Premature aging in the brain from interaction between Klotho and PTSD

Premature aging in the brain from interaction between Klotho and PTSD

Genetics and the environment (including psychiatric stress) may contribute to the pace of cellular aging, causing some individuals to have a biological age that exceeds their chronological age.

Researchers now have found that a variant in the klotho gene, a gene previously associated with longevity, interacts with post-traumatic stress disorder (PTSD) to predict accelerated aging in brain tissue. These same researchers had previously shown this effect in living subjects when epigenetic age (biological age) was measured in blood, but this is the first time it has been studied in brain tissue.

Using data from individuals who donated their brains, the researchers were able to examine how genetic variation and PTSD status interacted with each other to predict biological age and gene expression. They found that older adults with PTSD showed evidence of accelerated epigenetic aging in brain tissue if they had the "at risk" (variant) at a particular location in the klotho gene. Follow-up molecular experiments showed that this variant regulated the transcription of the klotho gene, suggesting functional consequences of the genetic variant.

The authors found that rs9315202 interacted with PTSD to predict advanced epigenetic age in motor cortex among the subset of relatively older (>=45 years), white non-Hispanic decedents. An evaluation of 211 additional common KL variants revealed that only variants in linkage disequilibrium with rs9315202 showed similarly high levels of significance. 


Both PTSD and klotho impact inflammation, cardiometabolic conditions and neurodegeneration, including Alzheimer's disease. According to the researchers, better understanding how klotho and PTSD interact and the mechanisms linking both genes and traumatic stress to age-related health conditions is important for the development of novel therapeutics.

"This work allows us to better pinpoint who is at risk for accelerated cellular aging, and possibly, premature disease onset (such as neurodegeneration). This can help to identify the populations at greatest risk so that targeted treatments can be matched to the individuals who need it most. As well, the results point to potential therapeutic targets (klotho) in the development of pharmacological approaches to slow the pace of cellular aging," adds lead author.

These findings appear in the journal Neuropsychopharmacology.

https://www-nature-com-443.webvpn.jnu.edu.cn/articles/s41386-020-00884-5

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