Przemyslaw Slusarczyk

miR-34a and miR-9 are overexpressed and SIRT genes are downregulated in peripheral blood mononuclear cells of aging humans:

Increased expression of sirtuins lowers the risk of age-related diseases, while their role in the regulation of longevity is not firmly established. Since aging is associated with immunosenescence, we tested whether sirtuin expression was modified in peripheral blood mononuclear cells (PBMC) in an age-related manner and whether this might result from altered expression of the selected miRNAs. The expression of seven SIRT genes and of SIRT1 mRNA-interacting miR-9, miR-34a, miR-132, and miR-199a-5p was evaluated by real-time PCR in PBMC originating from young (Y, n = 57, mean age 27 ± 4.3 years), elderly (E, n = 52, 65 ± 3.4 years), and long-lived (L, n = 56, 94 ± 3.5 years) individuals. Older age was associated with a decreased expression of the majority of the SIRT genes. Most severely affected were median expressions of SIRT1 (P = 0.000001 for the whole studied group, Y vs. E: P < 0.000001, Y vs. L: P < 0.000001), and of SIRT3 (P = 0.000001, Y vs. E: P = 0.000004, Y vs. L: P = 0.000028). Older age was also associated with the increased median expression of miR-34a (P = 0.000001, Y vs. E: P = 0.001, Y vs. L: P = 0.000004) and of miR-9 (P = 0.05, Y vs. L: P = 0.054). In functional studies, miR-9 interacted with the 3′UTR of SIRT1 mRNA. The SIRT1 mRNA level negatively correlated with the expression of miR-34a (r = −0.234, P = 0.003). In conclusion, age-related decrease of SIRT1 expression in PBMC might in part result from overexpression of miR-34a and miR-9. In addition, the sustained expression of the SIRT genes in PBMC is not a prerequisite to longevity in humans but might be one of the reasons for the immune system dysfunction in the elderly. Impact statement High expression of sirtuins, particularly SIRT1, lowers the risk of age-related diseases and probably slows down the rate of aging; therefore, their sustained expression should be one of the features of longevity. However, in this work we show that in peripheral blood mononuclear cells (PBMC) of long-lived individuals, expression of majority of the SIRT genes is significantly lower than in cells of young study subjects. In long-lived individuals, downregulation of SIRT1 coexists with upregulation of SIRT1 mRNA-interacting miR-34a and miR-9, indicating the role of epigenetic drift in age-dependent deregulation of SIRT1 expression. Such constellation of SIRT1, miR-34a, and miR-9 expression in PBMC of successfully aging long-lived individuals indicates that, at least in these individuals, it is not a risk factor for morbidity and mortality. It might however affect the function of the immune system and, therefore, aging individuals can profit from interventions increasing the level of SIRT1.

Age-related changes of leptin and leptin receptor variants in healthy elderly and long-lived adults

Aging is usually associated with hyperleptinemia and leptin resistance, both increasing the risk of age‐related diseases. It was relevant to establish if healthily aging, non‐obese individuals develop changes in leptin, the soluble leptin receptor (OB‐Re), free leptin index (FLI), in methylation of the leptin receptor gene (LEPR) promoter, and in the expression of long (OB‐Rb) and short (OB‐Ra) leptin receptor isoforms.

Prevalence of chronic pain in the elderly Polish population – results of the PolSenior study

Introduction Pain is the most common complaint of elderly people. In Poland, no large studies on the prevalence of chronic pain in the elderly were conducted until recently. Material and methods The study was a part of the PolSenior project, a cross-sectional multidisciplinary study on ageing of the Polish population, and included a randomly selected group of 716 people aged 55–59 years, and 4979 people over 65 years. The survey was conducted through a standardized questionnaire. An evaluation of pain occurrence, location, intensity and coexistence of pains in relation to gender, age and use of health care was performed. Results Chronic pain affected 42.0% of respondents aged 65 years and over (48.6% of women and 35.8% of men) as compared to 35.2% of the pre-elderly. The most common pain locations were the lumbar region (51.6%) and knees (41.0%). The average number of pain sites was 3.1 ±2.3. Average intensity of pain was 6.2 points on the VAS scale in people over 65 years and 6.0 points in the pre-elderly (NS). Average pain intensity increased significantly from 5.7 points in patients reporting pain in one place to 7.2 points in those reporting six pain sites. Elderly respondents with pain compared to those without pain more frequently reported physician visits performed at least once a month (54.6% vs. 48.4%, p < 0.001). Conclusions Polish elderly most frequently complained of low back and lower limb pain. In respondents reporting many sites of pain, an increase in the intensity of pain was observed. Elderly patients with chronic pain often use medical care.

Self-rated health and its association with all-cause mortality of older adults in Poland: The PolSenior project

OBJECTIVES Predictive effect of self-rated health (SRH) on mortality in older adults has been observed. The purpose of the study was to analyze this association in Poles aged 65+. METHODS Data were obtained from the nationwide, multidisciplinary PolSenior project, conducted in a representative sample of older population. The study group comprised 4049 respondents (48.0% women) without significant cognitive deficit. SRH was measured using Visual Analog Scale. The analysis included selected socio-economic, health status and life-style factors. Mortality data were retrieved from the state registry. RESULTS During 5-year period, 414 women (21.4%) and 672 men (31.8%) have died, including 17.5% of women and 26.6% of men with good, 21.6% and 32.9% with fair, 36.2% and 55.3% with poor SRH, respectively. Kaplan-Meier survival curves for SRH revealed significant differences for both genders. Univariate Cox regression analysis revealed significant hazard ratios (HRs) for mortality among women and men with poor compared to good SRH [2.48 (1.83-3.37); 2.62 (2.04-3.36), respectively] and those with fair compared to good SRH [1.29 (1.03-1.60); 1.29 (1.10-1.52), respectively]. Age-adjusted HRs for mortality were significant between groups with poor and good SRH [women: 1.98 (1.46-2.68), men: 2.06 (1.60-2.64)]. Multivariate Cox proportional hazard regression model including revealed significant HRs for mortality between women with poor and good SRH [1.67 (1.06-2.64)]. CONCLUSIONS SRH was associated with mortality in both genders. After adjustment for age, this relationship was maintained in respondents with poor compared to good SRH. Inclusion of potential confounders demonstrated that SRH was an independent predictor of mortality only in women.