What causes our body to age? Four complementary studies, including one from Northwestern Medicine, reached the same conclusion: long genes. In a new article, scientists describe their findings and how they advance existing knowledge about aging.

“Long genes that become less active as we age may be an important cause of aging in our bodies,” said corresponding author Thomas Stoger, professor of pulmonary and critical care at Northwestern University Feinberg School of Medicine and member of the Potocsnak Longevity Institute. . “Our discovery advances the field by identifying a single phenomenon that unifies much of the current knowledge about aging and makes this fundamental phenomenon measurable.”

Gene length and biological aging

The article highlights the joint findings of four international research groups. Trends in Genetics 21 March. The groups were the first to conclude that most aspects of biological aging are related to gene length.

Conditions known to accelerate aging reduce the activity of long genes. This includes smoking, alcohol, oxidative stress and UV exposure. Conditions known to slow aging increase the activity of tall genes, such as calorie restriction. Additionally, genes that are too short or too long encode cellular processes known to change with aging, such as cellular energy production, protein synthesis, and neuronal signaling.

Link between tall genes and aging

“Gene regulation is one of the most important processes in life, and our four studies explain why the activity of long genes changes, especially with aging,” Stoeger said. said. “We have shown that the same situation occurs in patients with Alzheimer’s, an age-related disease as well as aging. Our findings help us rethink the causes of neurodegenerative diseases such as Alzheimer’s disease. Because genes with neural functions are extremely long, the reduced activity of cells with long genes prevents neural function from functioning properly.” “We assume it cannot produce enough biomaterial to support it.”

According to the scientists’ report, the trigger of aging is not the specific genes involved or the function of these genes, but a physical phenomenon related to the length of the genes. Initial findings were based on a mixture of molecular data from humans, mice, rats, marine fish, C. elegans, D. melanogaster and mouse experiments. Previously, scientific research tried to identify specific genes responsible for aging. This new view differs from existing biological approaches that examine the influence of individual genes.

DNA damage and aging

Long genes have more potential areas that can be damaged. Scientists compare this to a journey; The longer the trip, the more likely it is that something will go wrong. Because the physiological role of some cell types depends on genes that are longer than other cell types, some cell types are more likely to be damaged by DNA damage that accumulates with age. During aging, genes become damaged as the DNA strands containing the genes break. This prevents cells from reading and activating the information contained in the gene. The longer the gene, the more likely it is that at least one site of DNA damage will be present and the gene will be stopped from being activated.

Nerve cells are particularly susceptible to this condition because they are known to depend on long genes and divide slowly or not at all. Many of the genes linked to brain loss during aging and Alzheimer’s disease are extremely long. Childhood cancer patients treated with DNA-damaging chemotherapy subsequently suffer from premature aging, including neurodegeneration.