BackgroundChronic inflammation is involved in the pathogenesis of chronic age-associated, degenerative diseases. Pro-inflammatory host responses that are deleterious later in life may originate from evolutionary selection for genetic variation mediating resistance to infectious diseases under adverse environmental conditions.Methodology/Principal FindingsIn the Upper-East region of Ghana where infection has remained the leading cause of death, we studied the effect on survival of genetic variations at the IL10 gene locus that have been associated with chronic diseases. Here we show that an IL10 haplotype that associated with a pro-inflammatory innate immune response, characterised by low IL-10 (p = 0.028) and high TNF-α levels (p = 1.39×10−3), was enriched among Ghanaian elders (p = 2.46×10−6). Furthermore, in an environment where the source of drinking water (wells/rivers vs. boreholes) influences mortality risks (HR 1.28, 95% CI [1.09–1.50]), we observed that carriers of the pro-inflammatory haplotype have a survival advantage when drinking from wells/rivers but a disadvantage when drinking from boreholes (pinteraction = 0.013). Resequencing the IL10 gene region did not uncover any additional common variants in the pro-inflammatory haplotype to those SNPs that were initially genotyped.Conclusions/SignificanceAltogether, these data lend strong arguments for the selection of pro-inflammatory host responses to overcome fatal infection and promote survival in adverse environments.

BackgroundTo test the inflammatory origin of cardiovascular disease, as opposed to its origin in western lifestyle. Population-based assessment of the prevalences of cardiovascular risk factors and cardiovascular disease in an inflammation-prone African population, including electrocardiography and ankle-arm index measurement. Comparison with known prevalences in American and European societies.Methodology/Principal FindingsTraditional population in rural Ghana, characterised by adverse environmental conditions and a high infectious load. Population-based sample of 924 individuals aged 50 years and older. Median values for cardiovascular risk factors, including waist circumference, BMI, blood pressure, and markers of glucose and lipid metabolism and inflammation. Prevalence of myocardial infarction detected by electrocardiography and prevalence of peripheral arterial disease detected by ankle-arm index. When compared to western societies, we found the Ghanaians to have more proinflammatory profiles and less cardiovascular risk factors, including obesity, dysglycaemia, dyslipidaemia, and hypertension. Prevalences of cardiovascular disease were also lower. Definite myocardial infarction was present in 1.2% (95%CI: 0.6 to 2.4%). Peripheral arterial disease was present in 2.8% (95%CI: 1.9 to 4.1%).Conclusions/SignificanceTaken together, our data indicate that for the pathogenesis of cardiovascular disease inflammatory processes alone do not suffice and additional factors, probably lifestyle-related, are mandatory.

A central paradigm in life‐history theory is the trade‐off between offspring number and quality. Several studies have investigated this trade‐off in humans, but data are inconclusive, perhaps because prosperous socio‐cultural factors mask the trade‐off. Therefore, we studied 2461 offspring groups in an area under adverse conditions in northern Ghana with high fertility and mortality rates. In a linear mixed model controlling for differences in age and tribe of the mother and socioeconomic status, each additional child in the offspring group resulted in a 2.3% (95% CI 1.9–2.6%, P < 0.001) lower proportional survival of the offspring. Furthermore, we made use of the polygamous population structure and compared offspring of co‐wives in 388 households, thus controlling for variation in resources between compounds. Here, offspring survival decreased 2.8% (95% CI 2.3–4.0%, P < 0.001) for each increase in offspring number. We interpret these data as an apparent quality–quantity trade‐off in human offspring.

BackgroundThe apolipoprotein-ε4 allele (APOE-ε4) is strongly associated with detrimental outcomes in affluent populations including atherosclerotic disease, Alzheimer’s disease, and reduced lifespan. Despite these detrimental outcomes, population frequencies of APOE-ε4 are high. We hypothesize that the high frequency of APOE-ε4 was maintained because of beneficial effects during evolution when infectious pathogens were more prevalent and a major cause of mortality. We examined a rural Ghanaian population with a high pathogen exposure for selective advantages of APOE-ε4, to survival and or fertility.Methods and findingsThis rural Ghanaian population (n = 4311) has high levels of mortality from widespread infectious diseases which are the main cause of death. We examined whether APOE-ε4 was associated with survival (total follow-up time was 30,262 years) and fertility after stratifying by exposure to high or low pathogen levels. Households drawing water from open wells and rivers were classified as exposed to high pathogen levels while low pathogen exposure was classified as those drawing water from borehole wells. We found a non-significant, but positive survival benefit, i.e. the hazard ratio per APOE-ε4 allele was 0.80 (95% confidence interval: 0.69 to 1.05), adjusted for sex, tribe, and socioeconomic status. Among women aged 40 years and older (n = 842), APOE-ε4 was not associated with the lifetime number of children. However, APOE-ε4 was associated with higher fertility in women exposed to high pathogen levels. Compared with women not carrying an APOE-ε4 allele, those carrying one APOE-ε4 allele had on average one more child and those carrying two APOE-ε4 alleles had 3.5 more children (p = 0.018).ConclusionsContrary to affluent modern-day populations, APOE-ε4 did not carry a survival disadvantage in this rural Ghanaian population. Moreover, APOE-ε4 promotes fertility in highly infectious environments. Our findings suggest that APOE-ε4 may be considered as evolutionarily adaptive. Its adverse associations in affluent modern populations with later onset diseases of aging further characterize APOE-ε4 as an example of antagonistic pleiotropy.

Objective To assess the mortality risk in subsequent years (adjusted for year of birth, nationality, and sex) of former Olympic athletes from disciplines with different levels of exercise intensity.Design Retrospective cohort study. Setting Former Olympic athletes.Participants 9889 athletes (with a known age at death) who participated in the Olympic Games between 1896 and 1936, representing 43 types of disciplines with different levels of cardiovascular, static, and dynamic intensity exercise; high or low risk of bodily collision; and different levels of physical contact. Main outcome measure All cause mortality.Results Hazard ratios for mortality among athletes from disciplines with moderate cardiovascular intensity (1.01, 95% confidence interval 0.96 to 1.07) or high cardiovascular intensity (0.98, 0.92 to 1.04) were similar to those in athletes from disciplines with low cardiovascular intensity. The underlying static and dynamic components in exercise intensity showed similar non-significant results. Increased mortality was seen among athletes from disciplines with a high risk of bodily collision (hazard ratio 1.11, 1.06 to 1.15) and with high levels of physical contact (1.16, 1.11 to 1.22). In a multivariate analysis, the effect of high cardiovascular intensity remained similar (hazard ratio 1.05, 0.89 to 1.25); the increased mortality associated with high physical contact persisted (hazard ratio 1.13, 1.06 to 1.21), but that for bodily collision became non-significant (1.03, 0.98 to 1.09) as a consequence of its close relation with physical contact.Conclusions Among former Olympic athletes, engagement in disciplines with high intensity exercise did not bring a survival benefit compared with disciplines with low intensity exercise. Those who engaged in disciplines with high levels of physical contact had higher mortality than other Olympians later in life.

Background: muscle strength measured as handgrip strength declines with increasing age and predicts mortality. While handgrip strength is determined by lifestyle through nutrition and physical activity, it has almost exclusively been studied in western populations with a sedentary lifestyle. This study aims to investigate the relation between handgrip strength, ageing and mortality in a population characterised by a predominance of malnutrition and manual labour.Design: a population-based longitudinal study.Setting: a traditional African rural population in Ghana.Subjects: nine hundred and twenty-three community-dwelling individuals aged 50 and older.Methods: demographic characteristics were registered. At baseline, height, body mass index (BMI) and handgrip strength were measured and compared with those in a western reference population. Survival of the participants was documented during a period of up to 2 years.Results: handgrip strength was dependent on age, sex, height and BMI. Compared with the western reference population, handgrip strength was lower due to a lower height and BMI but declined over age similarly. Risk of mortality was lower in participants having higher handgrip strength, with a hazard ratio of 0.94 per kg increase (P = 0.002). After adjustment for age, sex, tribe, socio-economic status, drinking water source, height and BMI, only handgrip strength remained predictive of mortality.Conclusion: in a traditional rural African population characterised by malnutrition and manual labour, handgrip strength declines over age and independently predicts mortality similar to western populations. Handgrip strength can be used as a universal marker of ageing.

Socio-economic status is an important determinant of health and survival in rural Africa and necessitates a practical and valid instrument to implement in health studies. Our objective was to investigate the validity of the rapid appraisal method to assess socio-economic status and its ability to identify individuals at risk. Among 1573 households in rural northern Ghana, we calculated the Demographic Health Survey (DHS) wealth index and conducted two rapid appraisal methods: self-reported wealth and interviewer-reported wealth. In addition we followed the 25,184 participants from these households for survival with a mean follow-up of 3.9 years, during which 885 participants died. The DHS wealth index was moderately correlated to self-reported wealth (Spearman's rho 0.59, P<0.001) and interviewer-reported wealth (Spearman's rho 0.75, P<0.001). Mortality risks were significantly higher for people with lower than average self-reported wealth [hazard ratio (HR) 1.30 (95% CI 1.11-1.51)] and lower interviewer-reported wealth [HR 1.40 (95% CI 1.21-1.62)]. Mortality risks were lower for people with higher self-reported wealth [HR 0.81 (95% CI 0.32-2.03)] and higher interviewer-reported wealth [HR 0.84 (95% CI 0.58-1.21)]. Similar discriminative mortality risks were assessed when using tertiles of the DHS wealth index (Ptrend<0.001).

Subclinical hypothyroidism (SCH), defined as elevated thyroid stimulating hormone (TSH) and normal thyroid hormone levels, and cognitive impairment are both common in older people. While the relation between overt hypothyroidism and cognitive impairment is well established, data on the association between SCH and cognitive impairment are conflicting. This systematic review and meta-analysis was performed to assess available evidence on the association of SCH with cognition in community dwelling, relatively healthy older adults. PubMed, EMBASE, Web of Science, COCHRANE, CINAHL, PsycINFO, and Academic Search Premier (January 1966 to April 1, 2015) were searched without language restrictions, as were references of key articles, for studies on the association between SCH and cognition in older adults (>60 years). These studies were reviewed by two independent reviewers according to predefined criteria for eligibility and methodological quality, and data were extracted using standardized forms. Of the 844 reports initially identified, 270 remained after exclusion of duplicates. Of the 270, 15 studies comprising 19,944 subjects, of whom 1,199 had subclinical hypothyroidism were included. Data from the 15 studies was pooled, and meta-analyzed cross-sectionally for global cognition [assessed by Mini-Mental State Examination (MMSE)], executive function, and memory, using random effects models. Pooled effect size (ES) for MMSE was −0.01 (95% CI −0.09, 0.08), with heterogeneity (I2) of 55.1%. Pooled ES was < 0.001 (95% CI −0.10, 0.09) for executive function (I2 = 13.5%), and 0.01 (95% CI −0.12, 0.14) for memory (I2 = 46.9%). In addition, prospective analysis including four studies showed pooled ES of 0.033 (95% CI −0.001 − 0.067) for MMSE (I2 < 0.001%), indicating that subclinical hypothyroidism was not significantly associated with accelerated cognitive decline. This systematic review and meta-analysis provides no evidence that supports an association between SCH and cognitive impairment in relatively healthy older adults.