Volume 8 Issue 9, September 2007

Mutations in genes that regulate endocrine signalling pathways can increase the lifespans of worms, flies and mammals. Endocrine pathways might therefore serve as targets for the manipulation of the ageing process and prevention of age-related diseases.

Changes in nuclear architecture are a hallmark of ageing in yeast and mammals. These changes seem to be driven by DNA damage, which results in age-related alterations in gene expression, and may be a conserved cause of ageing.

Evidence from rodent and human experimental studies supports the view that a decline in the regenerative function of stem cells with age contributes to mammalian ageing and, possibly, several age-associated diseases. However, a few crucial questions remain to be resolved.

Convergent mechanisms limit the amount of cellular damage and thereby protect against both cancer and ageing, whereas divergent mechanisms prevent excessive proliferation and, therefore, prevent cancer but promote ageing. The net balance between these mechanisms ensures a healthy, cancer-free lifespan until late adulthood in most individuals.

According to the free-radical theory, oxidizing species — including hydrogen peroxide (H₂O₂) — are generated during aerobic respiration and cause molecular damage and ageing. However, recent evidence suggests that H₂O₂that is produced as a signalling molecule by a selected genetic programme regulates ageing.

Various stress signals can induce a state of irreversible cell-cycle arrest that is known as cellular senescence. Understanding the causes of cellular senescence has provided insight into some of its consequences: it is important for suppressing cancer and possibly contributes to ageing.

The relationship between autophagy and apoptosis is complex; autophagy constitutes an adaptive stress response that avoids cell death and suppresses apoptosis under certain circumstances, whereas in other cellular settings it contributes to the demise of cells through an alternative cell-death pathway.