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March 5, 2008

Researchers Implicate Gene Mutations in Human Longevity

  • Mutations in genes involved in the cell-signaling pathway related to growth seems to also influence human longevity, according to a group of scientists. The research was conducted in Ashkenazi Jews between the ages of 95 and 110 and their children and focused on genes involved in the action of insulin-like growth factor (IGF-I).

    “Our findings suggest that by interfering with IGF-I signaling, these gene mutations somehow play a role in extending the human life span, as they do in many other organisms,” says Dr. Nir Barzilai, senior author of the study and director of the Institute for Aging Research at Albert Einstein College of Medicine of Yeshiva University.

    Animal research had shown that mutations to genes involved in the IGF-I signaling pathway cause two effects: impaired growth and longer life spans. Hence, the Einstein scientists reasoned that altered signaling in this pathway might also influence human longevity.

    To find out, they analyzed IGF-I-related genetic variations in 384 Ashkenazi Jewish centenarians. Since plasma levels of IGF-I do not reflect their levels at a younger age, the researchers also looked at the children of these centenarians. The control group consisted of Ashkenazi Jews the same age as the centenarians’ children but with no family history of longevity.

    The female children of the centenarians had IGF-I plasma levels that were 35% higher than female controls, perhaps a sign that the body was compensating for a glitch in IGF-I signaling by secreting increased amounts of the hormone, the scientists hypothesize. The daughters of centenarians were also found to be 2.5 cm shorter than female controls. The researchers add that the IGF-I cell-surface receptor genes of centenarians and their daughters were much more likely to have a variety of mutations than were the receptor genes of the controls.

    Dr. Barzilai says that a drug that decreases IGF-I action is currently being tested as a cancer treatment and could be useful in delaying aging. “Since the subjects in our study have been exposed to their mutations since conception, it is not clear whether people would need such a therapy throughout life or if it could help people who received it at a later time.”

    Besides the group at Einstein, other researchers were from UCLA’s David Geffen School of Medicine and the Johns Hopkins University School of Medicine. Their findings were described in the March 4 issue of the Proceedings of the National Academy of Sciences.