Sex, the aging immune system, and chronic disease

Bupp, Melanie R. Gubbels

doi:10.1016/j.cellimm.2015.02.002

Cited by 262 publications

(167 citation statements)

References 127 publications

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“…Estrogens are thought to have an anti-inflammatory effect (Gubbels Bupp, 2015; Straub, 2007), inhibiting IL-6 production and gene expression (Liu et al, 2005). Estrogen levels differ both by sex and by menopausal status (Gubbels Bupp, 2015), suggesting that higher levels of estrogens in pre-menopausal females provide greater inhibition of inflammation. In the present study, participants provided self-reports of menopausal status, but only one female reported being menopausal.…”

Section: 0 Discussionmentioning

confidence: 99%

Sex differences in the association between stressor-evoked interleukin-6 reactivity and C-reactive protein

Lockwood

Marsland

Cohen

et al. 2016

Brain, Behavior, and Immunity

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Individuals differ consistently in the magnitude of their inflammatory responses to acute stressors, with females often showing larger responses than males. While the clinical significance of these individual differences remains unclear, it may be that greater inflammatory responses relate to increased systemic inflammation and thereby risk for chronic inflammatory disease. Here, we examined whether acute stressor-evoked interleukin (IL)-6 responses associate with resting levels of C-reactive protein (CRP), a marker of systemic inflammation, and whether this association differs by sex. Subjects were 57 healthy midlife adults (30–51 years; 33% female; 68% white). Blood was drawn before and 30-min after two mental stress tasks: a multisource interference task and a Stroop color word task. Hierarchical regressions controlling for age, sex, race, and BMI tested whether stressor-evoked IL-6 responses were associated with resting CRP and whether this association differed by sex. Results indicated that sex and stressor-evoked IL-6 responses interacted to predict CRP (ΔR2 = .08, B = −1.33, β = −.39, p = .02). In males, larger stressor-evoked IL-6 responses associated with higher CRP, whereas in females, stressor-evoked IL-6 responses showed a non-significant negative association with CRP. These findings indicate that inflammatory responses to acute stressors associate with resting levels of CRP; however, this association differs by sex. Previous literature suggests that there are sex differences in stressor-evoked IL-6 responses, but this is the first study to show sex differences in the relationship between acute inflammatory responses and systemic inflammation. The contribution of these sex differences to inflammatory disease risk warrants further investigation.

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Section: 0 Discussionmentioning

confidence: 99%

Sex differences in the association between stressor-evoked interleukin-6 reactivity and C-reactive protein

Lockwood

Marsland

Cohen

et al. 2016

Brain, Behavior, and Immunity

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“…The two physiological systems most often invoked are the endocrine and immune systems. These of course are known to be related to one another in that sex hormones are well-known to affect immune response (Gubbels Bupp, 2015). As was previously noted, lack of mating or sterilization has been repeatedly reported to lengthen life in numerous species, including all species discussed here, suggesting that reproductive hormones may be partially explanatory.…”

Section: Mechanisms Of Sex Differences In Longevitymentioning

confidence: 99%

“…Although there have been numerous studies assessing various aspects of immune responsiveness in adult humans in which females have often proven to have more robust responses (Ferguson et al, 2013; Gubbels Bupp, 2015; Oertelt-Prigione, 2012), there have been few such studies in infants. Yet given the early survival differences between the sexes, if differential immune competence could be affecting survival differences, then studies of infants might seem warranted.…”

Section: Mechanisms Of Sex Differences In Longevitymentioning

confidence: 99%

Sex Differences in Lifespan

2016

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SUMMARY Sex differences in longevity can provide insights into novel mechanisms of aging, yet they have been little studied. Surprisingly, sex-specific longevity patterns are better known in wild animals. Evolutionary hypotheses accounting for longevity patterns in natural populations include differential vulnerability to environmental hazards, differential intensity of sexual selection and distinct patterns of parental care. Mechanistic hypotheses focus on asymmetric inheritance of sex chromosomes and mitochondria. Virtually all intensively studied species show conditional sex differences in longevity. Humans are the only species in which one sex is known to have a ubiquitous survival advantage. Paradoxically, although women live longer, they suffer greater morbidity particularly late in life. This mortality-morbidity paradox may be a consequence of greater connective tissue responsiveness to sex hormones in women. Human females’ longevity advantage may result from hormonal influences on inflammatory and immunological responses, or greater resistance to oxidative damage; current support for these mechanisms is weak.

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“…Some identified exogenous triggers include smoking (Behnia et al, 2016), air pollution (Fougere et al, 2015), persistent infections (Derhovanessian et al, 2011; Oppermann et al, 2012) and overweight or obesity (Giugliano et al, 2006). Several endogenous factors also play a relevant role, including: overproduction of reactive oxygen species (ROS) (Zhang et al, 2016) and advanced glycation end-products (AGEs) (Yamagishi and Matsui, 2016), mitochondrial dysfunction (Lopez-Lluch et al, 2015), renin-angiotensin system (RAS) deregulation (Duprez, 2006), hormonal changes (Epel and Lithgow, 2014; Gubbels Bupp, 2015), visceral adiposity (Palmer and Kirkland, 2016), changes in the gut microbiota (Biagi et al, 2010) and accumulation of cell debris due to a defective autophagy (Franceschi et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in middle-age and older adults: A systematic review and meta-analysis

Custodero

Mankowski

Lee

et al. 2018

Ageing Research Reviews

124

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Growing evidence suggests chronic low-grade inflammation (LGI) as a possible mechanism underlying the aging process. Some biological and pharmaceutical compounds may reduce systemic inflammation and potentially avert functional decline occurring with aging. The aim of the present meta-analysis was to examine the association of pre-selected interventions on two established biomarkers of inflammation, interleukin-6 (IL-6), and C-reactive protein (CRP) in middle-age and older adults with chronic LGI. We reviewed the literature on potential anti-inflammatory compounds, selecting them based on safety, tolerability, acceptability, innovation, affordability, and evidence from randomized controlled trials. Six compounds met all five inclusion criteria for our systematic review and meta-analysis: angiotensin II receptor blockers (ARBs), metformin, omega-3, probiotics, resveratrol and vitamin D. We searched in MEDLINE, PubMed and EMBASE database until January 2017. A total of 49 articles fulfilled the selection criteria. Effect size of each study and pooled effect size for each compound were measured by the standardized mean difference. I2 was computed to measure heterogeneity of effects across studies. The following compounds showed a significant small to large effect in reducing IL-6 levels: probiotics (−0.68 pg/ml), ARBs (−0.37 pg/ml) and omega-3 (−0.19 pg/ml). For CRP, a significant small to medium effect was observed with probiotics (−0.43 mg/L), ARBs (−0.2 mg/L), omega-3 (−0.17 mg/L) and metformin (−0.16 mg/L). Resveratrol and vitamin D were not associated with any significant reductions in either biomarker. These results suggest that nutritional and pharmaceutical compounds can significantly reduce established biomarkers of systemic inflammation in middle-age and older adults. The findings should be interpreted with caution, however, due to the evidence of heterogeneity across the studies.

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Sex, the aging immune system, and chronic disease

Cited by 262 publications

References 127 publications

Sex differences in the association between stressor-evoked interleukin-6 reactivity and C-reactive protein

Sex differences in the association between stressor-evoked interleukin-6 reactivity and C-reactive protein

Sex Differences in Lifespan

Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in middle-age and older adults: A systematic review and meta-analysis

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