Four concurrent studies to find the reason behind the aging process in humans including one conducted by Northwestern Medicine have all concluded that it is due to long genes.
In a recent study, the researchers outline their findings and their significance in adding to the current knowledge on the process of aging.
"Long genes that become less active with age may be the central cause of ageing in our bodies," said co-corresponding author Thomas Stoeger, assistant professor of medicine in pulmonary and critical care at Northwestern University Feinberg School of Medicine and a member of the Potocsnak Longevity Institute. "Our finding advances the field by identifying a single phenomenon that connects most existing knowledge about ageing and makes this underlying phenomenon measurable."
The findings of four international research groups, which were published in Trends in Genetics on March 21, were featured in a paper. These groups are the first to determine that gene length is closely associated with various aspects of biological aging.
Certain factors that are recognized to speed up the aging process reduce the functioning of lengthy genes. These factors include oxidative stress and exposure to UV radiation. On the other hand, conditions that are known to slow down aging enhance the activity of lengthy genes, such as caloric restriction. Additionally, genes that are either very short or very long are responsible for cellular processes that are known to undergo changes during aging, such as the generation of cellular energy, protein synthesis, and the transmission of neural signals.
"The regulation of genes is one of the most central processes of life, and our four studies explain why the activity of long genes in particular change in ageing," Stoeger said. "In addition to ageing, we show that the same finding occurs in patients with Alzheimer's disease, an age-associated disease. Our findings help us rethink the causes of neurodegenerative diseases such as Alzheimer's disease. Because genes with neural function are unusually long, we hypothesize that the decreased activity of long gene cells fails to produce sufficient biomaterials to properly maintain neural function."
According to scientists, the cause of aging is a physical process linked to the size of genes rather than the specific genes themselves or their functions. These conclusions were drawn from a combination of molecular data gathered from various species, including humans, mice, rats, killifish, C. elegans, and D. melanogaster, as well as experiments conducted on mice. In the past, scientific studies aimed to pinpoint individual genes that contribute to aging. However, this fresh perspective departs from previous biological approaches that focused on examining the impact of single genes.
Longer genes have a higher potential for damage, according to scientists who compare it to a road trip. Just like a longer trip increases the likelihood of something going wrong, longer genes are more susceptible to DNA damage. This is particularly significant because certain cell types rely on longer genes for their physiological functions, making them more prone to DNA damage as they age. As genes break during the aging process, cells are unable to read and activate the information contained within them. The length of a gene directly correlates to the probability of having at least one site of DNA damage, which ultimately hinders the gene's activation.
Neural cells, which depend on lengthy genes and have a slow or non-dividing nature, are highly vulnerable to this phenomenon. Numerous genes linked to brain deterioration during aging and Alzheimer's disease are notably long. Pediatric cancer patients, who are treated with DNA-damaging chemotherapy and cured, experience premature aging and neurodegeneration later in life.
