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Review
. 2012 Dec;34(6):1421-33.
doi: 10.1007/s11357-011-9319-0. Epub 2011 Oct 5.

Psychological stress and aging: role of glucocorticoids (GCs)

K M Mehedi Hasan  1 , Md Shaifur Rahman, K M T Arif, Mahbub E Sobhani
Affiliations
Review

Psychological stress and aging: role of glucocorticoids (GCs)

K M Mehedi Hasan et al. Age (Dordr). 2012 Dec.

Abstract

Psychological stress has extreme adverse consequences on health. However, the molecular mechanisms that mediate and accelerate the process of aging due to stress hormone are not well defined. This review has focused on diverse molecular paths that come out in response to chronic psychological stress via releasing of excessive glucocorticoids (GCs), involved in the aging process. GCs suppress transcription of nuclear cell adhesion molecules which impair synaptic plasticity, memory formation, and cognitive ability. Again, GCs promote muscle atrophy by means of motivating ubiquitin proteasome system and can repress muscle protein synthesis by inhibition of PI3-kinase/Akt pathway. GCs also inhibit interleukin-2 synthesis through suppressing T cell receptor signal that leads to loss of T cell activation, proliferation, and B-cell activation. Moreover, GCs increase the expression of collagenase-3, RANK ligand, and colony stimulating factor-1 that induce bone resorption. In general, stress-induced GCs can play causal role for aging and age-related disorders.

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Figures

Fig. 1
Fig. 1
Suppression of NCAM expression by GCs. GCs triggers (+) GR to active state which negatively (−) regulated NF-κB and AP-1, consequently blocking (X) NCAM gene expression instead of normal membrane receptor mediated signaling pathways
Fig. 2
Fig. 2
Mechanism of immunosuppression of T cell activation by GCs. Schematic representation of TCR signaling process subdivided into two sides. Left sides present normal signaling through which IL-2 gene expressed. But, on right sides it is seen that GRs mediated TCR signaling where the intracellular membrane signal complex is negatively (−) regulated and consequently the tuned innermembrenal complex loosening their relation results in TCR signal impairment, through this IL-2 gene expression is retarded (X)
Fig. 3
Fig. 3
Mechanism of muscle protein synthesis inhibition by GCs. Generally PI3K phosphorylates phosphatidylinositol 4, 5-bisphosphate (PIP2) to PIP3 which follow the Akt/PKB pathways for protein synthesis. But stress induced activated GRs negatively (−) regulate PI3K and block (X) the phosphorylation of PIP2. Consequently, the normal pathway falls down and depletion of protein synthesis
Fig. 4
Fig. 4
Protein degradation via UPS by GCs. Activated GRs positively (+) regulates and increases the activity of calpain, E2, E3 and 26S proteosome. As a results muscle proteins are degraded and ultimately fallout in muscle atrophy
Fig. 5
Fig. 5
Mechanism of GCs induced osteoporosis. The illustration represents two ways viz. bone resorption and bone matrix break down as a process for osteoporosis. Here, activated GRs positively (+) regulated MMP-13 and increased ejection of collagenase 3 which is responsible for bone matrix break down. On the other side, RANKL and MCSF positively (+) regulated and OPG is negatively (−) regulated by GRs. The both regulation induce bone resorption
Fig. 6
Fig. 6
An overview of the role of chronic psychological stress leading to aging
See this image and copyright information in PMC

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