Aging Associated with Systemic Length-Associated Transcriptome Imbalance; Aging Is Accompanied by Shift in Gene Activity Toward Shorter Gene Transcripts, Which Are Associated with Accelerated Aging; Longer Gene Transcripts Associated with Longer Lifespan

Northwestern University researchers have discovered a previously unknown mechanism that drives aging. In a new study, researchers used artificial intelligence to analyze transcriptomic data from a wide variety of tissues, collected from humans, mice, rats, and killifish. The scientists discovered that the length of gene transcripts can explain most molecular-level changes that occur during aging. All cells must balance the activity of long and short genes. The researchers found that longer genes are linked to longer lifespans, and shorter genes are linked to shorter lifespans. They also found that aging genes change their activity according to length. More specifically, aging is accompanied by a shift in activity toward short genes. This causes the gene activity in cells to become unbalanced. Surprisingly, this finding was near universal. The researchers uncovered this pattern across several animals, including humans, and across many tissues (blood, muscle, bone, and organs, including liver, heart, intestines, brain, and lungs) analyzed in the study. The new finding potentially could lead to interventions designed to slow the pace of--or even reverse--aging. The open-access article was published on December 9, 2022 in Nature Aging, and is titled “Aging Is Associated with a Systemic Length-Associated Transcriptome Imbalance.”