Ageing - Oxidative stress, PTMs and disease

Area of Science:

• Biochemistry
• Gerontology
• Molecular Biology

Background:

• Post-translational modifications (PTMs) link oxidative stress, inflammation, and aging.
• PTMs like phosphorylation, acetylation, and ubiquitination are crucial in healthy aging and age-related diseases (neurodegeneration, cancer, etc.).
• Evidence from progeroid syndromes and long-lived species highlights PTMs' regulatory role in aging.

Purpose of the Study:

• To explore the role of PTMs in aging processes and age-related diseases.
• To investigate PTM-based therapeutics as potential treatments for age-related conditions.
• To highlight the potential of targeting epigenetic pathways modulated by PTMs.

Main Methods:

• Review of existing literature on PTMs, aging, and age-related diseases.
• Analysis of PTM involvement in epigenetic and non-epigenetic aging pathways.
• Examination of FDA-approved inhibitors and senolytic compounds (e.g., dasatinib, quercetin) as PTM-targeting agents.

Main Results:

• PTMs are implicated in major hallmarks of aging and various age-related diseases.
• Epigenetic histone modifications, influenced by PTMs, significantly impact aging and lifespan.
• Existing drugs targeting PTMs (e.g., kinase inhibitors) show potential for anti-aging effects and treating senescence.

Conclusions:

• PTM-based therapeutics represent a promising avenue for reducing the burden of age-related diseases.
• Further research is needed to identify optimal PTM-based candidates for treating the 'diseasome of aging'.
• Investigating beneficial effects and side-effects of PTM inhibitors is crucial for therapeutic development.