Anti-ageing drugs

Scientists have discovered that the genes linked to youthful looks and supple limbs also appear to affect how long we live.

The breakthrough finding could lead to “elixir of life” anti-ageing drugs that would slow down or even put off the development of chronic age-related diseases.

It could even lead to a new generation of cosmetics which help hold back the ageing process and boost overall health.

Researchers found the life-extending secret is all thanks to an increase in the activity of genes that produce both collagen – which is vital to young-looking skin – and other proteins found in the body’s “extra-cellular matrix” (ECM).

This is the framework of scaffolding that supports tissues, organs and bones.

The study focused on strategies known to boost the lifespan of the tiny laboratory worm called C.elegans – or Caenorhabditis elegans – including calorie restriction and use of the drug rapamycin.

Professor Keith Blackwell, from the Joslin (CORR) Diabetes Centre which is part of Harvard Medical School in the US, said: “Any longevity intervention that we looked at, whether genetic or nutritional or drugs, increased the expression (activity) of collagen and other ECM genes, and enhanced ECM remodelling.

“If you interfere with this expression, you interfere with the lifespan extension. And if you over-express some of these genes, the worm actually lives a little bit longer.”

In 2009, it was discovered that rapamycin could extend the lives of mice by more than 10 per cent.

Since then researchers have been investigating whether it could have a similar impact on humans by protecting them against diseases of old age such as cancer and heart conditions.

Although C.elegans is a long way from a human in evolutionary terms, it has been shown to mirror ageing processes in higher forms of life.

Dr Blackwell said: “That’s a strong predictor that this mechanism is relevant to people as well.”

Collagens are the main structural components in connective tissue and make up about a third of the proteins in the human body.

Dr Blackwell said: “Collagens are everywhere. They are like the scaffolding for our tissues, and they give us tissue elasticity and strength.”

ECM structures deteriorate with age and collagens have been implicated in conditions ranging from diabetes complications to heart and artery and kidney diseases.

Separate studies have shown that mice given a treatment that makes them genetically disposed to living longer develop stronger and more elastic muscle tendons.

But until now, no one has looked at the possibility that ECM remodelling might be a defence against ageing.

Instead, work has focused on protecting and regenerating cells.

Dr Blackwell said: “The ageing field really has been focusing on mechanisms that protect or regenerate the cell, but what we’re saying in this paper is that it’s all tied together with the ECM.”

The discovery could lead to cosmetic products that also improve health, according to the team whose findings appear in Nature journal’s online edition.

Elixir of life

It could also lead to the development of improved anti-ageing drugs that would put off the development or slow the progression of age-related chronic disease.

“It says that beauty is definitely not skin deep,” said Dr Blackwell.

“In fact, the richest beauty is inner beauty, because if you want to look young you don’t start with the outside, you start with the inside.

“Cosmetic companies might even consider becoming more like pharmaceutical companies, and looking for drugs that enhance overall health.”

Dr George King, Joslin’s senior vice president and chief scientific officer, who was not involved in the study, added: “This is a very important discovery, which may impact many areas of diabetes development and complications.

“The ECM has been a key component for many studies in diabetic complications including the retina, the heart, the kidney and wound-healing. There’s also a great deal of interest in how the ECM is involved in insulin action as well as in the survival of insulin-producing beta cells.”

The Joslin team’s research required teasing apart two molecular pathways in C.elegans, which live on a diet of rotten fruit that can create a feast-and-famine lifestyle.

Both pathways involve insulin and insulin-like growth factor 1 (IGF-1), a hormone with a molecular structure very similar to insulin.

One pathway allows the worm to do a version of hibernation, so that it can better endure extremes of temperatures or lack of food or other stresses, and then resume normal life in better times.

The second pathway, the main focus of the study, more closely parallels human mechanisms and requires activation of a gene known as SKN-1 in the worm.

This is a “master gene regulator” that controls many defences against stress.

Lead author on the study Collin Ewald, said: “Ageing is a complex process in which maintenance of tissues declines over time.

“The ultimate goal of ageing research is to find processes that promote healthy ageing by ensuring the quality of youthfulness late in life.”

Gene therapy to treat cystic fibrosis

A gene therapy has stabilised and slightly improved cystic fibrosis in some of 136 patients in a trial.

Their lungs showed no decline, on average, after they inhaled healthy copies of the gene that causes CF once a month for a year, results published in Lancet Respiratory Medicine show.

And the lungs most clogged before the trial showed a 3% improvement.

The lungs of patients that did not take the gene therapy showed a decline of 3-4% on average over the same period.

Prof Eric Alton, of Imperial College London, who led the trial, warned: “The effect is modest and it is variable. It is not ready to go straight into the clinic yet.”

Prof Alton and his colleagues at the UK Cystic Fibrosis Gene Therapy consortium, which includes scientists at Edinburgh and Oxford Universities as well as Imperial, are hoping to have a further trial next year.

Cystic fibrosis
Cystic fibrosis

Cystic fibrosis is an inherited condition caused by a faulty gene that leads to a build up of sticky mucus causing debilitating infections in the nose, throat and lungs.

Patients’ average life expectancy is 41.

Prof Stuart Elborn, of Queen’s University in Belfast, said the results were “encouraging” but the therapy had been no more effective than some of the drugs currently available.

And he called for more small-scale tests to see if a larger dose would be more effective.

“If I was on the board of a pharmaceutical company, I would require further studies to determine the best dose and whether the current treatment could be combined with other drugs to increase the effect,” he said.

“It is too soon to proceed with larger phase-three trials costing many millions”.

Cystic Fibrosis Trust chief executive Ed Owen said: “The advantage of gene therapy is that it attacks the basic defect of cystic fibrosis and that has the potential to reduce the daily routine of drugs that those with cystic fibrosis endure each day and (offers the possibility) of long-term improvement to transform their lives”.