Depression gets old fast: do stress and depression accelerate cell aging?

Wolkowitz, Owen M.; Epel, Elissa S.; Reus, Victor I.; Mellon, Synthia H.

doi:10.1002/da.20686

Cited by 272 publications

(226 citation statements)

References 214 publications

(293 reference statements)

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“…53-54 So extended disease- and/or age-related exposure to elevated glucocorticoid levels could contribute to a series of physiological changes akin to an accelerated aging process. 55 Interestingly, the hippocampus is the not the only node in the mood network that undergoes structural remodeling as a result of stress-related HPA axis dysfunction. The prefrontal cortex atrophies and the amygdala increases in size during acute stress and atrophies during extended periods of stress, thus suggesting multiple routes by which stress can disrupt the mood network.…”

Section: Current Hypotheses For Biological Mechanisms Promoting Lldmentioning

confidence: 99%

The Age-by-Disease Interaction Hypothesis of Late-Life Depression

McKinney

Sibille

2013

The American Journal of Geriatric Psychiatry

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The phenomenological diagnosis of depression is successful in increasing diagnostic reliability, but it is a classification scheme without biological bases. One subtype of depression for which evidence suggests a unique biological basis is late-life depression (LLD), with first onset of symptoms after the age of 65. LLD is common and poses a significant burden on affected individuals, caretakers, and society. The pathophysiology of LLD includes disruptions of the neural network underlying mood, which can be conceptualized as the result of dysfunction in multiple underlying biological processes. Here, we briefly review current LLD hypotheses and then describe the characteristics of molecular brain aging and their overlap with disease processes. Further, we propose a new hypothesis for LLD, the Age-by-Disease Interaction hypothesis, which posits that the clinical presentation of LLD is the integrated output of specific biological processes that are pushed in LLD-promoting directions by changes in gene expression naturally occurring during brain aging, hence leading the brain to a physiological state that is more susceptible to LLD, since additional pushes by genetic, environmental and biochemical factors may now be sufficient to generate dysfunctional states that produce depressive symptoms. We put our propositions together into a decanalization model to aid in illustrating how age-related biological changes of the brain can shift the repertoire of available functional states in a pro-depression direction, and how additional factors can readily lead the system into distinct and stable maladaptive phenotypes, including LLD. This model brings together basic research on neuropsychiatric and neurodegenerative diseases more closely with the investigation of normal aging. Specifically, identifying biological processes affected during normal aging may inform the development of new interventions for the prevention and treatment of LLD.

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Section: Current Hypotheses For Biological Mechanisms Promoting Lldmentioning

confidence: 99%

The Age-by-Disease Interaction Hypothesis of Late-Life Depression

McKinney

Sibille

2013

The American Journal of Geriatric Psychiatry

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“…12 Glucocorticoids have been demonstrated to downregulate telomerase activity and accelerate senescence. 13,14 Elevated levels of endogenous GC were observed in age and estrogen depletion states associated with low populations and capabilities of MSC and accelerated senescence of MSC. 15,16 Collectively, this previous evidence strongly indicated that natural physiological endogenous GC may cause MSC to lose stem cell characteristics in terms of self-renewal and multiple differentiations and hasten their senescence.…”

Section: Introductionmentioning

confidence: 99%

Effects of Glucocorticoid Receptor Small Interfering RNA Delivered Using Poly Lactic-Co-Glycolic Acid Microparticles on Proliferation and Differentiation Capabilities of Human Mesenchymal Stromal Cells

Hong

Wei

Joshi

et al. 2012

Tissue Engineering Part A

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Bone marrow-derived mesenchymal stem cells (MSC) are a potential attractive source of cells for stem cellbased tissue regeneration, but the small number and reduced capabilities of MSC proliferation and differentiation due to in vitro replicative senescence and donor-associated pathophysiological factors, including age and estrogen depletion, severely restrict their potential usefulness in clinical applications. Glucocorticoids (GC) are well-known steroid hormones that regulate MSC proliferation and differentiation, but the defined effects and underlying mechanisms of endogenous glucocorticoids on MSC characteristics are not understood. This study investigated the effects of the blockage of endogenous GC using glucocorticoid receptor (GR) small interfering RNA (siRNA) delivered using biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles on proliferation and differentiation capabilities of human MSC in vitro. The results show that we can prepare PLGA microparticles as a delivery system for GR siRNA and maintain release of siRNA up to 40 days in vitro. Transfection of GR siRNA significantly downregulates GR and upregulates the expression of fibroblast growth factor-2 and Sox-11 of human MSC. MSC that have proliferated with endogenous GC blocked in vitro have greater proliferation rates and exhibit upregulated expression of osteogenic markers (alkaline phosphatase and core binding factor alpha 1) under differentiation stimulation after 1 week. Under adipogenic differentiation, MSC proliferated in vitro with siRNA transfection, resulting in significantly lower adipogenic markers (peroxisome proliferatoractivated receptor and lipoprotein lipase) than controls. In conclusion, PLGA particles can serve as a tool for delivery of GR siRNA to effectively block the effects of endogenous GC on MSC, which has the potential to improve the capabilities of human MSC for clinical application by preventing replicative senescence.

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“…These points to the possibility that a lower behavioral tendency in cultivating social ties may accentuate cortisol secretion and decelerate diurnal decline, which in turn promotes ill health and maladjustment in the elderly. Given that aging is associated with an elevated cortisol secretion (e.g., [30]) and the linkage between overproduction of this hormone and depression in the elderly (e.g., [31]), a lower motivation in network cultivation may exacerbate hypercortisolism in old age and leads to increased morbidity. Further research is warranted to illuminate the mechanisms whereby this specific psychosocial variable is translated into health outcomes in the aging populations.…”

Section: Social Network Cultivation and Diurnal Cortisol Profiles In mentioning

confidence: 99%

Social Network Cultivation and Diurnal Cortisol Profiles in Healthy Chinese Elders

Lai¹,

Evans²,

Chong³

2017

Neuropsychiatry

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Objective:Psychobiological research on aging in humans is confounded by individual differences that remain to be characterized more precisely. The present study was designed to address this issue by examining the impact of Network Cultivation, a behavioral tendency to strengthen one's social ties on diurnal cortisol profiles in healthy Chinese elders in Hong Kong. Methods:Authors performed secondary analysis of data reported by Lai [1] using multilevel modelling. Seventy-eight healthy seniors provided saliva samples over two consecutive days at immediately, 3, 6, 9, and 12 hours after waking. Cortisol levels were assayed by using an enzyme-linked immunosorbent assay kit (ELISA) developed for use in saliva. Social network cultivation was measured with the Cultivation subscale of the Support Network Scale (SNS) that had been validated in prior studies with Chinese participants. The relationship between network cultivation and diurnal cortisol rhythms was examined using a mixed effect model. Results:Cortisol levels declined significantly from waking to 12 hours thereafter and the rate of decline decreased significantly over time. In comparison to socially proactive participants, those having lower scores in Network Cultivation exhibited a higher diurnal cortisol level and a less efficient or flatter decline. The effect of Network Cultivation remained significant after controlling the influences of gender, age, waking time, and socioeconomic status. Conclusions:An attenuated behavioural tendency in cultivating social ties in the elders is associated with a higher cortisol level and a flatter diurnal decline, which may increase susceptibility to agerelated diseases. Further research is warranted to uncover the psychophysiological mechanisms translating social network cultivation into altered functioning of the hypothalamic-pituitaryadrenocortical axis.

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Depression gets old fast: do stress and depression accelerate cell aging?

Cited by 272 publications

References 214 publications

The Age-by-Disease Interaction Hypothesis of Late-Life Depression

The Age-by-Disease Interaction Hypothesis of Late-Life Depression

Effects of Glucocorticoid Receptor Small Interfering RNA Delivered Using Poly Lactic-Co-Glycolic Acid Microparticles on Proliferation and Differentiation Capabilities of Human Mesenchymal Stromal Cells

Social Network Cultivation and Diurnal Cortisol Profiles in Healthy Chinese Elders

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