Focus on senescence: Clinical significance and practical applications.

The older population is increasing worldwide, and life expectancy is continuously rising, predominantly thanks to medical and technological progress. Healthspan refers to the number of years an individual can live in good health. From a gerontological viewpoint, the mission is to extend the life spent in good health, promoting well-being and minimizing the impact of aging-related diseases to slow the aging process. Biologically, aging is a malleable process characterized by an intra- and inter-individual heterogeneous and dynamic balance between accumulating damage and repair mechanisms. Cellular senescence is a key component of this process, with senescent cells accumulating in different tissues and organs, leading to aging and age-related disease susceptibility over time. Removing senescent cells from the body or slowing down the burden rate has been proposed as an efficient way to reduce age-dependent deterioration. In animal models, senotherapeutic molecules can extend life expectancy and lifespan by either senolytic or senomorphic activity. Much research shows that dietary and physical activity-driven lifestyle interventions protect against senescence. This narrative review aims to summarize the current knowledge on targeting senescent cells to reduce the risk of age-related disease in animal models and their translational potential for humans. We focused on studies that have examined the potential role of senotherapeutics in slowing the aging process and modifying age-related disease burdens. The review concludes with a general discussion of the mechanisms underlying this unique trajectory and its implications for future research.

Aberrant telomeric structures and serum markers of telomere dysfunction in healthy aging: a preliminary study.

Telomeres undergo a progressive shortening process as individuals age, and it has been proposed that severely shortened and dysfunctional telomeres play a role in the aging process and the onset of age-related diseases in human beings. An emerging body of evidence indicates that the shortening of telomeres in cultured human cells is also influenced by other replication defects occurring within telomeric repeats. These abnormalities can be detected on metaphase chromosomes. Recent studies have also identified a set of serological markers for telomere dysfunction and DNA damage (elongation factor 1α [EF-1α], stathmin, and N-acetyl-glucosaminidase). With this study, the correlation between telomere abnormalities (by FISH) and these biomarkers as measured in blood serum (by ELISA) from a cohort of 22 healthy subjects at different ages (range 26-101 years) was analyzed. A strong positive correlation between aging and the presence of aberrant telomere structures, sister telomere loss (STL), and sister telomere chromatid fusions (STCF) was detected. When serum markers of telomere dysfunction were correlated with telomere abnormalities, we found that stathmin correlated with total aberrant telomeres structures (r = 0.431, p = 0.0453) and STCF (r = 0.533, p = 0.0107). These findings suggest that serum stathmin can be considered an easy-to-get marker of telomere dysfunction and may serve as valuable indicators of aging.

Telomere length and 4-year changes in cognitive function in an older Mediterranean population at high risk of cardiovascular disease.

BACKGROUND: Cognitive decline, a common process of brain ageing, has been associated with telomere length (TL). Delving into the identification of reliable biomarkers of brain ageing is essential to prevent accelerated cognitive impairment. METHODS: We selected 317 non-smoking 'Prevención con Dieta Mediterránea-Plus' (PREDIMED-Plus) participants (mean age, 65.8 ± 5.0 years) with metabolic syndrome from two trial centres who were following a lifestyle intervention. We measured TL and cognitive function at baseline and after 3 and 4 years of follow-up, respectively. Associations between baseline or 3-year changes in TL and baseline or 4-year changes in cognitive function were analysed using multivariable regression models. RESULTS: Baseline TL was not associated with baseline cognitive performance. Nevertheless, longer baseline TL was associated with improved 4-year changes in the Executive Function domain (ß: 0.29; 95%CI: 0.12 to 0.44; P < 0.001) and the Global Cognitive Function domain (ß: 0.19; 95%CI: 0.05 to 0.34; P = 0.010). Besides, a positive association was found between longer baseline TL and improved 4-year changes in the animal version of the Verbal Fluency Test (ß: 0.33; 95%CI: 0.12 to 0.52; P = 0.002). By contrast, 3-year changes in TL were not associated with changes in cognitive function after 4 years. CONCLUSIONS: Longer baseline TL could protect from cognitive decline and be used as a useful biomarker of brain ageing function in an older Mediterranean population at risk of cardiovascular disease and cognitive impairment.

Tai chi, irisin and cognitive performance: a clinical and biological investigation in older adults.

BACKGROUND: Skeletal muscle is the main source of circulating irisin, both at rest and during physical activity. Previous studies have suggested that irisin can improve cognitive abilities. AIMS: We explored whether six months of Tai Chi (TC) practice can modulate such a relationship in healthy older persons. METHODS: This is a prospective clinical study to evaluate the effects of TC practice as compared with low intensity exercise (LI) and no exercise (NE) control groups on plasmatic irisin levels and cognitive performance. Forty-two healthy older persons were stratified into three groups according to physical activities. Biochemical assay and cognitive functions were assessed at the baseline and after six months. RESULTS: A significant change was found in circulating irisin levels in TC as compared with NE group (p = 0.050) across time. At six months in TC group irisin levels significantly correlated with a verbal memory test (p = 0.013) controlled by age and education. CONCLUSION: Our results suggest the potential benefits for cognitive health of TC practice by irisin levels modulation.

Dysglycemia, gender, and cognitive performance in older persons living with mild cognitive impairment: findings from a cross-sectional, population-based study.

OBJECTIVE: This study aims to examine the relationship between dysglycemia - also known as pre-diabetes or impaired glucose tolerance- and cognitive abilities in an older population living Mild Cognitive Impairment (MCI) and stratified by gender. STUDY DESIGN: This is a retrospective study with data gathered from a large Italian clinical-based database. MAIN OUTCOME MEASURES: The evaluation of cognitive performances by the Mini-Mental State Examination and the Addenbrooke's Cognitive Examination Revised rating scale as tests of screening and a comprehensive neuropsychological evaluation of several cognitive areas. RESULTS: The study comprised 682 subjects (445 F/237 M) with a mean age of 76.08 ± 9.03 (range: 66-93) years. In all population, subjects with dysglycemia 193 (28.3%) had significantly poorer performance in memory (p = 0.006) and logic reasoning (p = 0.007) when compared with subjects without dysglycemia. The linear regression analyses revealed significant differences in the correlates of cognitive domains between gender groups. Independent of multiple covariates, women with dysglycemia showed worse performances in attention and short-term memory domains as compared with men. Even in the absence of dysglycemia women were more likely to show lower score in screening test of general cognition and attention. CONCLUSIONS: Our findings suggest that dysglycemia in older individuals with MCI is associated with declines in specific cognitive domains, potentially influenced by gender. Implementing a comprehensive approach involving risk stratification and preventive strategies may be more effective in averting further cognitive decline in this high-risk population.

Medication review and deprescribing in different healthcare settings: a position statement from an Italian scientific consortium.

Recent medical advancements have increased life expectancy, leading to a surge in patients affected by multiple chronic diseases and consequent polypharmacy, especially among older adults. This scenario increases the risk of drug interactions and adverse drug reactions, highlighting the need for medication review and deprescribing to reduce inappropriate medications and optimize therapeutic regimens, with the ultimate goal to improving patients' health and quality of life. This position statement from the Italian Scientific Consortium on medication review and deprescribing aims to describe key elements, strategies, tools, timing, and healthcare professionals to be involved, for the implementation of medication review and deprescribing in different healthcare settings (i.e., primary care, hospital, long-term care facilities, and palliative care). Challenges and potential solutions for the implementation of medication review and deprescribing are also discussed.

Aging, Cancer, and Inflammation: The Telomerase Connection.

Understanding the complex dynamics of telomere biology is important in the strong link between aging and cancer. Telomeres, the protective caps at the end of chromosomes, are central players in this connection. While their gradual shortening due to replication limits tumors expansion by triggering DNA repair mechanisms, it also promotes oncogenic changes within chromosomes, thus sustaining tumorigenesis. The enzyme telomerase, responsible for maintaining telomere length, emerges as a central player in this context. Its expression in cancer cells facilitates the preservation of telomeres, allowing them to circumvent the growth-limiting effects of short telomeres. Interestingly, the influence of telomerase extends beyond telomere maintenance, as evidenced by its involvement in promoting cell growth through alternative pathways. In this context, inflammation accelerates telomere shortening, resulting in telomere dysfunction, while telomere elements also play a role in modulating the inflammatory response. The recognition of this interplay has promoted the development of novel therapeutic approaches centered around telomerase inhibition. This review provides a comprehensive overview of the field, emphasizing recent progress in knowledge and the implications in understanding of cancer biology.

A narrative review on mild behavioural impairment: an exploration into its scientific perspectives.

In clinical practice, the admission of patients with late-onset psychological and behavioural symptoms is frequent, regardless of the presence or absence of cognitive decline. These symptoms commonly occur in the prodromal stage of dementia and can precede the onset of dementia. While the concept of Mild Cognitive Impairment (MCI) -which is defined as a level of cognitive impairment insufficient to impact daily functioning- is well established, the notion of Mild Behavioural Impairment (MBI) is not yet widely recognized. However, studies have demonstrated that the presence of MBI in both cognitively normal patients and individuals with MCI is associated with an increased risk of dementia progression. Thus, MBI may serve as a neurobehavioral indicator of pre-dementia risk states. This narrative review aims to discuss the evolution of the term, the relevant clinical aspects, and potential biomarkers that may contribute to the clinical definition of MBI. The objective is to assist clinicians in recognizing the diagnosis and differentiating it from psychiatric syndromes, as well as identifying possible etiologies of neurodegeneration.

Hypomagnesemia and incident delirium in hospitalized older persons.

BACKGROUND: Altered serum magnesium (Mg) levels in older persons have been hypothesized to have a role in predicting hospitalization and mortality. Hypomagnesemia and delirium are frequent problems in older patients, but no study has evaluated such an association in acute geriatric setting. AIMS: We investigated the impact of hypomagnesemia on the incidence of delirium in an acute geriatric setting. METHODS: This retrospective study was conducted on 209 older hospitalized patients. All subjects underwent a comprehensive geriatric assessment. Mg was measured in serum by routine laboratory methods. The presence of incident delirium was determined by the 4AT screening tool. A logistic regression model was used to assess the association between serum Mg and delirium controlling for multiple covariates. RESULTS: 209 patients (77.9% women) were included in the study. The mean age of the participants was 85.7 ± 6.50 years (range 65-100). 27 subjects (12.9%) developed delirium during the hospitalization, with no difference between genders. Subjects with delirium had lower serum magnesium levels than those without (1.88 ± 0.34 versus 2.04 ± 0.28; p = 0.009). Delirium risk was significantly higher in patients with lower serum magnesium levels (OR 5.80 95% CI 1.450-23.222; p = 0.013), independent of multiple covariates. CONCLUSION: Our data show that low serum Mg level is a good predictor of incident delirium in acute geriatric settings. Present findings have relevant implications for clinical management, highlighting the need for analyzing Mg concentration carefully. Whether Mg supplementation in patients with hypomagnesemia could lead to delirium prevention and/or control needs further investigation.

The correlates of post-surgical haematoma in older adults with proximal femoral fractures.

BACKGROUND: Little is known about the incidence of haematoma, and clinical correlates among orthogeriatric patients. AIMS: This study aims to describe the incidence of haematoma after surgical repair of hip fracture and to identify the clinical correlates of haematoma among orthogeriatric patients. METHODS: Two orthopaedic surgeons and a dedicated operator using ultrasound technique, each other in blindness, evaluated 154 orthogeriatric patients during their hospital stay. All patients received a comprehensive geriatric assessment. We investigated the concordance between clinical diagnosis and ultrasound detection of haematoma, and then we explored the clinical correlates of the onset of post-surgical haematoma. RESULTS: Blood effusion at the surgical site was detected in 77 (50%) patients using ultrasound technique; orthopaedic surgeons reached a clinical agreement about post-surgical haematoma in 18 (23%) patients. The sensitivity of clinical evaluation was 0.66, and the specificity was 0.70. Independent of age, clinical, pharmacological, and surgical confounders, proton pump inhibitors (PPIs) were associated with post-surgical haematoma (OR 2.28; 95% CI 1.15-4.49). A tendency towards association was observed between selective serotonin reuptake inhibitors and post-surgical haematoma (OR 2.10; 95% CI 0.97-4.54), CONCLUSIONS: Half of older patients undergoing surgical repair of proximal femoral fracture develop a post-surgical haematoma. Clinical assessment, even if made by senior orthopaedic surgeons, underestimates the actual occurrence of post-surgical haematoma compared to ultrasound detection. Ultrasound technique may help to detect haematoma larger than 15 mm better than clinical assessment. PPIs's use is a risk factor for post-surgical haematoma independent of several medical and surgical confounders.

Dementia, infections and vaccines: 30 years of controversy.

This paper reports the proceedings of a virtual meeting convened by the European Interdisciplinary Council on Ageing (EICA), to discuss the involvement of infectious disorders in the pathogenesis of dementia and neurological disorders leading to dementia. We recap how our view of the infectious etiology of dementia has changed over the last 30 years in light of emerging evidence, and we present evidence in support of the implication of infection in dementia, notably Alzheimer's disease (AD). The bacteria and viruses thought to be responsible for neuroinflammation and neurological damage are reviewed. We then review the genetic basis for neuroinflammation and dementia, highlighting the genes that are currently the focus of investigation as potential targets for therapy. Next, we describe the antimicrobial hypothesis of dementia, notably the intriguing possibility that amyloid beta may itself possess antimicrobial properties. We further describe the clinical relevance of the gut-brain axis in dementia, the mechanisms by which infection can move from the intestine to the brain, and recent findings regarding dysbiosis patterns in patients with AD. We review the involvement of specific pathogens in neurological disorders, i.e. SARS-CoV-2, human immunodeficiency virus (HIV), herpes simplex virus type 1 (HSV1), and influenza. Finally, we look at the role of vaccination to prevent dementia. In conclusion, there is a large body of evidence supporting the involvement of various infectious pathogens in the pathogenesis of dementia, but large-scale studies with long-term follow-up are needed to elucidate the role that infection may play, especially before subclinical or clinical disease is present.

Dealing with dehydration in hospitalized oldest persons: accuracy of the calculated serum osmolarity.

BACKGROUND:  Assessment of hydration status is complex and difficult to detect in older persons. Different methods have been developed to determine hydration status in clinical settings, but their diagnostic accuracy remains questionable. AIMS: The aim of this study was to determine and compare the diagnostic accuracy of all methods routinely used in acute settings to detect dehydration in a cohort of hospitalized oldest-old persons, using as primary reference standard blood urea nitrogen (BUN) to creatinine ratio. METHODS:  This retrospective study was conducted on 59 oldest-old subjects at hospital admission in an acute setting, with complete physical, biochemical, bioelectrical impedance analysis (BIA) and ultrasound assessment, including inferior vena cava diameters. RESULTS: Fifty-nine (45 women/14 men) subjects, with a mean age of 87.4 ± 5.9 years, were studied. Based on the value of the BUN/creatinine ratio, the whole population was divided into hyperhydrated (n = 10), normohydrated (n = 42), and dehydrated (n = 7) groups. Among parameters indicating the hydration status, serum sodium levels (p < 0.0001), serum chloride levels (p = 0.010), calculated plasma osmolarity (p < 0.0001), and fat mass (FM) (p = 0.030) differed significantly among groups. A ROC analysis showed that the highest and most significant value for dehydration detection was the calculated plasma osmolarity (AUC: 0.820, p = 0.013), which significantly correlated with clinical parameters including heart rate (r = 0.300; p = 0.021), capillary refill (r = 0.379; p = 0.013) and systolic blood pressure (r = - 0.261; p = 0.046). DISCUSSION: The measurement of calculated serum osmolarity is simple and inexpensive and may quickly provide high sensitivity and specificity indication of dehydration in hospitalized oldest-old persons.

Fighting social isolation in times of pandemic COVID-19: the role of video calls for older hospitalized patients.

BACKGROUND: Loneliness and social isolation are associated with anxiety and psychological discomfort, especially amongst the oldest and fragile persons. AIMS: SILVER evaluates the acceptance of video calls by old hospitalized patients and their relatives during the ban on visits due to the COVID-19. Moreover, SILVER evaluates if the use of different communication technology is associated with different outcomes in terms of anxiety, fear of self and of others' death and mood. METHODS: SILVER is an observational multicentre study. Patients hospitalized in two geriatric units in Switzerland and in one orthogeriatric unit in Italy and their relatives were enrolled. Participants can freely choose to use phone or video calls and were evaluated over a week. We measured anxiety, fear of death and mood at baseline and at the end of the study with standard scales. The use of video or phone calls was associated to a change in these parameters by two-way ANOVA for repeated measures. RESULTS: Sixty-four patients and relatives were enrolled, 26.5% used phone calls and 73.5% video calls. The use of video calls was associated with a reduction in anxiety and fear of death in patients and relatives as compared to participants using phone calls. DISCUSSION: Old patients and their relatives accepted and appreciated the use of video calls during hospitalization; moreover, participant using video calls appears to be less anxious and less afraid of death. CONCLUSIONS: Video calls may be a useful communication tool for hospitalized older patients to keep social relationships with relatives and reduce their anxiety and fear of death. TRIAL REGISTRATION: Retrospectively registered on 1st September 2021 in ClinicalTrials.gov (NCT05000099).

Handgrip strength predicts length of hospital stay in an abdominal surgical setting: the role of frailty beyond age.

BACKGROUND: Chronological age per se cannot be considered a prognostic risk factor for outcomes after elective surgery, whereas frailty could be. A simple and easy-to-get marker for frailty, such as handgrip strength (HGS), may support the surgeon in decision for an adequate healthcare plan. AIMS: The aims of this study were to: (1) determine the prevalence of frailty in an abdominal surgery setting independent of age; (2) evaluate the predictive validity of HGS for the length of hospital stay (LOS). METHODS: This is a retrospective study conducted in subjects who underwent abdominal surgical procedures. Only subjects with complete cognitive, functional, nutritional assessments and available measurement of HGS at admission were included. A final cohort of 108 patients were enrolled in the study. RESULTS: Subjects had a mean age of 67.8 ± 15.8 years (age range 19-93 years old) and were mostly men. According to Fried's criteria, 17 (15.7%, 4F/13 M) were fit, 58 (23.7%; 24F/34 M) were pre-frail and 33 (30.6%; 20F/13 M) were frail. As expected, HGS significantly differed between groups having frail lower values as compared with pre-frail and fit persons (fit: 32.99 ± 10.34 kg; pre-frail: 27.49 ± 10.35 kg; frail: 15.96 ± 9.52 kg, p < 0.0001). A final regression analysis showed that HGS was significantly and inversely associated with LOS (p = 0.020) independent of multiple covariates, including age. DISCUSSION: Most of the population undergoing abdominal surgery is pre-frail or frail. The measurement of handgrip strength is simple and inexpensive, and provides prognostic information for surgical outcomes. Muscle strength, as measured by handgrip dynamometry, is a strong predictor of LOS in a surgical setting.

Uric acid and late-onset Alzheimer's disease: results from the ReGAl 2.0 project.

BACKGROUND: It has been suggested that oxidative stress may have a role in the pathogenesis of Alzheimer's disease (AD). Serum uric acid (UA) could exert neuroprotective effects via its antioxidant capacities. Many studies investigated serum UA levels in subjects with AD, but to date, results are conflicting and evidence in old age subjects is weak. AIMS: In this study, we assess whether serum UA levels would be altered in the AD old age subjects compared to those of initial cognitive impairment and healthy controls. METHODS: This is a retrospective study with data gathered from the ReGAl 2.0 project (Rete Geriatrica Alzheimer-Geriatric Network on Alzheimer's disease), a large Italian multicentric clinical-based study. A cohort of 232 subjects, including 65 (healthy controls HC), 95 mild cognitive impairment (MCI), and 72 AD, were included in the study. Serum UA was measured in all subjects by routine laboratory method. RESULTS: The sample population includes 232 subjects, mostly women with a mean age of 79.16 ± 5.64 (range 66-93) years. No significant difference was found in gender distribution between groups. No significant correlation was found in all populations between age and uric acid levels. AD group had significantly lower UA levels as compared with HC. The association of uric acid with AD presence after adjusting for age, gender, body mass index (BMI) and creatinine levels showed that uric acid level was independently associated with the diagnosis of AD. CONCLUSIONS: These data indicate that serum UA is reduced in AD, supporting that UA may have a potential protective role against AD in old age.

Serum alkaline phosphatase is elevated and inversely correlated with cognitive functions in subjective cognitive decline: results from the ReGAl 2.0 project.

BACKGROUND: Alkaline phosphatase has been found on neuronal membranes and plasma alkaline phosphatase (ALP) activity increases during brain injury and cerebrovascular diseases, suggesting that its levels may reflect the neuronal loss. It is known that ALP is higher in subjects affected by Alzheimer's dementia and inversely correlated with cognitive functions. No study has investigated the relationship between ALP and cognitive functions in old-age subject with pre-clinical cognitive impairment. METHODS: This is a cross-sectional study with data gathered from the ReGAl 2.0 project (Rete Geriatrica Alzheimer-Geriatric Network on Alzheimer's disease), a large Italian multicentric clinical-based study. A cohort of 209 old-age subjects healthy controls (HC), Subjective cognitive decline (SCD), and Mild Cognitive Impairment (MCI) was included in the study. Cognitive performances were assessed with a large neuropsychological battery. The same day, serum alkaline phosphatase activity was measured in all subjects. RESULTS: We found that the SCD group had significantly higher ALP levels as compared with HC (p = 0.001). Among all neuropsychological tests, in all population ALP levels negatively correlated with scores at attentional matrices (r = - 0.243, p = 0.002), Digit Span Forward (r = - 0.241, p = 0.003) and Letter Fluency Test (r = - 0.196, p = 0.044). Attentional Matrices (r = - 0.208, p = 0.014) and Letter Fluency Test (r = - 0.229, p = 0.019) remained significantly correlated with ALP even after controlling for gender. In the SCD group, only the Attentional Matrices significantly and negatively correlated with ALP (r = - 0.344 p = 0.035), while no significant correlations were found in HC or MCI. CONCLUSIONS: Results indicate that serum alkaline phosphatase activity is increased in SCD and inversely correlates with cognitive functions. Further studies are needed to investigate the role of ALP in the progression to AD.

Beta-carotene, telomerase activity and Alzheimer's disease in old age subjects.

PURPOSE: Advancing age represents the strongest risk factor for Alzheimer's disease (AD), and the identification of biomarkers able to define what characterizes physiological aging from AD may represent a potential starting point for novel preventive strategies. Among these biomarkers, telomeres seem to be a promising target. Interestingly, high intake of carotenoid-rich food may play a role in protecting telomeres by oxidative stress reduction. Accordingly, low plasma ß-carotene concentrations have been found in AD subjects when compared with cognitively healthy subjects. In this study, we aim at investigating the hypothesis that low ß-carotene might be associated with markers of accelerated cellular aging, including leucocyte telomere length (LTL) and peripheral mononuclear cell (PBMC) telomerase activity in a cohort of old age subjects. METHODS: The study was conducted in 68 old age subjects, 37 AD, and 31 age-matched healthy controls. In all subjects, ß-carotene plasma level, LTL and peripheral telomerase activity were measured. RESULTS: In all populations, ß-carotene significantly and positively (r = 0.320, p = 0.008) correlated with telomerase activity, independent of gender. A model having telomerase activity levels as the dependent variable, and age, gender, smoking habit, and ß-carotene as independent variables, confirmed that ß-carotene was independently associated with telomerase activity (ß = 0.319, p = 0.012). Subjects affected by AD had significantly lower plasmatic levels of ß-carotene (448 ± 66 mg/ml vs 497 ± 59 mg/ml, p = 0.001) and LTL (0.53 ± 0.25 vs 0.69 ± 0.29; p = 0.009) as compared with healthy controls. Β-carotene plasma level was associated with AD diagnosis (OR 0.988; IC95% 0.978-0.997; p = 0.013) independently of age, gender, smoking habit, ApoE genotype, and LTL. CONCLUSION: Our data show that ß-carotene may modulate telomerase activity in old age. Moreover, lower plasma ß-carotene levels, correlating with peripheral telomerase activity, are associated with AD diagnosis independent of multiple covariates.

The Importance of Cellular Senescence in Frailty and Cardiovascular Diseases.

Frailty is a complex clinical syndrome, progressively described in the last thirty years, resulting from multiple impairments across many organs and systems and characterized by a reduction in physiological reserves and increased vulnerability to stressors, as well. Cardiovascular diseases (CVDs) are a common health problem in very old populations. Age-related changes occur throughout the body and in all organs, including the cardiovascular system. Cellular senescence links age-related CVDs and frailty by many mechanisms of particular interest in the aging biology and geriatric syndromes. Cellular senescence may represent the pivotal factor with its senescence-associated secretory phenotype (SASP) leading to systemic inflammation. In this context, SASP may represent the key element in the association between aging, frailty and the development of age-related CVDs.

Probiotics and bone disorders: the role of RANKL/RANK/OPG pathway.

The skeleton is the framework and in charge of body configuration preservation. As a living tissue, bones are constantly being formed and absorbed. Osteoblasts and osteoclasts are the main bone cells and balance between their activities indicates bone health. Several mechanisms influence the bone turnover and RANKL/RANK/OPG pathway is one of them. This system, whose components are part of the tumor necrosis factor (TNF) superfamily, exists in many organs and could play a role in bone modeling and remodeling. RANKL/RANK pathway controls osteoclasts activity and formation. In addition, they are identified as key factors on bone turnover in different pathological situations. At the same time, OPG (RANKL's decoy receptor) plays role as a bone-protective factor by binding to RANKL and prevention of extra resorption. The lack of balance between RANKL and OPG could result in excessive bone resorption. Probiotics, the beneficial microorganisms for human health, entail bones in their advantages. Recent studies suggest that probiotics could reduce inflammatory factors (for example TNF-α and IL-1ß) and increase bone OPG expression. In addition, probiotics have shown to maintain bones in various ways. Although current evidence is not enough for definitive approval of probiotics' efficacy on RANKL/RANK/OPG, its positive responses from conducted studies are significant. Understanding of the probiotics' effects on RANKL/RANK/OPG pathway will help focus future studies, and assist in developing efficient treatment strategies.

Lower serum levels of IL-13 is associated with increased carotid intima-media thickness in old age subjects.

BACKGROUND: Cardiovascular diseases due to atherosclerosis represent the major cause of disability and mortality in old age subjects. The atherosclerotic process is linked to a low grade of systemic inflammation with the involvement of many cytokines and inflammatory proteins. Among them, evidence from animal studies suggests that IL-13 has a protective property. However, the role of IL-13 in the pathogenesis of atherosclerosis in humans is still unknown. AIMS: With this study, we aim to investigate a potential association between IL-13 and carotid intima-media thickness (IMT) in old age subjects. METHODS: This is a retrospective study conducted among 79 old age subjects (over 75 years old). All subjects underwent IMT assessment by high-resolution B-mode ultrasonography and IL-13 measurement in serum by ELISA. RESULTS: Subjects (41 M/38F) had a mean age of 81.0 ± 4.5 years and were mostly overweight. Stratifying the whole cohort by IMT thickness (IMT ≤ 0.9, n = 17; IMT ≥ 1 and ≤ 1.3, n = 50; IMT ≥ 1.4, n = 12) among the main variables explored, only BMI and triglycerides differed among groups, having subjects with higher IMT significantly higher BMI and lower triglycerides. Serum IL-13 levels significantly differed among groups having subjects with IMT ≥ 1.4 lower levels as compared to other groups (p < 0.0001). In all sample population, IMT values significantly correlate with IL-13 levels (r = - 0.454, p < 0.0001). Indeed, a linear regression analysis showed that independent of age, gender, body mass index, triglycerides, systolic blood pressure, statin use and smoking habit, lower IL-13 serum levels were associated with higher IMT values. CONCLUSIONS: IL-13, an anti-inflammatory cytokine, may have a protective role in the human atherosclerotic process. It could be used as an effective and promising novel therapeutic target development.