Abstract
Chronic psychological stress is associated with accelerated aging and premature morbidity and mortality; however, the biology linking chronic psychological stress and its maladaptive effects remains largely unknown. Klotho is a pleiotropic hormone that regulates the aging process and promotes better brain and body health. Whether klotho is linked to psychosocial stress or its negative impact in humans has not been investigated. To address this gap, we recruited 178 healthy women who were either chronically high-stress maternal caregivers for a child with autism spectrum disorder (n=90) or low-stress control mothers of a typically developing child (n=88). We found that women under high chronic stress displayed significantly lower levels of the longevity hormone klotho compared with low-stress controls (t(176)=2.92, P=0.004; d=0.44), and the decrease among those under high stress was age-dependent. In addition, high-stress caregivers who reported more depressive symptoms displayed even lower klotho levels compared with low-stress participants. These findings provide the first evidence that klotho levels are sensitive to psychosocial stressors and raise the possibility that klotho may serve as a novel biological link connecting stress, depression and risk for accelerated disease development. Furthermore, these findings have important implications for understanding the plasticity of the aging process and may represent a therapeutic target for mitigating the deleterious effects of chronic psychological stress on health and well-being.
Highlights
Improvements in medical care over the past century have enabled people to live longer than in any time in human history
We hypothesized that women under chronic stress would display lower levels of klotho compared with low-stress, age-matched controls, and that these differences would be greater in women concurrently reporting greater depressive symptomatology
As chronic psychological stress is associated with accelerated biological aging,[44,46,47] we explored whether age-related decline in klotho occurs more rapidly under high stress
Summary
Improvements in medical care over the past century have enabled people to live longer than in any time in human history. Higher serum klotho levels prospectively predict better daily functioning (that is, activites of daily living) and lower mortality risk in older adults (aged 65 and older), independent of age, sex, body mass index (BMI), education and health status.[27,28] Despite the potential of klotho as a marker of biological aging, there is no research to date examining whether klotho levels relate to psychosocial factors (for example, chronic stress) well known to predict elevations in age-related disease risk Chronic psychological stress, such as the stress conferred by serving as a caregiver to a spouse with dementia or a child with a chronic illness, has consistently been associated with accelerated age-related disease and onset of psychiatric illness,[29] major depression.[30] A large literature demonstrates that chronically stressed caregivers report higher levels of distress and depressive symptoms and suffer more health problems, including cardiometabolic conditions[31,32] and premature mortality,[33,34] compared with non-caregivers (reviewed in Pinquart and Sorensen[29] and Vitaliano et al.[35]). We hypothesized that women under chronic stress would display lower levels of klotho compared with low-stress, age-matched controls, and that these differences would be greater in women concurrently reporting greater depressive symptomatology
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