Sex differences in epigenetic age in Mediterranean high longevity regions.

Sex differences in aging manifest in disparities in disease prevalence, physical health, and lifespan, where women tend to have greater longevity relative to men. However, in the Mediterranean Blue Zones of Sardinia (Italy) and Ikaria (Greece) are regions of centenarian abundance, male-female centenarian ratios are approximately one, diverging from the typical trend and making these useful regions in which to study sex differences of the oldest old. Additionally, these regions can be investigated as examples of healthy aging relative to other populations. DNA methylation (DNAm)-based predictors have been developed to assess various health biomarkers, including biological age, Pace of Aging, serum interleukin-6 (IL-6), and telomere length. Epigenetic clocks are biological age predictors whose deviation from chronological age has been indicative of relative health differences between individuals, making these useful tools for interrogating these differences in aging. We assessed sex differences between the Horvath, Hannum, GrimAge, PhenoAge, Skin and Blood, and Pace of Aging predictors from individuals in two Mediterranean Blue Zones and found that men displayed positive epigenetic age acceleration (EAA) compared to women according to all clocks, with significantly greater rates according to GrimAge (ß = 3.55; p = 1.22 × 10-12), Horvath (ß = 1.07; p = 0.00378) and the Pace of Aging (ß = 0.0344; p = 1.77 × 10-08). Other DNAm-based biomarkers findings indicated that men had lower DNAm-predicted serum IL-6 scores (ß = -0.00301, p = 2.84 × 10-12), while women displayed higher DNAm-predicted proportions of regulatory T cells than men from the Blue Zone (p = 0.0150, 95% Confidence Interval [0.00131, 0.0117], Cohen's d = 0.517). All clocks showed better correlations with chronological age in women from the Blue Zones than men, but all clocks showed large mean absolute errors (MAE >30 years) in both sexes, except for PhenoAge (MAE <5 years). Thus, despite their equal survival to older ages in these Mediterranean Blue Zones, men in these regions remain biologically older by most measured DNAm-derived metrics than women, with the exception of the IL-6 score and proportion of regulatory T cells.

Dairy products consumption is associated with decreased levels of inflammatory markers related to cardiovascular disease in apparently healthy adults: the ATTICA study.

OBJECTIVE: The aim of this work was to investigate the association between consumption of dairy products and levels of various inflammatory markers among adults with no evidence of cardiovascular or other chronic disease. METHODS: The ATTICA study is a cross-sectional survey that enrolled 1514 men (18-87 years old) and 1528 women (18-89 years old) from the Attica region in Greece. Fasting blood samples were collected and dietary habits (including consumption of dairy products [i.e., milk, cheese, and yogurt]) were evaluated using a validated food frequency questionnaire. RESULTS: We observed that C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels of individuals consuming between 11 and 14 servings of dairy products per week were almost 16%, 5%, and 12% lower, respectively, than in those consuming fewer than 8 servings (p < 0.05), while those consuming more than 14 servings per week had 29%, 9%, and 20% lower levels of CRP, IL-6, and TNF-α, respectively (p < 0.01), even after adjustments were made for age, gender, smoking, physical activity, body mass, dietary habits, and other potential confounders. CONCLUSION: We identified an inverse association between dairy products consumption and levels of various inflammatory markers among healthy adults. Additional clinical trials are needed to refute or confirm our findings.

The association between educational status and risk factors related to cardiovascular disease in healthy individuals: The ATTICA study.

PURPOSE: The object of this work was to study the associations between education status and several cardiovascular risk factors in 2271 randomly selected male and female adults. METHODS: The formal education level was used as proxy for socio-economic status; the distribution of the risk factors and the prevalence of risk conditions were analyzed by the different levels of education-"low", "medium", and "high." The association between education level and the investigated measurements was tested by the application of multiple regression analysis. RESULTS: Two hundred and twenty (19.8%) males and 292 (25.3%) females were classified as "low", 471 (42.4%) males and 476 (41.3%) females as "medium", and 421 (37.8%) males and 386 (33.4%) females as "high" educated. Compared with those with "low" education, individuals who reported "high" education had 8% lower systolic (p < 0.001) and 4% lower diastolic (p < 0.001) blood pressure levels, 6% lower blood glucose levels (p < 0.001), 7% lower serum total cholesterol (p < 0.001), 6% higher HDL-cholesterol (p < 0.001), 22% lower lipoprotein-a levels (p < 0.001), 11% lower apoliprotein-B levels (p < 0.001), 15% lower triglycerides (p < 0.001), 45% lower hs-CRP (p < 0.001), 8% lower fibrinogen levels (p < 0.01), and 7% lower white blood cell count (p < 0.001). The associations regarding inflammation markers remained statistically significant even after adjustment for several potential confounders. CONCLUSIONS: Our findings suggest that in primary prevention it is important to focus our attention, especially, on people with low education, since they seem to be rather unprotected against the prevalence of several cardiovascular risk factors.

Socio-economic status in relation to risk factors associated with cardiovascular disease, in healthy individuals from the ATTICA study.

BACKGROUND: Social status has been related with the prevalence and incidence of cardiovascular disease. The aim of this study is to investigate the relationships between socio-economic status (SES) and clinical and biochemical factors related to coronary heart disease, in a sample of cardiovascular disease-free men and women. DESIGN: Cross-sectional survey. METHODS: During 2001-2002, 1514 men (20-87 years old) and 1528 women (20-89 years old) from the Attica region (Greece) were randomly enrolled into the study. Trends in established and emerging cardiovascular risk factors were examined across the participants' socio-economic status. A special index was developed (years of school by annual income) and three socio-economic classes were created. RESULTS: An inverse relationship was found regarding all lipids and glucose levels across the tertiles of the SES index. An inverse association was observed between body mass index, waist-to-hip ratio and SES in men, but not in women. Furthermore, compared to the lowest tertile, individuals who were classified in the highest SES tertile had lower levels of C-reactive protein, fibrinogen, homocysteine, tumour necrosis factor-alpha, interleukin-6 levels and white blood cell counts, even after adjusting for various potential confounders. Finally, a considerable proportion of men and women reported lack of health knowledge and education. CONCLUSIONS: An inverse association between SES and factors related to cardiovascular risk exists, but the causal pathway itself requires more detailed explanation before the social status can have explanatory power.

Education and acute coronary syndromes: results from the CARDIO2000 epidemiological study.

OBJECTIVE: As a measure of socioeconomic status, low educational level is positively associated with the risk of developing adverse health events. The aim of this study was to investigate the relationship between the level of education and the risk of developing non- fatal acute coronary syndromes. METHODS: During 2000 and 2001, 1619 randomly selected subjects from several regions of Greece were entered into a case-control study. Of these, 750 were patients with their first acute coronary heart syndrome event, and 869 were hospitalized controls with no cardiovascular disease in their medical history. Trends in cardiovascular risk factors were then examined across patient and control educational level by years of schooling. FINDINGS: In both patients and controls, education status was related to economic and occupation status, smoking habits, physical inactivity, alcohol consumption and non-compliance to treatment. After adjusting for these and other conventional risk factors, as well as for the effects of age and sex, we found that coronary risk increases by 82% (odds ratio (OR) = 1.82, P <0.05) for individuals with a lower level of education, and by 65% (OR = 1.65, P <0.05) for individuals with an average education, compared to those with an academic education. CONCLUSIONS: Although the least-educated subjects adopted a more adverse lifestyle than the more-educated subjects, the inverse association between education and coronary risk was independent from such factors. The inverse association may be due to psychosocial differences, and prospective cohort studies are needed to confirm or refute these results.