Stress responses and innate immunity: aging as a contributory factor

Abstract

SummaryEvolutionary pressure has selected individuals with traits that allow them to survive to reproduction, without consideration of the consequences for the post-child rearing years and old age. In the 21st century, society is populated increasingly by the elderly and with the falling birth rate and improved health care this trend is set to continue for the foreseeable future. To minimize the potential burden on health services one would hope that 'growing old gracefully' should also mean 'growing old healthily'. However, for too many the aging process is accompanied by increasing physical and mental frailty producing an elevated risk of physical and psychological stress in old age. Stress is a potent modulator of immune function, which in youth can be compensated for by the presence of an optimal immune response. In the elderly the immune response is blunted as a result of the decline in several components of the immune system (immune senescence) and a shifting to a chronic pro-inflammatory status (the so-called 'inflammaging' effect). We discuss here what is known of the effects of both stress and aging upon the innate immune system, focusing in particular upon the age-related alterations in the hypopituitary-adrenal axis. We propose a double hit model for age and stress in which the age-related increase in the cortisol/sulphated dehydroepiandrosterone ratio synergizes with elevated cortisol during stress to reduce immunity in the elderly significantly.

Cortisol, DHEAS, their ratio and the metabolic syndrome: evidence from the Vietnam Experience Study

“…adipose tissue and immune cells (25). Indeed, our own in vitro data have shown that DHEAS can overcome the suppressive effects of cortisol upon immune cell function, specifically the generation of superoxide by neutrophils (15), supporting the proposal that it is the ratio of these two hormones that will determine biological outcome in vivo (26). Moreover, there are no reports of MetS suppressing DHEAS production, supporting the notion that the direction of causality is from a lower ratio to MetS.…”

The PPAR-γ Agonist, Darglitazone, Restores Acute Inflammatory Responses to Cerebral Hypoxia–Ischemia in the Diabeticob/obMouse

“…It has long been appreciated that the inhibition of leptin signaling that results from the mutations in the ob/ob mice and db/db mice leads to an elevation of CORT levels, which in turn have been linked to the suppression of inflammatory responses (Butcher and Lord, 2004;Fiuza and Suffredini, 2001). Therefore, it is important to note that accompanying the reduced blood glucose and lipid-lowering effect, darglitazone significantly decreased the CORT level in both control and diabetic ob/ob mice after 4 h of H/I recovery, but this effect was lost at later time points of H/I recovery.…”

Macrophage inhibitory cytokine-1 is associated with cognitive impairment and predicts cognitive decline - the Sydney Memory and Aging Study

“…With the increasing evidence that inflammation plays an important role in age-related cognitive decline and dementia, there has been a recent surge in interest in inflammatory biomarkers (Butcher & Lord, 2004). Several studies have found that inflammatory markers, such as interleukin-6 (IL-6), interleukin-12 (IL-12), tumor necrosis factor-a (TNFa), and C-reactive protein (CRP), are elevated in the elderly and are associated with cognitive impairment and decline (Licastro et al, 2000;Engelhart et al, 2004;Dimopoulos et al, 2006;Alvarez et al, 2007;Zuliani et al, 2008;Trollor et al, 2011), as well as increased risk of mortality .…”