13-Year Study Proves for the First Time: Loss of Epigenetic Information Causes Aging, and Aging Signs May Be Reversible

A 13-year international study has shown for the first time that the deterioration of how DNA is organized and regulated (known as epigenetics) can drive an organism’s aging, independent of changes to the genetic code itself.

The study showed that the loss of epigenetic information (nucleic acid sequence) causes mice to age, and that restoring its integrity can reverse signs of aging. Even more, by manipulating the epigenome, researchers found they could drive the aging process forward or backward.

The results were published on January 12 in the journal Cell under the title “Loss of epigenetic information as a cause of mammalian aging.”

The paper’s senior author, David Sinclair, professor of genetics at the Blavatnik Institute at Harvard Medical School and co-director of the Paul F. Glenn Center for Biology of Aging Research, said: “We believe this study is the first to show that changes in epigenetic information are a primary cause of mammalian aging.”

Epigenetic molecules act as switches for gene activity, determining cell type and function, such as nerve cells or muscle cells. This differentiation occurs because, although every cell in an organism has the same DNA, the switches for specific genes can be controlled. Epigenetics is like a cell’s operating system, allowing cells to use the same genetic material in different ways.

The team tested whether aging is a result of this process by accelerating the number of breaks in laboratory mice. At first, epigenetic factors temporarily paused their gene-regulation duties to coordinate DNA repair, but the researchers found they became “distracted” and did not return to their original work after repairing the damage. This caused the epigenome to become disorganized and lose its original information, leading chromatin to condense and unwind in the wrong patterns—a hallmark of epigenetic dysfunction. The mice showing aging responses confirmed this.

The team’s extensive series of experiments proved that DNA changes are not the only or primary cause of aging. Instead, the findings suggest that chemical and structural changes to chromatin (the complex of DNA and protein that forms chromosomes) promote aging without changing the genetic code itself.

Next, the researchers gave the mice a cocktail gene therapy that reversed the epigenetic changes they had induced. The mice’s organs and tissues ultimately returned to a youthful state.

Jae-Hyun Yang, co-first author of the paper, said: “We expect these results to be seen as a turning point in our ability to control aging. These findings will change how we view the aging process and how we approach aging-related diseases.”

Original article: “Loss of Epigenetic Information Can Drive Aging, Restoration Can Reverse It”