This is part of an ongoing series of interviews by CREA with workers in the field of aging.

Dr. Judy Wong

UCB Postdoctoral, Collins Lab

Judy Wong is a postdoctoral in the lab of Professor Kathy Collins in the Department of Molecular and Cell Biology at the University of California at Berkeley. The Collins lab's primary focus is telomerase, a protein involved in both aging and cancer.

The ends of our chromosomes are capped with long repeating DNA sequences called telomeres. Telomeres serve as structural markers, preserving the distinct DNA contents of each chromosome from various cellular processes that would otherwise alter them. However, the machinery that copies our DNA during cell division cannot completely replicate telomeres, resulting in partial telomere loss after each cell division. Without further intervention, cell division eventually renders telomeres critically short, resulting in chromosome alteration and, ultimately, cell death or excessive cell proliferation, as in cancer.

Happily, evolution has a solution to this state of affairs: normal cells keep themselves under control by recognizing when their telomeres are too short and entering a state termed senescence, after which they will no longer divide. Thus, most cells are programmed to sacrifice their own reproductive ability for the good of the entire organism.

The enzyme telomerase can prevent both senescence and chromosome alteration in normal cells. Its function is to add additional telomeric repeats to chromosome ends, restoring telomere length and extending the number of cell divisions possible. But there's a catch: except for when we're in the womb, most of our cells lack telomerase most of the time. Two notable exceptions are germ cells (which must divide endlessly to sustain life) and bone marrow.

Biologists have known this general picture for years. But they still don't understand the full role played by short telomeres, telomerase (or its absence), and senescence in the pathologies brought on by age. This relationship is what interests Wong.

In her current role, Wong is studying X-linked dyskeratosis congenita (DKC), a rare disease of the bone marrow associated with failure of the immune system and, in most cases, death in childhood. X-linked DKC patients show a mutation in the gene dyskerin, which plays a role in the proper assembly and accumulation of telomerase. The Collins lab has shown that it is this deficiency of telomerase in bone marrow (where white blood cells are produced) which results in DKC-related immune system failure.

Wong's studies may have implications beyond X-linked DKC to pathologies of normal aging. There is evidence that some aging-related organ failures are related to cell senescence induced by telomere shortening.

Further work on cultured human cells may pave the way for telomerase replacement therapy as a cure for X-linked DKC. Such a therapy, should it ever appear, would raise an interesting dilemma: although telomerase sometimes prevents cancer by preserving chromosome structure, in some cases it also encourages cancer development by allowing endless cell proliferation. So, if you have X-linked DKC, telomerase therapy may give you a functioning immune system in the short term but increase your risk of cancer in the long term.

Since most X-linked DKC patients fail to survive childhood, however, Wong sees the entire issue as one of "cost-benefit analysis -- I'm certainly not advocating, 'Let's inject everyone with telomerase', but if you're suffering from DKC and only have five years to live, it's probably worthwhile to think about."

An appointment studying telomerase seems a natural fit for Wong, by training a pharmacologist who "likes enzymes". Her doctoral thesis at the University of Toronto concerned dioxin, cancer, and genetics. Dioxin is a known carcinogen, but only a certain portion of the population develops cancer after exposure to it. Wong showed that there may be a genetic basis for this difference.

Of the general phenomenon of aging, Wong defines it as a "multifactorial syndrome," of which telomere loss is but one consequence. "People are coming to realize that aging is one of the more pressing problems" in our society, she says, and her long-term research goal is to support healthy aging. At the same time, though, she's a bit concerned about some questionable solutions already on the market: "One of the things [Professor Kathy Collins] brought into the lab is a bottle of topological 'anti-aging' creme with telomerase as an ingredient." We're fairly sure that any benefits you'd see from applying such a product are strictly psychological. But if Judy Wong's continued research is successful, the future may hold more effective treatments for the pathologies of age.