Mechanisms of chronic stress-induced aging-associated diseases.
The extraordinary extension of human lifespan over the past five generations has exponentially increased the prevalence of a myriad of aging-associated chronic diseases, including heart failure, atherosclerosis, osteoarthritis, Alzheimer`s disease (AD) and AD-related dementias (AD/ADRD), chronic kidney disease,glaucoma, osteoporosis, and pulmonary fibrosis. Epidemiological and clinical studies suggest that prolonged life stress, low socio-economic status (SES) and health disparity exacerbate aging-associated diseases and increase mortality rate in humans and animal models. However how remains poorly established.
We developed a unique mouse model of chronic psychosocial stress [1,2]. Briefly stable resident/intruder pairs of adult male mice are established after a baseline period. In the stress phase resident/intruder pairs live in the same cage separated by a perforated partition, which allows sensory but not physical contact and are allowed a brief daily physical interaction which lasted a maximum of 10 min. Subordinate and dominant mice are identified by direct observation. 
We demonstrated that subordinate mice (mice having low social rank) manifest acomplex syndrome characterized by a depression-like behavior, increasedanxiety, neuroimmune and neuroendocrine abnormalities as well as vulnerabilityto diet induced obesity [3-7].
Recent work from our lab also established that chronic stress is a novel physiological stimulus promoting the recruitment and activation of the brown adipose tissue in mouse housed at thermoneutrality, thereby exerting an anti obesity effect [7].
Another recent project established for the first time that lifelong chronic psychosocial stress shortens lifespan in subordinate mice, and is associated with earlier onset of aging-associated diseases including atherosclerosis as well as with an increase in molecular markers of cellular senescence [8].
Ongoing projects:
The mechanism of stress-induced accumulation of senescent cells.
The long term consequences of chronic social stress on mortality and disease of ageing.
Stress-induced exacerbation of genetic and environmentally-induced cardiometabolic and neuromuscular diseases.
References:1. Bartolomucci A,et al. Physiol Behav. 2001. 2. Bartolomucci et al., NeurosciBiobehav Rev. 2005. 3. Sanghez et al.,Psychoneuroendocrinology 2013. 4. Sanghez et al., Stress, 2016. 5. Razzoli et al.,Mol Metabol 2016. 6. Razzoli et al., Front Nutr 2015. 7. Razzoli et al., Mol Metabol 2016. 7. Razzoli et al., Aging Cell 2018.
Recent review papers:
Stress, overeating, and obesity: Insights from human studies and pre-clinical models.
The Dichotomous Effect of Chronic Stress on Obesity.
Stress revisited: a critical evaluation of the stress concept.
Supported by NIH/NIA R01AG043972, Minnesota Partnership for Biotechnology and Medical Genomics, Summer`s Wish Fund, Greg Marzolf Jr.Foundation Research Grant, Center on Aging, Wallin Neuroscience Discovery Fund.
