Defining Cellular Senescence
Senescence is a fundamental biological process where a cell permanently loses its ability to divide, but unlike apoptosis (programmed cell death), it remains metabolically active. This state of irreversible growth arrest is a natural part of an organism's life cycle and serves various physiological roles, though its accumulation is linked to aging.
Key Characteristics and Triggers
Senescent cells exhibit several distinct characteristics, including altered gene expression, resistance to apoptosis, and a prominent 'senescence-associated secretory phenotype' (SASP), where they secrete pro-inflammatory cytokines, chemokines, growth factors, and proteases. Common triggers for senescence include telomere shortening, DNA damage, oncogenic stress, and oxidative stress, acting as a crucial safeguard against uncontrolled cell proliferation like cancer.
The Role of Senescence in Health and Disease
While acting as a tumor-suppressive mechanism by halting the proliferation of damaged or abnormal cells, the accumulation of senescent cells over time contributes significantly to aging and age-related diseases. Their persistent pro-inflammatory secretions (SASP) can disrupt tissue homeostasis, leading to conditions such as fibrosis, arthritis, cardiovascular disease, and neurodegeneration.
Distinction from Organismal Aging and Importance
It's important to distinguish cellular senescence from organismal aging; senescence is a cellular-level process, while aging is the complex decline of an entire organism. Understanding senescence is vital for developing therapies aimed at improving healthspan and treating age-related pathologies, by either selectively removing senescent cells (senolytics) or inhibiting their pro-inflammatory activities (senomorphics).