Discovery of stable genes offers insights into aging and longevity

A new research paper was published in Aging (Aging-US) on January 27, 2025, in Volume 17, Issue 1, titled "Age-invariant genes: multi-tissue identification and characterization of murine reference genes."

Aging is a process driven by changes in gene activity, but researchers from Yale University School of Medicine and Altos Labs, led by first author John T. González and corresponding author Albert T. Higgins-Chen, have identified a set of genes that remain unchanged throughout the aging process. This discovery could improve the accuracy of aging research and provide insights into why some genes stay unchanged while others decline.

"Reference genes have mostly been identified and validated in young organisms, and no systematic investigation has been done across the lifespan."

The study looked at gene activity in 17 different tissues in mice, from 1 month old to over 21 months old. Scientists used advanced bioinformatic analysis methods to analyze RNA sequencing data. They found nine genes that stayed the same across all tissues, as well as other genes that remained stable in specific tissues. These genes are usually shorter and have special DNA regions called CpG islands, which may help cells stay healthy and resist aging. Their stability throughout aging was confirmed by analyzing different datasets and using RT-qPCR.

One of the most significant findings is that these stable genes are linked to essential cellular functions, such as mitochondrial activity and protein maintenance. This challenges the common belief that all aspects of aging involve gene dysregulation. Instead, the findings suggest that some cellular processes may naturally resist aging, leading the way for new research on longevity and potential anti-aging therapies.

"Biological processes that change with age and those that resist age-related dysregulation are two sides of the same coin, and both will need to be investigated to fully understand aging."

Another key finding is that commonly used reference genes, such as GAPDH and ACTB, fluctuate with age, making them unreliable for aging studies. No single classical reference gene was found to be stable across all tissues. Researchers often use these reference genes as a control to measure gene activity, but if their expression changes over time, it can lead to inaccurate results. By identifying new, stable reference genes, this study provides scientists with better tools for studying aging-related diseases, regenerative medicine, and longevity science.

Understanding how certain genes remain unchanged throughout life suggests that they may play a protective role in aging and could potentially be used to develop treatments that slow down age-related decline. While further research is needed, this discovery sets a new standard for measuring gene activity in aging studies and could have a significant impact on aging research and medicine.