Old as your genes

A fingerprint of gene activity could reveal the true 'youthfulness' of our kidneys, hearts and muscle, regardless of our biological age. The technique might one day be used to find healthy organs for transplants or to warn us of impending disease.

It's hard to tell, particularly on a cellular level, whether a young and healthy body conceals a withering heart — or conversely, whether an old man has a vigorous ticker like that of a younger man.

Stuart Kim of Stanford University Medical Center, California, says that a simple genetic test might do the trick. He and his colleagues have found a set of genes whose activity reveals how well organs are operating, regardless of their owner's actual age.

The team analysed the activity of thousands of genes in 81 muscle samples from people aged between 16 and 89. They pulled out a set of 250 genes whose activity goes markedly up or down with age.

When they compared the activity of these genes with the muscle fitness of individuals, measured by the size of their muscle fibers, they found that the genetic profile, rather than a person's age in years, was a more accurate indicator of fitness.

Body clock

The speed with which our cells and bodies deteriorate is determined partly by the genes we inherit from our parents and partly by the ravages of living. These factors can change the rate at which certain genes manufacture proteins, and other aspects of the cell's machinery. Some studies, for example, have shown that the ends of chromosomes, called telomeres, decay over time and do so faster in those who indulge in unhealthy activities such as smoking.

Kim's team found one 64-year-old man who had a pattern of gene activity more like that of a younger person. Indeed, under the microscope, his muscle appeared young; it contained bigger 'fast twitch' fibers that are good for sprinting and more prevalent in young muscle. The findings are reported in the journal PLoS Genetics1.

In an earlier study, the same group detected a 78-year-old woman with a kidney more like that of a centenarian, according to her genetic profile and an inspection of the tissue under the microscope2.

The researchers found that aging affects some of the same genes across many different tissue types and in many different animals. One group of genes, which is involved in generating energy in the cell's mitochondria, quiet down with age in human muscle, kidney and brain tissue, and also in aging mice and flies, even though these animals have very different lifespans.

It may be that this pathway is a weak spot in the cell that is particularly vulnerable to aging, Kim says.

Healthy living

Kim says that such techniques could one day be used to identify donor organs that are normally ruled out because of the donor's age but may actually be in good working order. "We could open up a huge new pool of donors," Kim says, who is planning a study to test this idea.

In future, a routine blood test at the doctor's office could also reveal the true working condition of organs, allowing patients to modify their lifestyle or diet to rejuvenate their bodies.

But to do this researchers will need to find a way to gauge the activity of an organ's genes from molecules in the blood rather than from a tissue sample, which is difficult to obtain.

Source:
news @ nature.com