Aging and Transcript Length

In an article published in Trends in Genetics  and featured on the front page of cell.com,  Thomas Stoeger, PhD and collaborators showed that biological aging is associated with decreased expression of longer genes. To describe this phenomenon, found in multiple species including humans, Stoeger and his coauthors introduced the term gene-length-dependent transcription decline (GLTD).

Cell types such as neurons are particularly susceptible to GLTD. One reason is that neurons express long genes, including some of the longest genes known. Another reason is that neurons are postmitotic, so they have more opportunity over their long lives to accumulate DNA damage. These factors predict that GLTD would be seen in Alzheimer's disease—which is what researchers have found. In addition, GLTD is observed under other conditions known to accelerate biological aging.

This article, shared widely in a news releases from both Cell Press and Northwestern University and reported by Medical News Today, expanded on earlier research published in Nature Aging that was featured on Northwestern Now and highlighted by the National Institute on Aging. More recently, this discovery was featured in a Front Matter report published in PNAS. 

A new focus on the molecular-level physical processes of aging could provide new insights on old genomic datasets, paving the way for new diagnostic tests or therapeutic targets. As Stoeger told PNAS, "There could be paradigm shifts in interventions, and a new class of biomarkers and interventions that are conceptually different from what others have done in the past."

• Soheili-Nezhad S, Ibáñez-Solé O, Izeta A, Hoeijmakers JHJ, Stoeger T. Time is ticking faster for long genes in aging. Trends in Genetics. 2024; 40(4):299-312.
• Stoeger T, et al. Aging is associated with a systemic length-associated transcriptome imbalance. Nature Aging. 2022; 2(12):1191-1206.