Parental Alcohol Exposures Associate with Lasting Mitochondrial Dysfunction and Accelerated Aging in a Mouse Model

Area of Science:

• Neuroscience
• Toxicology
• Gerontology

Background:

• Fetal alcohol exposure causes mitochondrial dysfunction.
• Long-term effects of this dysfunction into adulthood and links to accelerated aging in FASDs are unknown.

Purpose of the Study:

• Investigate if parental alcohol exposure induces premature cellular senescence and accelerated aging in adult offspring.
• Examine the impact of maternal, paternal, and dual-parental alcohol exposure on age-related outcomes.

Main Methods:

• Utilized a multiplex preclinical mouse model.
• Assessed markers of cellular senescence and age-related outcomes in adult offspring (postnatal day 300).
• Analyzed mitochondrial function, NAD+/NADH ratio, and SIRT1/SIRT3 expression.

Main Results:

• Adult offspring of alcohol-exposed parents showed increased cellular senescence markers in the brain and liver.
• Dual-parental alcohol exposure in males exacerbated age-related liver disease indicators more than single-parent exposure.
• Chronic parental alcohol use resulted in enduring mitochondrial dysfunction, reduced NAD+/NADH ratio, and altered SIRT1/SIRT3 expression.

Conclusions:

• Parental alcohol use can program offspring for accelerated aging via mitochondrial dysfunction.
• This accelerated aging may contribute to certain aspects of fetal alcohol spectrum disorders (FASDs).
• Enduring changes in mitochondrial bioenergetics and NAD+ metabolism are implicated.