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Jan 4, 2013

Gene Variant Might Lead to a Longer Life

  • Scientists report that a variant of a gene associated with active personality traits in humans seems to also be involved with living a longer life. This derivative of a dopamine-receptor gene—called the DRD4 7R allele—appears in significantly higher rates in people more than 90 years old and is linked to lifespan increases in mouse studies.

    Robert Moyzis, Ph.D., professor of biological chemistry at UC Irvine, and Nora Volkow, M.D., a psychiatrist who conducts research at the Brookhaven National Laboratory and also directs the National Institute on Drug Abuse, led an investigation that included data from the UC Irvine-led 90+ Study in Laguna Woods, CA. Results appear online in The Journal of Neuroscience.

    The variant gene is part of the dopamine system, which facilitates the transmission of signals among neurons and plays a major role in the brain network responsible for attention and reward-driven learning. The DRD4 7R allele blunts dopamine signaling, which enhances individuals’ reactivity to their environment, noted the researchers.

    According to Dr. Moyzis, variation in the number of tandem repeats in the DRD4 region have been tied to “variations in activity levels, stress resilience, and risks of substance abuse and attention deficit hyperactivity disorder.” The research team discovered that a group of people in the 90–109 age range had a statistically higher chance of having a 7-repeat DRD4 allele than an ethnically matched, younger sample of individuals. The scientists postulated that the allele leads to greater longevity. They also noted that the “increased frequency was significant at the genome-wide level only in females, perhaps because early allelic effects are more likely to affect men adversely.”

    “While the genetic variant may not directly influence longevity,” explained Dr. Moyzis, “it is associated with personality traits that have been shown to be important for living a longer, healthier life. It’s been well documented that the more you’re involved with social and physical activities, the more likely you’ll live longer. It could be as simple as that.”

    Numerous studies, he continued, including a number from the 90+ Study, have confirmed that being active is important for successful aging, and it may deter the advancement of neurodegenerative diseases such as Alzheimer’s, said Dr. Moyzis.

    Prior molecular evolutionary research led by Dr. Moyzis and Chuansheng Chen, Ph.D., UC Irvine professor of psychology & social behavior, indicated that this “longevity allele” was selected for during the nomadic out-of-Africa human exodus more than 30,000 years ago.

    In the new study, the UC Irvine team analyzed genetic samples from 310 participants in the 90+ Study. This “oldest-old” population had a 66% increase in individuals carrying the variant relative to a control group of 2,902 people between the ages of 7 and 45. The presence of the variant also was strongly correlated with higher levels of physical activity.

    Next, Dr. Volkow and colleagues at the Brookhaven National Lab found that mice without the variant had a 7% to 9.7% decrease in lifespan compared with those possessing the gene, even when raised in an enriched environment.

    While it’s evident that the variant can contribute to longevity, Dr. Moyzis said further studies must take place to identify any immediate clinical benefits from the research. “However, it is clear that individuals with this gene variant are already more likely to be responding to the well-known medical adage to get more physical activity,” he added.


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