Aging in Mice Linked to Misexpression of Class of Genes

Good news! Coming closer to a fountain of youth! This article also covers previous research on the subject of misexpression!

"... A study published December 15 in Science Advances suggests a possible answer, linking the increased activity of genes lacking long stretches of C and G bases with degeneration and aging.

As cells age, the architecture of chromatin, which packages DNA, unravels. ...

Specifically, the researchers focused on stretches of C and G bases called CpG islands (CGI). CGI are present in the promoters of around 60 percent of mammalian genes, termed CGI+ genes, but absent in the remaining 40 percent, called CGI- genes.

These CGI- genes typically lie silent in a densely-packed form of chromatin known as heterochromatin. Heterochromatin attaches to the nuclear lamina, which lines the inner nuclear membrane. As cells age, the nuclear lamina weakens and frees the heterochromatin, which loosens, allowing previously silenced genes to be expressed.  ...
The researchers also investigated whether CGI- genes are connected to what’s known as cellular identity. Cells making up the heart, muscles, kidneys, or other organs usually express different genes to carry out their functions. As cells age, they also lose this cellular identity, and the researchers wondered if misexpression of CGI- genes could help explain why. Analyzing aged mouse kidneys, ... saw that genes typically expressed in the spleen, intestine, eye, and liver start to be expressed in aged kidneys—and the majority of these genes were CGI- genes."

From the abstract:

"Cellular aging is characterized by disruption of the nuclear lamina and its associated heterochromatin. How these structural changes within the nucleus contribute to age-related degeneration of the organism is unclear. Genes lacking CpG islands (CGI− genes) generally associate with heterochromatin when they are inactive. Here, we show that the expression of these genes is globally activated in aged cells and tissues. This CGI− gene misexpression is a common feature of normal and pathological aging in mice and humans. We report evidence that CGI− gene up-regulation is directly responsible for age-related physiological deterioration, notably for increased secretion of inflammatory mediators."

Aging in Mice Linked to Misexpression of Class of Genes | The Scientist Magazine® Genes lacking a particular structure known as CpG islands tend to go haywire in older cells, a study finds, potentially contributing to key facets of aging. But it’s not yet clear if the relationship is causal.

Misexpression of genes lacking CpG islands drives degenerative changes during aging (open access)