The interactive effects of psychosocial stress and diet composition on health in primates

Abstract

Social disadvantage and diet composition independently impact myriad dimensions of health. They are closely entwined, as social disadvantage often yields poor diet quality, and may interact to fuel differential health outcomes. This paper reviews effects of psychosocial stress and diet composition on health in nonhuman primates and their implications for aging and human health. We examined the effects of social subordination stress and Mediterranean versus Western diet on multiple systems. We report that psychosocial stress and Western diet have independent and additive adverse effects on hypothalamic-pituitary-adrenal and autonomic nervous system reactivity to psychological stressors, brain structure, and ovarian function. Compared to the Mediterranean diet, the Western diet resulted in accelerated aging, nonalcoholic fatty liver disease, insulin resistance, gut microbial changes associated with increased disease risk, neuroinflammation, neuroanatomical perturbations, anxiety, and social isolation. This comprehensive, multisystem investigation lays the foundation for future investigations of the mechanistic underpinnings of psychosocial stress and diet effects on health, and advances the promise of the Mediterranean diet as a therapeutic intervention on psychosocial stress.

Keywords: Aging; Anxiety; Brain structure; Mediterranean and Western diet; Microbiome; Mitochondria; Neuroinflammation; Nonhuman primates; Ovarian function; Psychosocial stress; Social isolation; Transcriptome.

Figure 1.. Social subordination appears stressful in female macaques and results in multisystems perturbations that increase risk of disease.

Subordinate monkeys receive more aggression, less affiliative attention (e.g., being groomed), spend more time alone, and are more vigilant than their dominant counterparts (Shively, 1997, 1998; Shively and Day, 2015). Such chronic psychosocial stressors impact multiple systems (inner circle), including: increased inflammation (Walker et al., 2008), impaired glucose metabolism and insulin resistance (Silverstein-Metzler et al., 2022), neurobiological perturbations (Willard et al., 2009), heightened heart rate responses to acute stressors (Shively, 1998), higher morning circulating cortisol concentrations (Shively, 1997), greater cortisol responses to adrenocorticotropin (ACTH) challenge (Kaplan et al., 1986; Shively, 1997), and insensitivity to glucocorticoid negative feedback in dexamethasone suppression tests of the hypothalamic-pituitary–adrenal axis (Kaplan et al., 2010; Shively, 1997). These body conditions can promote the development of disorders and disease (outer circle). Compared to their dominant counterparts, subordinates have greater visceral obesity (Shively et al., 2009b), impaired ovarian function (Adams et al., 1985; Frye et al., 2023; Kaplan et al., 2010), are more likely to exhibit depression-like phenotypes (Shively, 1997), develop more diet-induced coronary and carotid artery atherosclerosis (Shively et al., 2009a; Shively et al., 2009b; Shively et al., 2004), have increased biomarkers of breast and endometrial cancer risk (Shively et al., 2004), and exhibit lower bone density (Kaplan et al., 2010). Notably, all of these observations were made in macaques consuming a Western-like diet. Figure created with Biorender.

Figure 2.

Experimental design of the nonhuman primate randomized trial of Western versus Mediterranean diet consumption. HPA=hypothalamic-pituitary-adrenal; ANS=autonomic nervous system; MRI=magnetic resonance imaging

Figure 3.. Theoretical Framework: Diet effects on stress resilience, susceptibility and the aging of the autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis. The Mediterranean and Western diets are described in detail in Table 1.

NHPs that consumed the Mediterranean diet exhibited enhanced stress resilience as indicated by lower sympathetic activity, brisker and more overt heart rate responses to acute stress, more rapid recovery, and lower cortisol responses to acute psychological stress and adrenocorticotropin (ACTH) challenge. Furthermore, age-related increases in sympathetic activity and cortisol responses to stress were delayed by the Mediterranean diet (Shively et al., 2020). Figure created with Biorender.

Figure 4:

Model of multisystem effects of psychosocial stress and diet composition. Variables in red boxes were measured in nonhuman primates in our randomized preclinical trial. Others were observed in in vitro or rodent studies. SNS: sympathetic nervous system; PNS: parasympathetic nervous system; HRV: heart rate variability; HPA: Hypothalamic-pituitary-adrenal axis