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Chronic Inflammation and Differences in Frailty Between the Sexes


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Posted Today, 05:55 PM


We are all well aware of the differences in life expectancy between women and men. The underlying reasons for the female advantage in longevity are much debated, but since similar sex differences exist across many species, it is likely to have deep roots in evolutionary biology and the complex interactions between reproductive fitness, mating strategies, and biochemistry. More prosaic explanations invoking the consequences of cultural and lifestyle choices that differ characteristically between sexes seem unlikely to be correct.

The situation is more complex than just a matter of life span, however. While living longer, women in late life exhibit a greater burden of disease and dysfunction than equivalently aged men. This seems a paradox, as reliability theory suggests that failing complex machine will have a shorter life span. Yet the data is the data. The research community spends a fair amount of time and effort attempting to find an explanation for sex based disparities in late life health that can explain all of the observed outcomes. Today's open access paper is an example of the process of gathering yet more data that might help researchers to better understand what is going on under the hood.

Inflammaging and the sex-frailty paradox

During aging, the immune cell functionality gradually decreases, resulting in a phenomenon known as "immunosenescence", which undermines both the innate and adaptive immune systems, leading to an increased incidence of disease and infection. Immunosenescence is the basis of inflammaging, a phenomenon that occurs during aging and consists of a chronic and persistent state of low-grade inflammation characterized mainly by the production of components of the innate immune response. The theory posits that excessive stimulation of pro-inflammatory pathways and an ineffective anti-inflammatory response are a driving force behind the development of frailty and age-related diseases.

Specifically, frailty reflects a state of increased vulnerability to stressors, a consequence of the gradual decline in the individual's homeostasis and functional reserves. A sex-associated divergence in frailty and mortality, termed the "sex-frailty paradox", is widely known. This consists of the observation that women, while generally living longer than men, often show higher rates of frailty reflecting a worse health status. This could be due to the fact that men tend to suffer from more malignant conditions (e.g. stroke and ischaemic heart disease), while women mainly from "life-threatening" chronic conditions associated with greater morbidity (e.g. fractures, constipation, depression, and headaches).

Research on sex-specific differences in frailty and its contributing factors suggests that these disparities are probably the result of the complex interplay between biological, psychosocial, and behavioural factors which differ between women and men. Interestingly, some studies have shown a different association between certain inflammatory markers and frailty in women and men. We studied 452 subjects (315 women and 137 men) stratifying them by age (≤ 80, 81-99 and ≥ 100 years) and sex. A 47-item frailty index was calculated. Plasma concentrations of inflammatory markers were analysed by next-generation ELISA.

Women aged ≤ 80 years were less frail while those aged ≥ 100 years were more frail than their male counterparts. Interestingly, the 81-99-year-old group showed similar frailty degree between females and males. The observed differences in frailty index values between women and men in the three age groups paralleled the peculiar associations of biomarker concentrations. This finding was in agreement with the concentrations of IL-10 and TNF-α, which were higher in men aged ≤ 80 years, and with the concentrations of IL-6 and soluble TREM1, which were higher in men aged ≤ 80 as well as in men aged 81-99 years than in women peers. This data may support the fact that immune-senescence is accelerated in men compared to women, resulting in a greater decrease in B lymphocytes and naïve T lymphocytes and a greater increase of memory T lymphocytes and natural killer cells. This alteration of immune cell function results in elevated levels of pro-inflammatory as well as anti-inflammatory cytokines, the so-called inflammaging, and in immune system dysfunction, which may underlie reduced longevity in men.


View the full article at FightAging




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