Preliminary Evidence for Increased Histone Succinylation as a Potential Epigenetic Marker for Longevity

Area of Science:

• Epigenetics and Aging Research
• Biochemistry of Histone Modifications

Background:

• Histone post-translational modifications (PTMs) regulate gene expression and are crucial for development, metabolism, and aging.
• While methylation and acetylation are well-studied, histone succinylation's role, particularly in aging and longevity, is largely unknown.

Purpose of the Study:

• To investigate the role of histone succinylation in aging and exceptional longevity.
• To explore the impact of succinate availability on healthspan and physical performance during aging.

Main Methods:

• Mass spectrometry-based proteomics to quantify histone succinylation in human B-cells from different age and longevity groups.
• Nuclear proteomics to analyze succinylated protein enrichment.
• Supplementation with succinic acid in middle-aged mice to assess healthspan impacts.

Main Results:

• Histone succinylation was significantly higher in offspring of long-lived individuals (OPEL) compared to young and older individuals without parental longevity (OPUS).
• Succinylated proteins were enriched in OPEL samples, suggesting a role in chromatin organization.
• Succinic acid supplementation in mice did not affect body weight, frailty, or cognition but improved motor coordination and muscle strength.

Conclusions:

• Enhanced histone succinylation may be a protective epigenetic mechanism associated with exceptional longevity.
• Succinate supplementation shows potential for selectively improving physical performance during aging.