Thanks to the ageing process, both men and women use hair dye, exercise to reduce flabbiness, undergo Botox injections to hide wrinkles and go for rejuvenation to plastic surgeons.
Although all humans share similar changes during aging such as gray hair, wrinkles and a general decline in function, aging is considered to be the result of a cellular wear-and-tear process due to accumulated random damage, such as genetic mutations or DNA structural damage.
Now, researchers at Bar-Ilan University (BIU) in Ramat Gan (near Tel Aviv) have developed a novel computational method that quantifies – for the first time – the coordination level among different genes. It reveals a new hallmark of aging that could require a change of course in current efforts to develop healthy-aging treatments. There study has just been published in the prestigious journal Nature Metabolism under the title “Age-related loss of gene-to-gene transcriptional coordination among single cells.”
How is it that random, disorganized damage that accumulates in different amounts among different humans, and among different cells of the same individual eventually leads to the same outcomes? Several theories try to address this paradox, and they have great implications for our ability to affect the aging process, making elderly life better and longer. The potential to develop treatments for aging depends on understanding the fundamental process of growing old.
A common approach holds that most cells in the human body are barely damaged during aging, while just a few “rotten apples” – a small fraction of non-functioning cells – are significantly damaged. Accordingly, a potential treatment for aging could involve removing these few highly-damaged cells.
Approximately 15 years ago Prof. Jan Vijg, the Holland-born chairman of molecular genetics at the genetics department at Albert Einstein College of Medicine in New York, proposed a different approach. He suggested that the proper function of biological tissues may decline during aging because many cells lose their ability to tightly regulate their genes. According to Vijg’s theory, on the one hand there are no single non-functioning cells on the one hand, but on the other hand, none of the “rotten apples” is “fresh.” Evidence for Vijg’s theory has never been fully presented, until now.
In the Bar-Ilan study, the researchers report, for the first time, evidence that supports Vijg’s theory. Using a novel approach from physics, they developed a computational method that quantifies the coordination level between different genes. With this approach, they measured the gene activity of individual cells and compared cells from old and young subjects, discovering phenomena never before observed: old cells lost significant coordination levels compared to young cells.
To test the consistency of this phenomenon, they analyzed data collected from more than 20 experiments from six different labs around the world. In all cases, they found reduced levels of coordination during aging among different organisms: human, mice and fruit flies and among different cell types: brain cells, hematopoietic stem cells that give rise to other blood cells, pancreatic cells and more.
“In biology, it is very difficult to achieve consistent results for different types of cells, tissues, experiments and organisms due to the high sensitivity of equipment and experimental setup,” noted Dr. Orr Levy from the group of the study’s lead author, Dr. Amir Bashan, of BIU’s physics department.
“Our method found the same pattern in more than 20 datasets. Finding evidence for coordination of genes was amazing, but even more outstanding was finding that this property of coordination dramatically declines with age,” added Guy Amit from Bashan’s team. Bashan and team collaborated on the research with Prof. Haim Cohen and Prof. Sol Efroni from BIU and Prof. Yang-Yu Liu and Prof. Peter Castadli from Harvard Medical School.
The researchers also observed coordination reduction in tissues with an increased level of damage, suggesting a direct link between increased damage level and coordination breakdown. The findings support the theory that during aging, accumulated random damage affects regulation mechanisms and disrupts the ability of genes to coordinate (resulting in a general decrease in tissue function), just like an orchestra without proper coordination between musicians ruins a symphony.
This study conclusively demonstrates the long-speculated relationship between aging, gene regulation and somatic damage. The results open up new avenues of research with practical implications. If the same level of coordination reduction among genes is indeed a leading cause for aging phenomena, there may be a need to change course in current efforts to develop aging treatments.