Biological Age

A study published in Nature Genetics and led by scientists at Van Andel Research Institute (VARI) and Cedars Sinai, have developed a new computational, straightforward method to measure cellular age. The findings may lead to simpler, better screening and a way to measure the success of anti-aging therapies.

The findings reveal a measurable, progressive loss of specific chemical tags that regulate gene activity and can be detected at the earliest stays of development. These changes will continue throughout a person’s life and will correlate with cellular rather than chronological age.

The study builds on a 2011 long time collaboration and discovery by Benjamin Berman, Ph. D. of Cedars-Sinai and Peter Laird, Ph.D. and Hui Shen, Ph.D. of VARI. The 2011 discovery first determined loss of these DNA marks (called methyl groups) occurs in specific areas of the genome. However, at the time the techniques used could not detect this process occurring in normal cells. Our cellular clock begins ticking the moment our cells start dividing. This method allowed the researchers to track the history of the past divisions and measure age-related changes to the genetic code that may contribute to both dysfunction and normal aging.

Every cell in the nearly 40 trillion cells in the human body can trace its lineage back to a single, fertilized egg cell which contains the original copy of a person’s DNA. Throughout a person’s lifetime, the cells divide and replace damaged or old cells at different rates based on factors such as their function in the body, would healing and environmental insults.

Even though undergoing elaborate biological quality control checks, each cell division chips away at the genome’s integrity which leaves behind an accumulating number of changes. Principal among these is a dramatic shift in the location and number of methyl groups on the genome which is part of a process that begins during fetal development and continues through a lifetime.

What the researchers found striking about the results from their new method is that they push back the start of that process to the earliest stages of in utero development. Until recently mechanisms behind loss of DNA methyl groups (known as hypomethylation) have largely been unknown. It appears to be more profound in tissues with a high turnover rate such as skin and the epithelium. Typically, tissues with high turnover rates are more susceptible because there are more chances for errors to accumulate. What is being seen is a normal process of cellular aging.

The research project encompassed more than 200 mouse datasets and 340 human datasets the most in-depth study of its kind. The study would not have been possible without massive swaths of accessible data from large-scale sequencing projects.

Reference: Wanding Zhou, Huy Q. Dinh, Zachary Ramjan, Daniel J. Weisenberger, Charles M. Nicolet, Hui Shen, Peter W. Laird, Benjamin P. Berman. DNA methylation loss in late-replicating domains is linked to mitotic cell division. Nature Genetics, 2018; DOI: 10.1038/s41588-018-0073-4

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