Gene activity shifts nonlinearly in the aging mouse colon

Researchers analysed 83 tissue samples across five adult ages to track gene activity in the colon of male mice. Instead of changing in a steady line, gene activity followed multiple patterns at once across life. Many genes peaked or dipped during midlife, which would be missed in comparisons limited to young and old animals. A major transition occurred between midlife and late life, marked by a collapse of the unfolded protein response, a quality-control process for handling misfolded proteins. The authors also described age-dependent patterns in RNA transcripts containing transposable elements, DNA sequences that can move within the genome. In addition, transcriptomic entropy, a measure of disorder in gene activity, changed nonlinearly across the lifespan. Finally, the team identified three genes that tracked chronological age and used them to construct a compact transcriptomic clock, which they validated with independent data.