Emotional stress and aging

Abstract

Senescence is that phase of the life span that is associated with an increasing probability of dying. A fundamental feature of senescence is "the diminished ability to maintain homeostasis".Stress is any real (physical.) or imagined (psychological and/or emotional) threatening situation, in which cellular hoincostasis is disturbed. In humans, mental or physical tension or strain, urgency, pressure, anxiety are conditions associated with stress. Physical or psychological stressors produce responses via the same cascade. Acute stress responses (the first wave) are immediate motor and cognitive responses. Chronic or prolonged stress responses (the second wave) are more delayed neuroendocrine responses. In humans, glucocorticoids (GCs); mainly cortisol increase to stress levels in the second wave, which is particularly responsible from the neuroendocrine effects.GCs have two types of receptors: Type I, mineralocorticoid receptor (MR, high affinity-low capacity) and Type II, glucocorticoid receptor (GR, low affinity-high capacity). MRs may play a role in regulating circadian changes in corticosteroid production. They regulate stress responses by negative feedback inhibition (NFBI) of the HPA-axis under physiological or basal conditions. Whereas, GRs become occupied during chronic stress and when there is excess release of GCs.The deleterious effects of GCs in the nervous system mainly are; disruption of learning, memory and plasticity (and cognition), inhibition of dentate neurogenesis, atrophy of the neuronal processes, endangerment of hippocampal neurones and neurotoxicity. GC exposure (i.e. basal concentrations) begin to increase somewhat linearly from late middle ages. "The feed-forward cascade" can partly explain the reason of this increase. Hippocampus is a negative feedback mediator of GC secretion. This is accomplished via hippocampal inhibitory projections to CRH neurones in the hypothalamus. Thus, hippocampal damage and down regulation of hippocampal GRs cause transient GC hypersecretion. Therefore, rising of basal levels of GCs and hippocampal neurone loss occur. So, impaired feedback mechanisms at the level of GRs contribute to "the hyperactivation of the HPA axis" with age. As a result clinically common findings of aging in humans at present can be summarised as following (note that, there are individual variations):1- Decline in cognitive vitality and learning and memory disorders2- Laboratory findings (without an existence of other medical comorbidities): a) Increase in the basal levels of HPA axis hormones: GCs (mainly cortisol), ACTH and CRH and b) Resistance to suppression tests.3- MRI (magnetic resonance imaging): Hippocampal atrophy and volume loss4- Histological findings (Practically not possible, only in biopsy specimens or in post-mortem analysis): Dendritic atrophy, Tau protein inclusions, and. neurone loss.So it can be concluded taht, "if we are sorry or make stress because of aging we must be aware of the danger that we may enhance the aging processes more".