Researchers identify gene variant associated with cellular aging

(Boston)–It is well known that psychiatric stress is associated with accelerated aging. Now, a new study shows that a gene mutation interacts with multiple types of psychiatric stress including post-traumatic stress disorder (PTSD), pain and sleep disturbances in association with cellular aging.

The klotho gene, which is named for the Greek Goddess Clotho who “spins the thread of life,” has been connected with longevity and a variety of age-related conditions and diseases. This is the first time it has been shown to be a marker for accelerated cellular aging in humans.

The study involved 309 U.S. military veterans, of which a large percentage experienced PTSD, who had been deployed to the wars in Iraq and/or Afghanistan. All participants gave blood samples for genetic and metabolic analyses, and were evaluated for psychiatric conditions. They also underwent magnetic resonance imaging (MRI) to examine brain structure and function.

The researchers found that those with a particular klotho genotype who also had more severe PTSD symptoms were the ones who showed the strongest evidence of accelerated cellular aging. “We know that stress increases the likelihood of declining health. Our results suggest that klotho could be one factor that coordinates this decline across both the periphery and central nervous system, making individuals with substantial psychiatric stress more vulnerable to its pathological effects,” explained corresponding author Erika J. Wolf, PhD, a clinical research psychologist at the National Center for PTSD at VA Boston Healthcare System.

According to the researchers, this study points to new directions that could be useful for slowing or reversing accelerated aging and thereby stemming the tide of stress- and age-related health decline. “These results help us to understand the pathophysiology of accelerated aging and raise the possibility that klotho could potentially be a new therapeutic target for protecting against age-related inflammation, metabolic dysfunction, and loss of neural integrity,” added Wolf who is also associate professor of psychiatry at Boston University School of Medicine.

The researchers hope to identify the pathophysiology of stress-related accelerated cellular aging and then develop new treatments that target the implicated pathways. They believe this could eventually reverse or slow the pace of cellular aging and reduce the risk for premature onset of age-related health decline in stressed populations.

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These findings appear online in the journal Brain, Behavior, & Immunity.

Funding for this study was provided by the National Institute on Aging [grant number R03AG051877 (EJW)], United States (U.S.) Department of Veterans Affairs Clinical Sciences R&D (CSRD) Service Merit Review Award [grant number I01 CX-001276-01 (EJW)], National Institute of Mental Health [grant number 5T32MH019836-18 (FGM)], National Institute of Mental Health [grant number R21MH102834 (MWM), VA CSR&D Career Development Award [grant number 1 IK2 CX001772-01 (DRS)], and VA BLR&D Merit Award [grant number 1I01BX003477-01 (MWL)]. This work was also supported by a Presidential Early Career Award for Scientists and Engineers (PECASE 2013A) to EJW, as administered by U.S. Department of Veterans Affairs Office of Research and Development and by the Translational Research Center for TBI and Stress Disorders (TRACTS), a VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B9254-C), and the Cooperative Studies Program, Department of Veterans Affairs. This research is the result of work supported with resources and the use of facilities at the Pharmacogenomics Analysis Laboratory, Research and Development Service, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, and the National Center for PTSD.