Fast-forward Aging

By Josie Glausiusz|Friday, November 01, 1996
RELATED TAGS: GENES & HEALTH, AGING
Cataracts, osteoporosis, heart disease, and other such ills typically afflict only the aged. For the unfortunate sufferers of a disease called Werner’s syndrome, however, these ailments strike not in the seventh or eighth decade of life but the third. Such people age abnormally fast and usually die before they reach 50.

Recently, molecular geneticist Gerard Schellenberg and his colleagues at the Veterans Affairs Medical Center in Seattle traced the gene that causes the disease to a site on chromosome 8. When they then compared the gene’s dna sequence with those of previously identified genes, they found that it closely matched genes known to code for a class of enzymes called helicases, which unwind the double helix of dna.

Helicases--of which there are many different types--are crucial components of all living cells. They help repair dna and enable messenger rna molecules to ferry genetic instructions from the nucleus, where dna resides, throughout the cell, where the instructions are biochemically translated into proteins. Almost any cellular function that uses dna or rna is going to involve a helicase, says Schellenberg. If you’re going to replicate dna, you’ve got to unwind the two strands before you can copy it; you’ve also got to unwind it before you can repair it. You’ve got to unwind it to transcribe it. When chromosomes segregate during cell division, you have to untangle a bunch of chromosomes, and that requires a helicase.

Schellenberg and his colleagues don’t yet know exactly what role the new helicase plays within the cell. They suspect that the enzyme is not one that is essential to life but is somehow conducive to a long and healthy one. It’s probably not required for dna replication, because that would be lethal, he explains. On the other hand, it could be involved in dna repair--or in preventing mutation during dna synthesis. Of the two theories, Schellenberg favors the second, since tests have shown that damaged dna from people with Werner’s does seem capable of repairing itself. Despite this, their dna seems to accumulate mutations at a higher- than-normal rate. Perhaps, he speculates, the untangling of dna that occurs prior to cell division goes awry--resulting in breaks in the dna that amass over time and overwhelm the cell’s ability to fix them.

One possibility, Schellenberg says, is that accumulated dna damage sooner or later interferes with the cell’s ability to divide. That could explain why skin cells from young people with Werner’s have such a short shelf life; when cultured, they go through very few cell divisions. In fact, their cells behave in the same way as those of the truly elderly.

Might it be possible someday to use a form of gene therapy to cure the disease? Theoretically, says Schellenberg. The problem is that people with Werner’s syndrome have so many different organs that are messed up. So you’d have to give gene therapy all over the body. Trying to get a helicase into every cell in the body--I don’t think it’s theoretically impossible--it’s just so far over the horizon right now.

Understanding how the gene works, says Schellenberg, could also provide insight into normal aging. It may be that normal people carry variants of the gene that influence their life spans or predispose them to an earlier death--a possibility he is now investigating. It could be that those who carry one defective copy of the gene (unlike Werner’s patients, who have two) may develop disorders associated with aging, like cancer, when the normal version of the gene is altered by some environmental factor--radiation or toxins, perhaps. Studying Werner’s, he says, could help pinpoint the mechanism that underlies all diseases of aging, which appear in part to be due to the cell slowdown that is such a dramatic feature of this disease.

The reason we’re studying Werner’s is so that we can get at that underlying mechanism, says Schellenberg. When you see something go wrong, then you’ve got a handle on what happens when things go right.
Comment on this article
ADVERTISEMENT

Discover's Newsletter

Sign up to get the latest science news delivered weekly right to your inbox!

ADVERTISEMENT
ADVERTISEMENT
Collapse bottom bar
DSCOctCover
+

Log in to your account

X
Email address:
Password:
Remember me
Forgot your password?
No problem. Click here to have it emailed to you.

Not registered yet?

Register now for FREE. It takes only a few seconds to complete. Register now »