Turning back time: ageing reversed in mice

Imagine if we could turn back time. A team that has identified a new way in which cells age has also reversed the process in old mice whose bodies appear younger in several ways. The discovery has implications for understanding age-related diseases including cancers, neurodegenerative disorders and diabetes.
One way all mammalian cells produce energy is via aerobic respiration, in which large molecules are broken down into smaller ones, releasing energy in the process. This mainly occurs in the mitochondria – the "powerhouses" of cells. Mitochondria carry their own genomes, but some of the cellular components needed for respiration are produced partly by the nucleus, so the two must coordinate their activities.
As we age, mitochondrial function declines, which can lead to conditions such as Alzheimer’s disease and diabetes. To investigate why this decline occurs, Ana Gomes at Harvard Medical School and her colleagues compared the levels of messenger RNA (mRNA), molecules that convey genetic information around a cell, for the cellular components needed for respiration in the skeletal muscle of 6 and 22-month-old mice.
They found that the level of the mRNA in the nucleus did not change much between the young and old mice, whereas those in the mitochondria appeared to decline with age.
Similar changes were seen in mice that lacked a protein called SIRT1, high levels of which are associated with calorie restriction and an increased lifespan. These mice also had higher levels of a protein produced by the nucleus called hypoxia inducible factor (HIF-1α).
What was going on? It appears that communication between the nucleus and the mitochondria depends on a cascade of events involving HIF-1α and SIRT1. As long as SIRT1 levels remain high and the two genomes communicate well, ageing is kept at bay. But another molecule called NAD+ keeps SIRT1 on the job; crucially, the amount of NAD+ present in the cell declines with age, though no one knows why, leading to a breakdown in communication.