Exploring Chromatin's Resilience to Develop Anti-Aging Strategies

The process of aging in the body may be more resilient than previously believed, according to a new study.

The research, published in the Journal of the American Chemical Society by scientists at King’s College London and their collaborators, indicates that chromatin, the combination of DNA and proteins that house the genome in each cell, is more resistant to aging than previously assumed.

This discovery could help explain how the body manages the inevitable “wear-and-tear” of aging and identify areas where it is more vulnerable, potentially paving the way for future anti-aging therapies across the body.

Proteins, like other parts of the body, change as they age. This is particularly true for histone proteins, which are key components of chromatin and typically “live” for about 100 days before being replaced.

Over time, proteins are subjected to stretching, distortion, or processes akin to rusting. These changes result in naturally occurring chemical alterations known as post-translational modifications (PTMs).

These processes, which alter the physical and chemical structure of proteins, can impact their function and, in some cases, cause them to fail. Such failures may lead to diseases like cancer, though the exact mechanisms behind this are often unclear. Additionally, because natural aging occurs gradually, studying these processes in proteins within the body is challenging.

To investigate how proteins experience “wear-and-tear” as they age, the researchers chemically recreated chromatin in a test tube at two distinct stages of its lifecycle: newly formed and aged, with the latter containing a PTM linked to aging.

Weighing approximately three million daltons, a unit of mass for atomic-scale objects, the researchers believe these chromatin models with controlled aging “scars” are the largest of their kind.

The study revealed that the effects of aging were highly variable. While aging-related PTMs caused significant local changes to the proteins, the overall structure and integrity of chromatin remained intact. However, enzymes that typically interact with chromatin were unable to recognize these aged regions and failed to function properly.

This was a huge surprise for us. Experiment after experiment showed that chromatin was tolerating quite well the presence of this ‘wear-and-tear.’ But when we zoomed in and investigated biochemical processes that directly targeted these aged areas that we introduced, we saw massive effects.”

Dr. Luis Guerra, Department of Chemistry, King’s College London

Guerra said, “This suggests that chromatin, which sets out the structure of DNA, is more robust than we thought. Think of an old computer, while it may not have the latest graphics card or processor this modular piece of kit can still surf the web. It might even have a completely fried sound card, but at its core, it still functions as a computer. This could mean that the functional integrity of certain parts of the body can be maintained until those faulty parts can be repaired or switched out.”

By chemically recreating aged biomolecules like proteins and identifying the “tipping point” at which wear-and-tear irreparably disrupts the function of chromatin and other complex cellular components, the researchers aim to equip future generations of pharmacists with the tools to develop more effective anti-aging treatments.