The aging process in the general population is influenced by various factors, including lifestyle and diet. Certain macro- and micronutrients in our diet interact directly with the human genome, impacting systems such as the immune system. Fanconi anemia (FA), a rare genetic disease, also illustrates the influence of diet on the severity of clinical features. Researchers have explored the connection between these aspects to gain insights into cellular aging.
“We use Fanconi anemia as a prime example of premature aging to illustrate that aging results from an imbalance in our genome—specifically, an imbalance between cellular repair mechanisms and the accumulation of molecular damage,” emphasize Dr. Eunike Velleuer and Prof. Carsten Carlberg, authors of a publication in the journal Nutrients.
What is Fanconi Anemia?
Fanconi anemia (FA) is a rare genetic disorder occurring in approximately one in 300,000 people. It is primarily caused by mutations in 22 different genes responsible for repairing damaged DNA. Individuals with FA often have congenital defects and a high risk of cancers, particularly squamous cell carcinoma of the oral cavity. Due to defects in the DNA repair process, conventional cancer treatments like chemotherapy are ineffective.
A Nutrigenomic Perspective
Aging, unlike FA, is not a disease but a natural process involving the accumulation of molecular and cellular damage, leading to deteriorated function in cells, tissues, and organs. Both the general population and FA patients experience varying rates of aging. While genetics play a role in longevity, lifestyle choices such as diet, smoking, physical inactivity, and environmental factors are significant determinants.
“Nutrition does more than provide essential macro- and micronutrients. Certain food molecules ‘communicate’ with our genome and epigenome (chemical modifications to DNA that regulate its function), thereby modulating gene expression in the immune system,” explains Prof. Carsten Carlberg, who leads the Nutrigenomics Team at the Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences.
Fanconi Anemia and Aging
The lifestyle of FA patients, including diet and physical activity, can influence the onset and severity of clinical features. Thus, FA serves as a model for understanding the aging process in the general population. Researchers have demonstrated that non-genetic factors involve cellular disturbances that modulate signal transduction pathways, affecting the epigenome by regulating chromatin-modifying enzymes.
In essence, the balance of genetic and environmental risk factors impacts both cancer onset and aging rates, linked to the transduction of dietary molecule signals. Changes in the epigenome correlate with chronological age and age-related diseases such as cancer. Some individuals may exhibit a ‘younger’ epigenome in their tissues compared to their chronological age, while others may have an ‘older’ epigenome, correlating with earlier onset of age-related diseases—a pattern observed in premature aging diseases. Conversely, offspring of ‘super-aged’ individuals often show a lower epigenetic age in their blood compared to age-matched controls, making epigenetic signatures valuable biomarkers of aging.
“The results of our research benefit not only people with FA but also the general population. By monitoring the aging process at a molecular level, we can develop personalized nutritional or preventive recommendations. Additionally, these epigenetic signatures, being protein-based, could potentially form the basis for drugs that delay or even reverse age-related diseases such as cancer,” the researchers conclude.
