Children of parents with alcohol use disorders are at increased risk for premature aging and related health problems, a recent study from the Texas A&M School of Veterinary Medicine and Biomedical Sciences found. The research shows that parents who abuse alcohol can pass on symptoms of premature aging to their offspring, such as high cholesterol, heart problems, arthritis and early-onset dementia that can manifest in their children’s 40s. The findings were published in the journal Ageing and disease.
The study, led by Michael Golding, professor in the Department of Veterinary Physiology and Pharmacology at VMBS, aimed to investigate the causes of early aging and susceptibility to disease in children of alcoholic parents. Scientists had long observed that children from these backgrounds were more susceptible to disease and behavioral problems, but the underlying reasons remained unclear.
Golding and his team discovered that dysfunction of mitochondria, the energy-producing structures in cells, was a key factor. This mitochondrial dysfunction, inherited from parents with alcohol abuse disorders, leads to early signs of age-related diseases in offspring. The study’s findings highlight the importance of mitochondrial health and suggest that improving it through exercise and increased intake of certain vitamins could potentially delay these inherited dysfunctions.
The researchers used a mouse model to simulate the effects of parental alcohol consumption on offspring. Male and female mice were exposed to either a control treatment (water) or a 10% ethanol solution to simulate alcohol consumption. Exposure began when the mice reached adulthood and continued for several weeks. The females were exposed to alcohol both before conception and during the early stages of pregnancy.
The researchers then compared offspring from different groups: control group (no alcohol consumption), maternal group (only the mothers drank alcohol), paternal group (only the fathers drank alcohol) and double group (both parents drank alcohol).
Males were exposed to alcohol for six weeks, corresponding to a complete spermatogenesis cycle, to ensure that possible epigenetic changes would be present in their sperm at mating. Females were exposed to alcohol starting ten days before mating and until day ten of pregnancy, after which all treatments were stopped.
The offspring were then monitored for various aging markers and mitochondrial functions at different stages of their lives. A detailed analysis was performed at 300 days of age (which corresponds to the median age in mice).
The researchers discovered evidence that parental alcohol consumption leads to premature aging and mitochondrial dysfunction in their offspring. One of the most striking discoveries was the increase in cellular senescence in the brains and livers of the offspring. Cellular senescence is a condition in which cells stop dividing and accumulate damage, contributing to aging and age-related diseases. The study found increased levels of senescence-related β-galactosidase activity and increased expression of genes such as p21 and p16Ink4a in the brains of the offspring, suggesting accelerated aging.
“Senescence is an important marker of age, especially in the brain, where it leads to cognitive impairment and memory problems,” Golding said. “Scientists have long known that heavy alcohol consumption in adults can lead to premature senescence.”
In the liver, the male offspring showed significant markers of early liver disease, such as increased fat accumulation and fibrosis. These effects were most pronounced in the offspring from the dual exposure group, in which both parents had consumed alcohol, suggesting an additive effect of maternal and paternal alcohol consumption. In addition, the offspring had higher levels of inflammatory markers and signs of liver damage, such as increased alanine and aspartate transaminase levels, despite never having consumed alcohol themselves.
“We also see an increase in fat in the liver, which forms scar tissue,” Golding said. “This is particularly common in male offspring. If both parents have an alcohol problem, this can have an even greater impact on the male offspring, making them even more susceptible to liver disease.”
In addition, the study highlighted mitochondrial dysfunction as a key factor in the early aging process observed in these offspring. Mitochondrial health was assessed by examining the ratio of long to short isoforms of OPA1, a protein involved in mitochondrial dynamics. The offspring of alcohol-exposed parents, particularly those from the dual-exposure group, showed a shift toward the short isoform of OPA1, indicating mitochondrial stress. This mitochondrial dysfunction was accompanied by a decrease in the NAD+/NADH ratio and reduced levels of the proteins SIRT1 and SIRT3, which are essential for maintaining mitochondrial function and preventing oxidative stress.
“Now we know that they inherit dysfunction of their mitochondria due to their parents’ drug abuse,” Golding said. “The dysfunction causes these individuals to show early signs of age-related diseases at a young age.”
The study’s findings suggest that parental alcohol consumption can have long-term and harmful effects on the health and aging of their offspring. The results underscore the importance of considering both maternal and paternal health before conception.
“Preconception parental health – the overall health of both parents before pregnancy – is critical to the health of the offspring,” he explained. “The more you can do as future parents to develop a healthy mindset and lifestyle, the greater impact you will have on your child’s health, both right at birth and into their 20s and 40s.”
Authors of the study “Parental Alcohol Exposures Associate with Lasting Mitochondrial Dysfunction and Accelerated Aging in a Mouse Model” are Alison Basel, Sanat S. Bhadsavle, Katherine Z. Scaturro, Grace K. Parkey, Matthew N. Gaytan, Jai J. Patel, Kara N. Thomas and Michael C. Golding.
