Stories about the search for eternal youth are as old as literature itself, and while scientists still cannot keep any of us looking forever young, they are gaining new insights into the aging process. For example, evidence is mounting that uncorrected DNA damage, accumulated over the years, is one of the primary causes of aging. In turn, aging is the single largest risk factor for cancer, cardiovascular disease, osteoporosis, diabetes, Alzheimer's disease, and a great many other disorders. A better understanding of why we grow old would be a major step toward slowing the process and extending our years of healthy life. Progress in this field has been stubbornly slow, but help is on the way. Researchers with Berkeley Lab and the University of California at Berkeley have launched the Center for Research and Education on Aging (CREA).

The accumulative effect of senescent cells is starkly evident in the contrast between the smooth skin of a baby and the wrinkled skin of an elderly person.

Judy Campisi is a cell biologist in Berkeley Lab's Life Sciences Division and a leading authority on aging research. Together with Paola Timiras, a UC Berkeley professor emeritus and pioneer in the study of hormonal effects on aging, she helped organize CREA. The two women now serve as CREA's co-directors.

"It is widely recognized that aging is an extremely fertile ground for research and that the Bay Area has a lot of talent in this field, but traditional funding mechanisms are slow," says Campisi. "Often more than a year will go by between when a good research idea is proposed and when it finally gets funded."

The mission of CREA is to generate funding that will support "high-risk pilot or long-term research" projects in the Bay Area, and to educate the scientific community as well as the general public about issues in aging research. One of its first goals will be to establish an endowment for funding aging research. A big step toward this goal was realized in an endowment of several hundred thousand dollars from BioTime, Inc., a Berkeley-based private research firm. The endowment was given in recognition of Timiras's lifetime of accomplishment in aging research and education.

"We want to use this and future endowments to make CREA a major force for mobilizing the research talent in the Bay Area to the study of aging," says Campisi. "There is a long history of aging research and education here and an exceptionally high concentration of world-class biologists. We want to support promising young students and postdoctoral scientists, as well as creative established scientists who are dedicated to understanding and controlling aging."

Campisi herself fits the mold of an established scientist who has dedicated her research to investigating the aging process. Several years ago, she led the development of a technique that made it possible for researchers to identify senescent cells-those that have reached old age-within living organisms.

"Normal cells do not divide indefinitely," explains Campisi. "This trait, termed the finite replicative life span of cells, limits the capacity for cell division by a process termed cellular or replicative senescence. This process is thought to be a tumor suppression mechanism, and also a contributor to the aging of an organism."

Prior to the technique of Campisi and her collaborators, researchers had no way of detecting or studying senescent cells in vivo and therefore had to confine their studies to cells grown in culture. Campisi and her collaborators developed a fast and simple assay based on the discovery that senescent cells produce or express an unusual form of an enzyme called beta-galactosidase that is generally absent in presenescent cells. Employing a stain that turns blue in the presence of beta-galactosidase, Campisi's assay provided the first actual evidence that senescent cells exist in living organisms and that they accumulate with age.

"Age-related decrements in tissue (compare the smooth skin of a child to the wrinkled skin of an elderly person) may, at least in part, derive from an accumulation of senescent cells which cannot proliferate, resist apoptotic death, and have an altered phenotype," says Campisi.

The ability to study senescent cells in living organisms led Campisi to hypothesize that cell senescence, which earlier in life acts to suppress tumors, might later in life contribute to carcinogenesis. An age-dependent accumulation of senescent cells may create what she called a "procarcinogenic" microenvironment that would be conducive to the development of tumors. Recently, experiments done by Ana Krtolica and Simona Parrinello in Campisi's lab have validated this idea. Senescent fibroblasts stimulated the growth precancerous epithelial cells in culture and stimulated their conversion to malignant tumor cells in mice.

"These findings help explain, at least in part, why tumor incidence increases exponentially with age," she says. "Now, we really need a better understanding of whether and how senescent cells affect tissue integrity, and how the senescent phenotype is controlled."

As for the educational component of CREA, Campisi and Timiras envision sponsoring additional courses on aging research at the UC Berkeley campus, plus public and scientific seminars, workshops, and lectures. The first CREA-sponsored symposium, "The New Science of Aging", is scheduled to be held in October, 2001.

CREA's organizers say it will bring to the study of aging an approach that medical schools cannot emulate because their focus is on the study and treatment of specific diseases.

"Preventing or curing any one disease extends the human health span and possibly life span by merely a few years," Campisi says. "If, however, we prevent or ameliorate the underlying aging process, the extension of human health span, and possibly life span, is likely to be much greater."

By helping to integrate the biology talent in the Bay Area and providing speedier and more flexible funding opportunities, Campisi and Timiras hope to answer age-old questions about prolonging youthful health and vigor sooner rather than later.

For more information of CREA, its programs and its funding
opportunities, check the website at http://crea.berkeley.edu/ - end -