Abstract
It is known that stress alters homeostasis and may lead to accelerated aging. However, little is known about the contribution of innate susceptibility to stress to the deterioration of physiological functions, acceleration of aging and developing of age-related diseases. By using socially-submissive stress susceptible (Sub) and socially-dominant stress resilient (Dom) selectively bred mouse model we observed a marked reduction in the lifespan of both male and female Sub mice. We found that innate susceptibility to stress correlates with chronic inflammation, development of splenomegaly and a significant increase in the levels of circulating pro-inflammatory cytokines IL-1β and IL-6. Furthermore, Sub mice showed a marked hypoglycemia, reduction of insulin levels, increase in GSK3 activity and elevation of IGF-1 serum levels, as well as low skin surface temperature and body weight. Interestingly, lifelong exposure of Sub mice to chronic mild stress did not further reduce their lifespan, indicating a high level of intrinsic stress. Taken together, our data reveal that social submissiveness coupled with innate stress sensitivity coincides with inflammation, leading to the deterioration of physiological functions and early aging independent of whether an individual is exposed to stress or not.
Highlights
Biological aging is defined by a progressive and generalized impairment of physiological functions, which results in a decreased adaptive capacity, a reduced resistance to harmful environmental factors and an increased threat of disease acquisition
Our data reveal that social submissiveness coupled with innate stress sensitivity coincides with inflammation, leading to the deterioration of physiological functions and early aging independent of whether an individual is exposed to stress or not
The analysis of the Kaplan-Meier survival curves showed that the lifespan of the dominant stress resilient (Dom) animals was significantly longer than that of the Sub animals
Summary
Biological aging is defined by a progressive and generalized impairment of physiological functions, which results in a decreased adaptive capacity, a reduced resistance to harmful environmental factors and an increased threat of disease acquisition. External factors contribute to the deterioration of physiological functions and even accelerate the rate of aging. Animal studies have shown that social defeat affects physiological parameters, leading to alterations in social behavior, anhedonia, changes in drug preference and disease susceptibility [3,4,5]. It has been demonstrated that social stress has a much stronger impact on animal physiology and behavior than normally used stressors such as restraint, electric shock, and chronic mild stress [6]. It has been shown that life-long social defeat significantly affects survival [7]
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