Rewriting the Rules of Aging: New Chromatin Discovery Challenges Conventional Wisdom
The research could contribute to the development of more effective anti-aging treatments in the future.
The body’s aging process may be more resilient than previously thought, according to a new study.
Published in the Journal of the American Chemical Society, the research by scientists at King’s College London and their collaborators suggests that chromatin—the complex of DNA and proteins that houses each cell’s genome—is more resistant to aging than previously believed. This discovery may help explain how the body withstands the inevitable “wear and tear” of aging while also highlighting areas where it may be more vulnerable. These insights could pave the way for future anti-aging treatments throughout the body.
Dr Luis Guerra explains: “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.”
Proteins, much like the rest of the body, change when aging. This is especially the case for the histone proteins that make up chromatin, which may “live” for ~100 days before being replenished and replaced. During their lifetime, proteins are stretched and distorted, or experience processes that are similar to rusting. This damage results in naturally occurring chemical changes to the protein called post-translational modifications, or PTMs.
Building and Testing Artificially Aged Chromatin
By changing the physical and chemical structures of a protein, these processes can alter its function and even cause it to fail. In some cases, this failure can lead to diseases like cancer but the mechanisms of just how this occurs is often unclear. Furthermore, because natural aging is slow, studying this process within proteins in the body can be difficult.
To uncover the foundations of how proteins experience ‘wear-and-tear’ as they age, the team chemically built chromatin in a test tube at two distinct stages in its lifecycle – recently formed and very old, with the latter containing a PTM associated with aging. At approximately three million daltons, a unit of mass for atomic-scale objects like atoms, the team believes these chromatin models with controlled aging “scars” are the largest of their kind.
They found that the aging process had very disparate effects. Despite extreme local changes to the protein brought by aging-related PTMs, the overall structure and integrity of chromatin seemed unaffected. However, enzymes that typically interact with it could no longer recognize these aged regions as chromatin and failed to function.
Implications for Future Anti-Aging Treatments
Dr Luis Guerra explains: “This suggests that chromatin, which sets out the structure of DNA, is more robust than we thought… 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.”
“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.”
“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 building aged biomolecules like proteins and working to identify the ‘tipping point’ of when wear-and-tear irreparably impedes the function of chromatin and other complex cellular components, the team hopes to empower future generations of pharmacists to make more effective anti-aging treatments.
Reference: “Semisynthesis of Isomerized Histone H4 Reveals Robustness and Vulnerability of Chromatin toward Molecular Aging” by Tianze Zhang, Luis F. Guerra, Yana Berlina, Jon R. Wilson, Beat Fierz and Manuel M. Müller, 2 February 2025, Journal of the American Chemical Society.