Senescence (Biological Aging)
Senescence is the gradual deterioration of function observed in most complex lifeforms, leading to increased mortality after maturation. It can refer to:
- Cellular senescence – aging at the cell level
- Organismal senescence – aging of the whole organism
The study of biological aging is called biogerontology.
Key points about senescence:
- Not all organisms experience senescence; some may even show a decrease in mortality with age.
- Accelerated aging diseases are rare in humans, and extremely rare conditions, like "Syndrome X," result in lifelong childhood-like characteristics.
- Environmental factors, such as UV radiation, can accelerate aging in specific tissues.
- Biological aging may occur at different rates in different individuals of the same species.
Hypotheses for senescence:
- Programmed changes in gene expression
- Accumulation of damage from biological processes
Cellular Senescence
- Definition: Diploid cells stop dividing after a limited number of divisions.
- Replicative senescence: Caused by telomere shortening, triggering a DNA damage response.
- Can also result from:
- DNA damage from ROS
- Activation of oncogenes
- Cell-cell fusion
Features of senescent cells:
- Metabolically active but non-dividing
- Flattened morphology
- Pro-inflammatory secretory phenotype
- Positive senescence-associated β-galactosidase staining
Functions of senescent cells:
- Tumor suppression
- Wound healing
- Embryonic/placental development
Pathological role:
- Contribute to age-related diseases
- Elimination of senescent cells in mice increases resistance to aging-associated diseases
Evolutionary role:
- Prevents cancer by halting replication of damaged somatic cells
- Telomere shortening limits the number of cell divisions, contributing to aging
Exceptions:
- Some cells are biologically immortal, e.g., certain stem cells, lobsters, and some plants.
Telomere effects:
- Shortening activates senescence toxins (e.g., progerin)
- Telomerase reactivation in cancer cells enables immortality but increases cancer risk