In an effort to extend healthy lifespan in people, researchers funded by the Glenn Foundation for Medical Research gathered on June 8 at HMS to discuss issues of aging in different organs and how these processes cause disease.
“The average American born today will live nearly 79 years,” said HMS dean Jeffrey Flier in opening remarks. “Along with this gift of longevity will come a crushing burden of disability and chronic illness. Unless we do something to alleviate this burden, healthcare costs could one day bankrupt our economy.” Flier discussed recent advances in understanding the biology and potential interventions, including the discovery of the beneficial effects of resveratrol, a compound found in plants.
“We’re not aiming to fill nursing homes,” confirmed Paul Glenn, whose foundation funds aging research labs at Harvard, MIT, and the Salk Institute in San Diego.
For most cancers, advancing age is the most important risk factor, said Ronald DePinho, HMS professor of medicine (genetics) at the Dana-Farber Cancer Institute. Age-related shortening of the telomeres, structures that cap the end of chromosomes, can make the chromosome unstable with catastrophic effects. Dysfunctional telomeres can prompt damaged cells to grow into tumors, a process that may be reversible, based on studies in mice, said DePinho, the first of nine scientists who spoke.
Aging is also the major risk factor for neurodegeneration, said Bruce Yankner, HMS professor of pathology and co-director of the Paul F. Glenn Laboratories for Biological Mechanisms of Aging. Neuronal loss does not account for much of the change in the normal aging brain, he said. Rather, there sees to be a progressive silencing of genes. In the brains of people who died with Alzheimer’s disease, Yankner and his colleagues have found an early onset to the downregulation of genes for GABA, a neurotransmitter associated with learning and memory, and those genes showed 10-fold greater DNA damage.
The aging of hematopoietic stem cells may contribute to reduced immune function with age and may contribute to cancer, said Stanford University stem cell researcher Irving Weissman. In cancer, Weissman reported, the “don’t eat me” signal on the surface of leukemia stem cells can be effectively blocked by antibodies, which clears the cancer in mice.
