An analysis of UK Biobank data showed that risks of depression and anxiety increase with biological age, i.e., the physiological condition of an individual’s body. Biological age assessment in this study was based on a number of clinical traits and biomarkers using the Klemera-Doubal method and the PhenoAge algorithm. The study was published in Nature Communications.
Aging is a complex biological process. After a certain point in one’s lifetime, the resilience and integrity of cells, tissues and organs starts to degrade. To assess this process of degradation, scientists have developed the concept of biological age. While calendar age is simply the number of years since a person was born, biological age is based on assessments of the physiological condition of an individuals’ body.
It takes into account factors such as overall health, physical fitness, genetic influences, lifestyle choices and environmental factors. It reflects how well the body is functioning relative to its calendar age.
Scientists have proposed various methods to measure biological age. These range from individual biomarkers, such as telomere length, to complex algorithms that integrate information from various sources and levels of analysis to produce an assessment. Telomeres are repetitive sequences of DNA located at the end of chromosomes in cells. Each time a cell divides they become shorter.
In this way they can be regarded as a biological clock showing the ageing process. If telomeres become too short, cells may reach a state called replicative senescence, unable to divide any more, and undergo programmed cell death. However, they are not the only indicator of biological aging.
Study author Xu Gao and his colleagues wanted to examine how the risk of depression and anxiety changes with biological age. Depression and anxiety are common mental health disorders that often develop together, particularly in older adults. Studies have been unclear in their conclusions about whether poor mental health accelerates processes of biological aging or accelerated biological aging increases the risk of developing depression and anxiety disorders.
The researchers analyzed data from the UK Biobank study, an ongoing prospective study with over 500,000 participants who were recruited back in 2006-2010 when they were between 37 and 73 years old. At the start of the study, participants provided data about their lifestyle and health. Biological samples were collected. Additional data from these participants was collected on multiple occasions across the years. This included mental health information.
The researchers excluded from their analysis participants who already suffered from depression or anxiety at the start of the study (54,554 participants) and calculated the association between biological age and the incidence of depression or anxiety on the remaining participants. Since mental health information was not available for all the participants, the final dataset for this analysis consisted of 369,745 individuals.
Depression and anxiety were assessed using hospital admission records linked to the participants’ data in the UK Biobank dataset and mental health questionnaires that were administered at the start of the study (the Patient Health Questionnaire-4). Biological age was assessed using the Klemera-Doubal method and the PhenoAge algorithm.
Results showed that participants with older biological age had higher scores on the depression and anxiety measure. They were also more likely to have a diagnosis of depression and anxiety at the start of the study compared to participants of the same calendar age who were biologically younger.
Taking into account socioeconomic factors, health behaviors and chronic diseases made this association weaker, but it was still present. The association was confirmed with both methods of calculating biological age. The association with biological age was stronger for depression than for anxiety. Participants’ genetic risk for depression and anxiety was found to be independent of biological age. When genetic risk was taken into account the association with biological age remained.
“We tested associations of blood-chemistry measures of biological aging with prevalent and incident depression and anxiety among a half-million midlife and older adults in the UK Biobank. The main findings were that adults with more advanced biological age were more likely to experience depression and anxiety at baseline and were at higher risk of depression/anxiety over eight years of follow-up, as compared with peers who were the same chronological age, but who were tested to be biologically younger,” the study authors concluded.
“The risk associated with biological age was independent of and additive to genetic risk measured using a polygenic risk score [a numerical score that estimates an individual’s genetic risk or predisposition for a particular trait or disease based on multiple genetic variants across the genome]. The risk was also independent of self-reported history of childhood adversity.”
The study makes an important contribution to understanding the biological basis of anxiety and depression. However, it also has limitations that need to be taken into account. Notably, the study is observational. This means that possibilities to draw cause-and-effect conclusions from it are limited.
The possibility that both biological aging and the risk of depression and anxiety are caused by third factors not taken into account in the study cannot be excluded. Additionally, study participants were volunteers, more or less self-selected for the study. Results on a more representative sample might not be the same.
The study, “Accelerated biological aging and risk of depression and anxiety: evidence from 424,299 UK Biobank participants”, was authored by Xu Gao, Tong Geng, Meijie Jiang, Ninghao Huang, Yinan Zheng, Daniel W. Belsky, and Tao Huang.
