It's not as catchy as "You're as young as you feel," but from a scientific standpoint, you may be as young as your electron transport chain.

That's the conclusion suggested by a study published in the July 2006 issue of the open access journal PloS Genetics.

The study, senior author Stuart Kim told BioWorld Today, "lets you look at young vs. old people at a molecular level."

Kim, a professor of genetics at Stanford University, said that currently, aging can be assessed only "at a very superficial level" - basically, assessing age comes down to, literally, eyeballing. "Even with a microscope, it's often hard to tell the difference between young and old tissue."

But of course, aging can be measured much more precisely. In aging tissue, "there are hundreds of genes that are changing."

250 genes, to be exact - at least in human muscle tissue. That's the number of genes Kim and his colleagues from Stanford University, the Palo Alto Veterans Affairs Health Care System and the National Institutes of Aging, of Baltimore, found that changed their expression level with age.

The researchers sampled muscles from subjects ranging in age from 20 to more than 80 years. Of the 250 genes, exactly half increased in expression levels; the other half decreased.

The scientists next tried to determine whether there are whole pathways whose genes are jointly up- or downregulated during aging, and then compared their results to the results of studies done in the kidney and the brain. They found six pathways that are commonly affected in all three tissues.

The researchers also wanted to see how evolutionarily conserved such aging markers are, and compared humans to mice, flies and worms.

They found that one particular pathway - the electron transport chain pathway, which produces the cellular energy currency, adenosine triphosphate, or ATP - was decreased in mice and flies, but was unchanged in the worm species C. elegans.

Even the cross-species consistency between humans and mice is "surprising, because they have such vastly different lifespans," Kim said. The electron transport chain proteins "must be decreasing very rapidly in real-time in the flies."

C. elegans worms, who live only for two weeks, may not live long enough to show changes in the electron transport chain by the microarray method. Kim noted that other experimental evidence does implicate the electron transport chain in aging in C. elegans: Expression of the pathway can be reduced via genetic methods, and "the easiest way to make a worm live longer is to decrease the expression of that pathway."

Taken together, the two lines of evidence suggest that downregulation of the electron transport chain could be a protective mechanism against aging, though Kim stressed that, at this point, all his research has done is to show a "molecular phenotype" of aging, without determining whether the changes in gene expression his group observed are good or bad from the point of view of slowing down aging: "Whether that's helping you or hurting you or having no consequences, we don't know."

Kim and his team plan to address that question by comparing how natural variation in the expression levels of muscle genes compare to physiological function of the muscles - that is, whether people with higher levels of electron transport chain proteins have physiologically younger or older muscles than their counterparts.

The scientists already have used statistics to determine whether there was a relationship between gene expression and physiological age of the muscle - that is, whether a sample of 60-year-old muscle that performed like younger muscle physiologically also would have a "younger-like" gene expression signature on the microarray.

When chronological age was taken into account, the scientists found a partial correlation of 0.2 between gene expression profile and physiological age of the muscle. Statistically significant or not, 0.2 is a weak correlation; but Kim believes that the correlation is weak mainly because the anatomical difference between old and young muscle is fairly subtle.

"It's pretty hard to tell an old muscle from a young muscle just by looking at it," Kim explained, and noted that in previous experiments his lab had done with kidney tissue, the correlation between physiological performance and age of gene expression signature had been between 0.7 and 0.8.

In clinical medicine, the gene expression signature could have diverse uses. For one thing, about one-third of old kidneys remain suitable for transplant; it's finding them that currently bedevils transplant surgeons. Given the shelf life of organs for transplant, by the time it can be established that a kidney is suitable for transplant, it no longer is. Kim noted that there is no time to do a gene expression profile of a potential donor kidney either, but if the microarray profiling can be made faster, "it could open up a large pool of potential organ donors."

Even if the method does not get any faster, it could shave time - decades in fact - off of the wait to see whether an anti-aging drug has any effect. Changes in age's molecular signature might be apparent in a few months; in contrast, Kim said, given the human lifespan, "I could have a great drug today and it would take me 30 years to know."