the detrimental effects of senescent cells and potentially extend healthspan.