Cause of aging reversed in mice—human trials starting in 2014

Posted by: on Jan 2, 2014 | No Comments

little mouseResearchers have managed to reverse the effects of aging in mice using an approach that restores communication between a cell’s mitochondria and nucleus. Mitochondria are the power supply within the cell, generating the chemical energy required for key biological functions. When communication breaks down between mitochondria and the cell’s control center, the nucleus, the effects of aging accelerate.

A team led by David Sinclair, a professor from UNSW Medicine who is based at Harvard Medical School, found that by restoring this molecular communication, aging could not only be slowed, but could be reversed. The technique has implications for treating cancer, type 2 diabetes, muscle wasting, inflammatory and mitochondrial diseases.

The study follows on from previous research showing that exercise and certain dietary habits, such as calorie restriction or the intake of resveratrol (found in red wine and nuts), slowed the breakdown of intra-cellular communication and therefore aging.

Responsible for this breakdown is a decline of the chemical (nicotinamide adenine dinucleotide) NAD. By increasing amounts of a compound used by the cell to produce NAD, Professor Sinclair found that he could quickly repair mitochondrial function.

“It was shocking how quickly it happened,” co-author Dr Nigel Turner, an ARC Future Fellow from UNSW’s Department of Pharmacology says. “If the compound is administered early enough in the aging process, in just a week, the muscles of the older mice were indistinguishable from the younger animals.”

NAD was administered to mice in hopes that it would slow the aging of skeletal muscle. The researchers were shocked to find that it didn’t slow aging; it dramatically reversed it. In under a week, the mice who had previously been suffering from a variety of age-related impairments experienced an increase in muscle tone, as if they had been exercising and following a healthy diet.

NAD is involved in redox reactions, which regulate electron transfer in metabolic processes. As the mice grew older and less active, their levels of NAD had basically been cut in half. By replenishing this critical compound in the mice, their muscles had been rejuvenated. The natural process that deteriorates skeletal muscle is the same one that affects the heart.

Looking for indicators of insulin resistance, inflammation and muscle wasting, the researchers found that the tissue of two-year-old mice given the NAD-producing compound for just one week resembled that of six-month-old mice. They said that this is comparable to a 60-year-old human converting to a 20-year-old in these specific areas.

They also found that young mice given the same compound became “supercharged” in certain aspects, suggesting that the technique could have benefits for young, healthy humans as well.

Another significant finding, with possible implications for cancer treatment, was the involvement of the chemical HIF-1. This chemical is responsible for the disruption of communication within the cell and is naturally produced by the body when deprived of oxygen. Cancer is also thought to be responsible for activating HIF-1 and the researchers have now found it also switches on during aging.

“It’s certainly significant to find that a molecule that switches on in many cancers also switches on during aging,” said Ana Gomes, a postdoctoral scientist in the Sinclair lab. “We’re starting to see now that the physiology of cancer is in certain ways similar to the physiology of aging. Perhaps this can explain why the greatest risk of cancer is age.”

The researchers are now looking at the longer-term outcomes of the NAD-producing compound in mice and how it affects the mouse as a whole, including whether it will give the mice a longer, healthier life.

“There’s clearly much more work to be done here, but if those results stand, then aging may be a reversible condition, if it is caught early,” says Professor Sinclair.

Human trials of NAD treatments will begin in 2014. However, the treatments will not be cheap. In order to gather enough patients to do the study properly, millions of dollars will need to be raised. Though there is no telling how long it will be before this treatment hits the market, Dr. Sinclair has established a company to expedite the process if and when it is granted approval.