Cellular Death

Cellular Aging

Cellular aging refers to the gradual decline in the functionality, replication ability, and overall health of cells over time.

It is a key component of the broader aging process in organisms and is influenced by a variety of biological, environmental, and genetic factors.

Several mechanisms drive cellular aging:

1. Telomere Shortening

Telomeres are protective caps at the ends of chromosomes that shorten with each cell division.
Once telomeres become too short, cells enter a state called replicative senescence, where they stop dividing.

2. Accumulation of DNA Damage

Cells constantly face damage to their DNA due to internal factors (e.g., reactive oxygen species) and external factors (e.g., UV radiation, toxins).
Over time, the cell's repair mechanisms become less efficient, leading to genomic instability.

3. Oxidative Stress

Reactive oxygen species (ROS), byproducts of normal cellular metabolism, can damage DNA, proteins, and lipids.
Accumulated oxidative damage contributes to the deterioration of cellular function.

4. Epigenetic Changes

Alterations in the chemical modifications of DNA and histones (e.g., methylation, acetylation) can change gene expression patterns.
These changes may silence genes required for cellular repair or activate genes that promote aging.

5. Protein Misfolding and Aggregation

Aging cells often lose efficiency in properly folding proteins and clearing misfolded proteins.
This can lead to the accumulation of toxic protein aggregates, as seen in conditions like Alzheimer’s disease.

6. Mitochondrial Dysfunction

Mitochondria, the powerhouses of the cell, decline in function with age.
Reduced energy production and increased production of ROS from dysfunctional mitochondria contribute to cellular aging.

7. Senescence and the Senescence-Associated Secretory Phenotype (SASP)

Senescent cells secrete inflammatory cytokines, growth factors, and proteases, collectively known as SASP.
This can affect neighboring cells and tissues, promoting inflammation and age-related diseases.

8. Loss of Proteostasis

Aging cells are less efficient at maintaining the balance of protein synthesis, folding, and degradation.
Dysfunctional proteostasis contributes to cellular stress and functional decline.

Implications of Cellular Aging

Cellular aging underlies many age-related diseases, such as cardiovascular disease, diabetes, neurodegenerative disorders, and cancer.

Understanding the mechanisms of cellular aging can help in developing therapies to slow down the aging process, repair damaged cells, or replace aging cells with younger ones, as seen in regenerative medicine.