Daniel Baylis

Understanding how we age: insights into inflammaging

Inflammaging is characterized by the upregulation of the inflammatory response that occurs with advancing age; its roots are strongly embedded in evolutionary theory.Inflammaging is believed to be a consequence of a remodelling of the innate and acquired immune system, resulting in chronic inflammatory cytokine production.Complex interrelated genetic, environmental and age-related factors determine an individual’s vulnerability or resilience to inflammaging. These factors include polymorphisms to the promoter regions of cytokines, cytokine receptors and antagonists, age-related decreases in autophagy and increased adiposity. Anti-inflammaging describes the upregulation of the hypothalamic-pituitary axis in response to inflammaging, leading to higher levels of cortisol, which in turn may be detrimental, contributing to less successful ageing and frailty. This may be countered by the adrenal steroid dehydroepiandrosterone, which itself declines with age, leaving certain individuals more vulnerable. Inflammaging and anti-inflammaging have both been linked with a number of age-related outcomes, including chronic morbidity, functional decline and mortality. This important area of research offers unique insights into the ageing process and the potential for screening and targeted interventions.

The age-related increase in low-grade systemic inflammation (Inflammaging) is not driven by cytomegalovirus infection

Aging is accompanied by the development of low‐grade systemic inflammation, termed ‘inflammaging’, characterized by raised serum C‐reactive protein (CRP) and pro‐inflammatory cytokines. Importantly, inflammaging is implicated in the pathogenesis of several of the major age‐related diseases including cardiovascular disease, type 2 diabetes, and dementia and is associated with increased mortality. The incidence of infection with the persistent herpes virus cytomegalovirus (CMV) also increases with age. Cross‐sectional studies have proposed CMV infection as a significant driver of inflammaging, but a definitive case for CMV as a causative agent in inflammaging has not yet been made. We studied longitudinally 249 subjects (153 men, 96 women) who participated in the Hertfordshire Ageing Study at baseline (1993/5, mean age 67·5 years) and at 10 year follow‐up. At both times, anthropometric measurements were made and subjects provided blood samples for analysis of inflammatory status and CMV seropositivity. In the cohort as a whole, serum CRP (P < 0·02) and pro‐inflammatory cytokines TNFα (P < 0·001) and IL‐6 (P < 0·001) were increased between baseline and follow‐up sampling whereas levels of the anti‐inflammatory cytokine IL‐10 were decreased (P < 0·001). These changes to cytokine status over time occurred equally in the 60% of subjects who were seropositive for CMV at baseline and follow‐up, the 8% who were CMV negative at baseline but who became CMV positive by the 10 year follow‐up, and also in the 32% who were CMV seronegative throughout. We conclude that CMV infection is not a primary causative factor in the age‐related increase in systemic inflammation.

Markers of inflammatory status are associated with hearing threshold in older people: findings from the Hertfordshire Ageing Study.

BACKGROUND Age-related hearing loss is a common disabling condition but its causes are not well understood and the role of inflammation as an influencing factor has received little consideration in the literature. OBJECTIVE To investigate the association between inflammatory markers and hearing in community-dwelling older men and women. DESIGN Cross-sectional analysis within a cohort study. SETTING The Hertfordshire Ageing Study. PARTICIPANTS A total of 343 men and 268 women aged 63-74 years on whom data on audiometric testing, inflammatory markers and covariates were available at follow-up in 1995. MAIN OUTCOME MEASURES Average hearing threshold level (across 500-4,000 Hz) of the worst hearing ear and audiometric slope in dB/octave from 500 to 4,000 Hz. RESULTS Older age, smoking, history of noise exposure and male gender (all P < 0.001) were associated with higher mean hearing threshold in the worse ear in univariate analysis. After adjustment for these factors in multiple regression models, four measures of immune or inflammatory status were significantly associated with hearing threshold, namely white blood cell count (r = 0.13, P = 0.001), neutrophil count (r = 0.13, P = 0.002), IL-6 (r = 0.10, P = 0.05) and C-reactive protein (r = 0.11, P = 0.01). None of the inflammatory markers was associated with maximum audiometric slope in adjusted analyses. CONCLUSIONS Markers of inflammatory status were significantly associated with degree of hearing loss in older people. The findings are consistent with the possibility that inflammatory changes occurring with ageing may be involved in age-related hearing loss. Longitudinal data would enable this hypothesis to be explored further.