[Molecular bases of cellular senescence: Hayflick phenomenon 50 years later]

Area of Science:

• Gerontology
• Molecular Biology
• Cell Biology

Background:

• Normal human somatic cells have finite proliferative potential, entering senescence due to DNA damage.
• Oxidative stress, exacerbated by mitochondrial dysfunction, is a primary driver of DNA damage leading to senescence.
• Accumulation of senescent cells in tissues is associated with aging and age-related pathologies, including cancer.

Purpose of the Study:

• To review the molecular determinants of cellular senescence.
• To emphasize the role of oxidative stress in senescence.
• To discuss cell cycle effectors, senescence markers, and the impact of senescent cells on age-related diseases.

Main Methods:

• Literature review and synthesis of current knowledge on cellular senescence.
• Focus on molecular mechanisms, particularly oxidative stress and mitochondrial function.
• Analysis of cell cycle regulation, senescence markers, and disease associations.

Main Results:

• Cellular senescence is a complex process initiated by DNA damage, with oxidative stress playing a critical role.
• Mitochondrial dysfunction significantly contributes to the accumulation of oxidative stress and subsequent senescence.
• Senescent cells influence the development of various age-related diseases.

Conclusions:

• Cellular senescence is a key factor in organismal aging and disease development.
• Understanding the molecular underpinnings of senescence, especially the role of oxidative stress, is crucial for addressing age-related conditions.
• Further research into senescence mechanisms may offer therapeutic targets for age-related pathologies.