Key symptom of old age reversed 'surprisingly easily', study finds

Human clinical trials underway after blood vessel boosting chemical was able to reverse muscle loss and improve endurance in mice

The loss of muscle mass and fitness in old age may be reversible by providing the body with a key molecule it needs to rebuild blood vessels, scientists have found.

The arteries and capillaries which transport oxygen and nutrients around the body are not replaced as quickly when we’re older and this leads muscles to tire more quickly. Eventually they start to atrophy from under use.

But new research showed this process was “surprisingly easy to reverse” in elderly mice by supplementing a key ingredient which helps maintain and rebuild the inner lining of blood vessels.

It resulted in a new tangle of blood-carrying capillaries which reversed muscle loss and saw the endurance of the creatures improve by as much as 80 per cent.

Researchers from Australian and US universities, including Harvard and Massachusetts Institute of Technology (MIT) were part of the team that conducted the study.

A treatment to restore fitness and combat frailty in old age would be a major step towards living longer, healthier lives as it would mean older people could stay active and independent and reduce the risk of them ending up in hospital.

While there's no guarantee the same effect would occur in humans, the findings were so impressive that the group have already begun clinical trials looking at whether the results can be replicated.

“We’ll have to see if this plays out in people, but you may actually be able to rescue muscle mass in an aging population by this kind of intervention,” said one of the study’s senior authors, Leonard Guarente a Professor of Biology at MIT.

“There’s a lot of crosstalk between muscle and bone, so losing muscle mass ultimately can lead to loss of bone, osteoporosis, and frailty, which is a major problem in aging.”

The research published in the journal Cell explains that researchers looked at the cells which make up the inner lining of blood vessels in mammals.

One of the key components is a member of a family of protein molecules called surtuins.

These have been dubbed “longevity proteins” in other studies looking at their impact in aging. The researchers began by deleting the area of the genetic code in mice which allows them to manufacture one type, sirtuin one.

They found that at six months old these mice had a much less extensive network of blood-carrying capillaries, and about half the fitness, when compared to mice that were still able to produce it.

After seeing the effect of the absence of sirtuin one, they decided to see whether the reverse would hold true if they boosted its levels in older mice.

“In normal aging, the number of blood vessels goes down, so you lose the capacity to deliver nutrients and oxygen to tissues like muscle, and that contributes to decline,” said Guarente.

The team focused on an enzyme, NAD, which activates sirtuin one but its production slows down with age and it begins to break down more quickly in the body as well.

To create NAD the body needs another substance, nicotinamide mononucleotide (NMN).

Eighteen-month-old mice - a rodent “old age” equivalent to mid-fifties in humans - were given NMN for two months and saw their network of capillaries restored to levels seen in young mice.

This led to an increase in endurance, measured by the length of time they could keep running on a treadmill, of 56 to 80 per cent.

“In this study, we show that a decrease in NAD [in the inner lining of the blood vessels] is a primary reason why our ability to exercise and receive its benefits diminish as we age,” the study says.

They now think that NAD-boosting chemicals can counteract this decline and allow the body to keep remodelling blood vessels.

Adding that even at 32 months – roughly the equivalent of a human in their eighties – capillary loss was “surprisingly easy to reverse”, the first time such an effect has been shown.

“The approach stimulates blood vessel growth and boosts stamina and endurance in mice and sets the stage for therapies in humans to address the spectrum of diseases that arise from vascular aging,” said fellow senior investigator David Sinclair a professor in the Department of Genetics at Harvard Medical School.