Stress, DNA damage and ageing -- an integrative approach

Area of Science:

• Gerontology
• Molecular Biology
• Genetics

Background:

• Ageing involves multiple complex mechanisms.
• Reactive oxygen species (ROS) induce endogenous stress, leading to DNA damage.
• This DNA damage is increasingly recognized as a unifying factor in ageing.

Purpose of the Study:

• To review the contributions of stress-induced DNA damage to cellular ageing.
• To explore the interconnections between different DNA damage mechanisms and ageing.
• To highlight the potential of integrative approaches and computational modeling.

Main Methods:

• Review of existing literature on DNA damage and ageing.
• Focus on nuclear DNA damage and repair via poly(ADP-ribose) polymerase-1.
• Analysis of telomeric DNA damage and cell senescence.
• Examination of mitochondrial DNA damage and mutations.

Main Results:

• Nuclear DNA damage, telomere shortening, and mitochondrial DNA mutations are key contributors to ageing.
• Poly(ADP-ribose) polymerase-1 plays a role in repairing nuclear DNA damage.
• Telomere damage drives cell senescence, a hallmark of ageing.
• Mitochondrial DNA damage and mutations accumulate with age.

Conclusions:

• Stress-induced DNA damage is a central mechanism linking various ageing pathways.
• An integrative approach, combining experimental data with computational modeling, is essential.
• This approach can help unravel the complexity of cellular ageing and identify potential interventions.