Theory 8 of Why We Age.
Systemic length-associated transcriptome imbalance

Transcript length alone explains most transcriptional changes observed with aging in humans. Transcripts are mRNA molecules transcribed from DNA.  The length reflects how many GCAU nucleotides are linked in the transcript, which will then often be translated into proteins.

Three lines of evidence support the biological importance of the uncovered transcriptome imbalance.  “First, in vertebrates the length association primarily displays a lower relative abundance of long transcripts in aging. Second, eight antiaging interventions of the Interventions Testing Program of the National Institute on Aging can counter this length association. Third, we find that in humans and mice the genes with the longest transcripts enrich for genes reported to extend lifespan, whereas those with the shortest transcripts enrich for genes reported to shorten lifespan.”

This is indeed one of the most important papers on aging in recent times and opens a new window on aging. “Aging is associated with a systemic length-associated transcriptome imbalance”. Eight antiaging interventions of the Interventions Testing Program of the National Institute on Aging can counter this length association.

There is support for a preferential fold increase of long transcripts for 7 interventions: fibroblast growth factor 21 (FGF21) excess, Myc heterozygosity, rapamycin, resveratrol, S6 kinase 1 (S6K1) deletion, senolytics and Snell mice. We did not find statistically significant support (P > 0.01) for the 4 remaining interventions: Ames mice, eating every other day, Little mice and metformin.  But this conclusion is not totally clear.

We can conclude that the length-associated transcriptome imbalance is responsive to antiaging interventions and that several interventions promoting longevity oppose the direction of the transcriptome imbalance that we are reporting here to be the primary direction of the relative fold change encountered within vertebrates. We thus conclude that the length-associated transcriptome imbalance is responsive to antiaging interventions.