Turning back time: ageing reversed in mice

Aging…No longer inevitable, for mice (Image: Design Pics Inc/Rex)

New Scientist: 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 from 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.

Turning back time

The team wondered if this aspect of ageing could be reversed by increasing the amount of SIRT1 in the cells. To find out if that was possible, they injected 22-month-old mice twice daily for a week with nicotinamide mono nucleotide (NMN) – a molecule known to increase levels of NAD.

At the end of the week, markers of muscular atrophy and inflammation had dropped and the mice had even developed a different muscle type more common in younger mice. Together, these features were characteristic of 6-month-old mice.

"We found that modulating this pathway can improve mitochondrial function and age-associated pathologies in old mice, and therefore it gives a new pathway to target that can reverse some aspects of ageing," says Gomes.

"This paper clearly demonstrates that NAD+ production is a sort of 'Achilles' heel', [a lack of which] significantly contributes to ageing, and also that this problem can be ameliorated by boosting NAD+ production with key intermediates, such as NMN," says Shin-Ichiro Imai, at Washington University School of Medicine in St Louis, Missouri.

Journal reference: Cell, DOI: 10.1016/j.cell.2013.11.037

Ibuprofen May Help Stave Off Parkinson's

Finding suggests need to look closer at the disease as inflammatory, expert says, “ Ibuprofen may help stave off Parkinson’s, ALS, or Lou Gehrig’s Disease.”

WEDNESDAY, Feb. 17 (HealthDay News) -- Regular use of ibuprofen, a common anti-inflammatory drug, significantly lowers the risk for developing Parkinson's disease, Harvard researchers report.

People who took three or more tablets a week showed a 40 percent lower risk than those who didn't take the common pain reliever, their study found.

Study author Dr. Xiang Gao, an instructor and epidemiologist at Harvard Medical School and Brigham and Women's Hospital in Boston, said the findings are important for anyone at increased risk for Parkinson's because most people with the disease eventually become severely disabled.

"There is thus a need for better preventive interventions," Gao said. "In this context, our findings regarding the potential neuroprotective effect of ibuprofen, one of the most commonly used analgesics, on Parkinson's disease may have important public health and clinical implications."

Parkinson's is a disease that affects nerve cells in the brain that control the movement of muscles. It affects an estimated 1 million people in the United States, men far more often than women. The exact cause is unknown, but experts believe it's a combination of genetic and environmental factors.

Gao said that though the drug levodopa is the current standard treatment for Parkinson's, much more is needed. He is scheduled to present the findings in Toronto at the annual meeting of the American Academy of Neurology in April.

The findings came from an analysis of data on 136,474 people who did not have Parkinson's at the start of the study. In a six-year span, 293 were diagnosed with the disease. Those who took the largest doses of ibuprofen were less likely to have developed Parkinson's than were those who took smaller amounts of the drug, the study found.

No other pain reliever was found to lower the risk for Parkinson's.

Dr. Michele Tagliati, an associate professor of neurology and director of the Parkinson's Disease Center at the Mount Sinai School of Medicine in New York City, described the results as somewhat surprising and said they emphasized the need for further study.