The core principle behind aging is still an unsolved mystery and a problem with a wide variety of potential answers. Recently, by focusing on the length change of genes in humans and mice, Luís Amaral and his collaborators in Northwestern University reveal a convergent changes as aging occurs in a molecular level: longer genes tend to be more likely to become less active than shorter ones when people grow older.
Thomas Stoeger, a postdoctoral scholar in Amaral’s lab, proposed this direction of length measurement after the team found little correlation between specific gene type and aging. The team then applied machine-learning algorithms on male mice aged 4, 9, 12, 18, and 24 months old to collect the most common changes on their RNA in 17 different tissues. The RNA level is a reflection of the transcription ability of corresponding DNA, and could hence identify gene transformation across mice of different ages. Computer simulation, therefore, unravels a consistent pattern that longer transcripts became less abundant than shorter transcripts in older animals across all measured tissues in heart, kidney, and brain.
To establish that their gene length theory still holds in human and other animals, the team repeated the experiment on postmortem human tissue and tissues extracted at specific ages in other animals. Surprisingly, the findings on various organisms still attest to the hypothesis on the significance of gene length in aging procedure even taking the immense diversity of living conditions of human into account. Amaral comments that“The fact that you find the same pattern despite this diversity really says that this is something robust,” he says. “That result dramatically increases my confidence in this being a true and important pattern.”
Taking a closer look at the specific types of genes and their transcripts that remain the longest and the shortest, scientists discover correlation between gene functions and longevity and a shorter life, respectively. Specifically, the longest transcripts are related to longevity, including neuronal activity, while the shortest ones are involved in immune function. Consequently, antiaging drugs can aim at increasing the activity of longer gene to mollify or even reverse aging process.
The study shows accordance with previous research, evidencing that the accumulation of DNA damage during aging has a stronger effect on longer genes; the longer the gene is, the more likely it is to develop a problem that cannot be repaired, says Maria Ermolaeva, a group leader at the Leibniz Institute of Aging in Germany.
However, the research on gene length fails to show a causal relationship with aging. João Pedro de Magalhães, a professor of molecular biogerontology at the University of Birmingham in England, clarifies the possibility that “It could be that length-associated transcriptome changes are simply a reflection of other aging-related processes, such as an uptick in immune system activity.” Stronger evidence is still in need to settle down the mystery.
Source: https://www.scientificamerican.com/article/aging-is-linked-to-more-activity-in-short-genes-than-in-long-genes/