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Longevity factor klotho and chronic psychological stress.

Prather AA, Epel ES, Arenander J, Broestl L, Garay BI, Wang D, Dubal DB - Transl Psychiatry (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Lower klotho levels are associated with clinically significant depressive symptoms in chronically high-stress women. (a) In all women assessed (n=178), serum klotho levels decreased as a function of higher depressive symptom score (Inventory of Depressive Symptomatology (IDS); r=−0.20, P=0.007), an association that remained significant after adjusting for age and body mass index (BMI; B=−0.17, P=0.026; ΔR2=0.02) (b). Women under high chronic stress and experiencing moderate to severe depression (Inventory of Depressive Symptomatology (IDS) ⩾26, n=19) had significantly lower levels of klotho compared with women under low stress without depression (IDS 0–12, n=57; F(2,99)=4.26, P=0.017; pairwise comparison, **P=0.008). In women without depression, post hoc comparisons also indicated a trend for lower klotho levels in high-stress women (n=26) compared with low-stress women (#P=0.079). Analyses were carried out on log10-transformed klotho values. Data are means±s.e.m.
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fig3: Lower klotho levels are associated with clinically significant depressive symptoms in chronically high-stress women. (a) In all women assessed (n=178), serum klotho levels decreased as a function of higher depressive symptom score (Inventory of Depressive Symptomatology (IDS); r=−0.20, P=0.007), an association that remained significant after adjusting for age and body mass index (BMI; B=−0.17, P=0.026; ΔR2=0.02) (b). Women under high chronic stress and experiencing moderate to severe depression (Inventory of Depressive Symptomatology (IDS) ⩾26, n=19) had significantly lower levels of klotho compared with women under low stress without depression (IDS 0–12, n=57; F(2,99)=4.26, P=0.017; pairwise comparison, **P=0.008). In women without depression, post hoc comparisons also indicated a trend for lower klotho levels in high-stress women (n=26) compared with low-stress women (#P=0.079). Analyses were carried out on log10-transformed klotho values. Data are means±s.e.m.

Mentions: We next determined whether lower levels of klotho were linked with depressive symptoms, a prominent neural correlate of chronic psychological stress.45 We found that in all women assessed, lower klotho associated with higher depressive symptoms (r=−0.20, P=0.007), an association that remained significant after adjusting for age and BMI (B=−0.17, P=0.026; ΔR2=0.02; Figure 3a). Because high-stress caregivers experience more depression, we explored whether the combination of being a high-stress caregiver and reporting high depressive symptoms (Inventory of Depressive Symptomatology scores in the moderate and above range ⩾26) had lower levels of klotho compared with high-stress caregivers and low-stress controls who reported minimal levels of depressive symptoms (Inventory of Depressive Symptomatology scores: 0–13). High-stress women with moderate to severe, but not mild, depressive symptoms had significantly lower levels of klotho compared with low-stress women without depression (P=0.008; Figure 3b). This statistical difference remained significant after adjusting for age and BMI. In women without depression, there was a trend toward lower levels of klotho in high-stress women compared with low-stress women (P=0.079). Thus, depression was linked with lower klotho levels, particularly in high-stress women with moderate to severe depressive symptoms.


Longevity factor klotho and chronic psychological stress.

Prather AA, Epel ES, Arenander J, Broestl L, Garay BI, Wang D, Dubal DB - Transl Psychiatry (2015)

Lower klotho levels are associated with clinically significant depressive symptoms in chronically high-stress women. (a) In all women assessed (n=178), serum klotho levels decreased as a function of higher depressive symptom score (Inventory of Depressive Symptomatology (IDS); r=−0.20, P=0.007), an association that remained significant after adjusting for age and body mass index (BMI; B=−0.17, P=0.026; ΔR2=0.02) (b). Women under high chronic stress and experiencing moderate to severe depression (Inventory of Depressive Symptomatology (IDS) ⩾26, n=19) had significantly lower levels of klotho compared with women under low stress without depression (IDS 0–12, n=57; F(2,99)=4.26, P=0.017; pairwise comparison, **P=0.008). In women without depression, post hoc comparisons also indicated a trend for lower klotho levels in high-stress women (n=26) compared with low-stress women (#P=0.079). Analyses were carried out on log10-transformed klotho values. Data are means±s.e.m.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4490291&req=5

fig3: Lower klotho levels are associated with clinically significant depressive symptoms in chronically high-stress women. (a) In all women assessed (n=178), serum klotho levels decreased as a function of higher depressive symptom score (Inventory of Depressive Symptomatology (IDS); r=−0.20, P=0.007), an association that remained significant after adjusting for age and body mass index (BMI; B=−0.17, P=0.026; ΔR2=0.02) (b). Women under high chronic stress and experiencing moderate to severe depression (Inventory of Depressive Symptomatology (IDS) ⩾26, n=19) had significantly lower levels of klotho compared with women under low stress without depression (IDS 0–12, n=57; F(2,99)=4.26, P=0.017; pairwise comparison, **P=0.008). In women without depression, post hoc comparisons also indicated a trend for lower klotho levels in high-stress women (n=26) compared with low-stress women (#P=0.079). Analyses were carried out on log10-transformed klotho values. Data are means±s.e.m.
Mentions: We next determined whether lower levels of klotho were linked with depressive symptoms, a prominent neural correlate of chronic psychological stress.45 We found that in all women assessed, lower klotho associated with higher depressive symptoms (r=−0.20, P=0.007), an association that remained significant after adjusting for age and BMI (B=−0.17, P=0.026; ΔR2=0.02; Figure 3a). Because high-stress caregivers experience more depression, we explored whether the combination of being a high-stress caregiver and reporting high depressive symptoms (Inventory of Depressive Symptomatology scores in the moderate and above range ⩾26) had lower levels of klotho compared with high-stress caregivers and low-stress controls who reported minimal levels of depressive symptoms (Inventory of Depressive Symptomatology scores: 0–13). High-stress women with moderate to severe, but not mild, depressive symptoms had significantly lower levels of klotho compared with low-stress women without depression (P=0.008; Figure 3b). This statistical difference remained significant after adjusting for age and BMI. In women without depression, there was a trend toward lower levels of klotho in high-stress women compared with low-stress women (P=0.079). Thus, depression was linked with lower klotho levels, particularly in high-stress women with moderate to severe depressive symptoms.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.

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.

No MeSH data available.


Related in: MedlinePlus