When aging gets fast-tracked

Certain molecules known as non-coding RNAs may help fend off the effects of age.

Mice that lacked Norad showed early signs of aging; for example, their spine became abnormally curved at a young age. Image credit: Kopp et al. (CC BY 4.0)

Only a tiny portion of our genetic material contains the information required to create proteins, the workhorses of the body. The rest of our DNA, however, is not useless: some of it can be transcribed to create molecules known as non-coding RNAs, which are increasingly scrutinized by scientists.

For example, a non-coding RNA called NORAD acts as a guardian of the genome by reducing the activity of a protein named PUMILIO. Without NORAD, PUMILIO becomes overactive, and this causes problems as genetic information is split between two ‘daughter cells’ when a cell divides.

Defects in the amount of genetic material in cells have been linked with faster aging in animals. In addition, some studies suggest that as animals get older, the levels of NORAD in the body decrease, while the levels of PUMILIO increase. However, the precise role that NORAD may play in aging remains unclear.

To address this question, Kopp et al. engineered mutant mice that lack Norad (the mouse equivalent of human NORAD) and carefully monitored how they grew and developed. The animals looked normal at birth, but they seemed to age faster: for instance, their fur became thin and gray, and their brains developed age-related abnormalities much sooner than normal mice.

At the level of individual cells, losing Norad was also associated with problems often seen in old age. The mutant animals were more likely to have incorrect amounts of genetic information in their cells, and they had defects in the cell compartments that create the energy necessary for life. Further experiments showed that these issues were driven by PUMILIO being hyperactive. Overall, the work by Kopp et al. reveal that the non-coding RNA Norad is essential to keep PUMILIO activity in check and to prevent problems associated with aging from appearing in young animals. Further studies are now needed to take a closer look at how NORAD and other non-coding RNAs keep us healthy.