Sulfur-based redox alterations in long-lived Snell dwarf mice

Area of Science:

• Metabolomics
• Aging Research
• Biochemistry

Background:

• Sulfur-based metabolites play crucial roles in cellular redox balance and aging.
• Long-lived Snell dwarf mice serve as a model to study aging-related metabolic alterations.

Purpose of the Study:

• To comprehensively map systemic differences in sulfur metabolism between Snell dwarf mice and controls.
• To investigate the impact of altered sulfur metabolism on DNA methylation and redox potential in aging.

Main Methods:

• Comparative analysis of sulfur-based redox metabolite profiles in multiple tissues.
• Measurement of enzyme activities, including cystathionine β-synthase (CBS) and methionine adenosyltransferase (MAT).
• Application of a mathematical model to elucidate methionine metabolism pathways.

Main Results:

• Snell dwarfs exhibited increased plasma methionine, hypotaurine, and taurine, with decreased cystine and glutathione, suggesting an oxidative shift.
• Elevated CBS activity in female Snell mice and increased MAT in liver correlated with higher S-adenosylmethionine and global DNA methylation.
• Mathematical modeling indicated decreased methionine transport, increased MAT, and enhanced methyltransferase activity in Snell dwarfs.

Conclusions:

• Snell dwarfism significantly alters sulfur-based redox metabolite profiles and methionine metabolism.
• These metabolic perturbations are linked to changes in DNA methylation and redox potential, offering insights into aging.
• The study provides a foundational map for understanding nutrition-linked metabolic status in long-lived models.