Humoral immunity induced by mRNA COVID-19 vaccines in Nursing Home Residents previously infected with SARS-CoV-2.

BACKGROUND: Nursing home (NH) residents suffered the greatest impact of the COVID-19 pandemic. Limited data are available on vaccine-induced immunity and on the protection ensured by a prior infection in this population. AIMS: The present study aims to monitor antibody levels and their persistence over a 6-month period in NH residents according to the history of prior SARS-CoV-2 infection. METHODS: We measured anti-trimeric Spike IgG antibody levels in a sample of 395 residents from 25 NHs in 6 Italian Regions at study enrolment (prior to the first dose of vaccine, T0) and then after 2 (T1) and 6 months (T2) following the first vaccine dose. All participants received mRNA vaccines (BNT162b2 or mRNA-1273). Analyses were performed using log-transformed values of antibody concentrations and geometric means (GM) were calculated. RESULTS: Superior humoral immunity was induced in NH residents with previous SARS-CoV-2 infection. (T0: GM 186.6 vs. 6.1 BAU/ml, p < 0.001; T1: GM 5264.1 vs. 944.4 BAU/ml, p < 0.001; T2: GM 1473.6 vs. 128.7 BAU/ml, p < 0.001). Residents with prior SARS-CoV-2 infection receiving two vaccine doses presented significantly higher antibody concentration at T1 and T2. A longer interval between previous infection and vaccination was associated with a better antibody response over time. DISCUSSION: In a frail sample of NH residents, prior SARS-CoV-2 infection was associated with a higher humoral response to vaccination. Number of vaccine doses and the interval between infection and vaccination are relevant parameters in determining humoral immunity. CONCLUSIONS: These findings provide important information to plan future immunization policies and disease prevention strategies in a highly vulnerable population.

The Report-AGE project: a permanent epidemiological observatory to identify clinical and biological markers of health outcomes in elderly hospitalized patients in Italy.

BACKGROUND: Italy is expected to experience the largest growth in persons ≥65 years (>20% by 2020). This demographic shift allows for geriatric research on predictive clinical and biological markers of outcomes related to frailty, re-hospitalization and mortality. AIMS: To describe rationale and methods of the Report-AGE study project of acute care patients in Italian National Research Center on Aging (INRCA) research hospitals. METHODS: Report-AGE study is a large observational study on health conditions and outcomes of hospitalized elderly patients (≥65 years). The primary objective of the study is to create a high-level data resource of demographics, comprehensive geriatric assessments, clinical and diagnostic information, as well as biological and molecular markers in all older patients admitted to INRCA Hospitals. Assessments in physical and nutritional parameters, co-morbid health conditions, and associations with frailty parameters are ongoing in older hospitalized adults following an acute event. Study collection began in September 2011. RESULTS: Up to date, there are 3479 patients ≥65 years (mean age: 85 ± 7years) with 1543 men and 1936 women enrolled. Data have been recorded regarding functional and clinical parameters before, during hospital admission and at discharge. Data collection for primary outcome analyses related to re-hospitalization and mortality is estimated for September 2016. DISCUSSION: This study aims at collecting precise clinical data, comprehensive geriatric assessment, risk factors, and biological data from acute care patients. Data will also be used to identify mechanisms underlying frailty in this specific population. CONCLUSION: This study provides a descriptive epidemiological collection of the health conditions of older in-patients.

Body composition markers in older persons with COPD.

BACKGROUND: Body composition has been shown to be correlated with physical performance, but data in older persons with diverse chronic diseases are lacking. OBJECTIVE: We aimed at investigating the associations of body composition to gait speed and nutritional status of older people in different stages of chronic obstructive pulmonary disease (COPD). DESIGN, SETTING AND SUBJECTS: Cross-sectional analysis of data from Pulmonary Rehabilitation Geriatric Unit at INRCA in Casatenovo, Italy including 132 consecutively admitted COPD patients (mean age: 75 years) with data on body composition, walking speed and respiratory parameters. METHODS: Body mass parameters were assessed using bioelectrical impedance analysis. Pulmonary function tests included spirometry and arterial blood gases. Differences among body composition markers were compared according to gender. Separate multivariate linear regression models with gait speed as the dependent variable were used to test for independent associations with body composition markers after adjusting for multiple confounders. RESULTS: Walking speed deteriorated with increasing severity of COPD. Men were heavier and had more lean mass than women. Participants in the fastest gait tertile were younger, had lower body mass index and fat mass (FM); higher lean-to-fat ratio and albumin levels and better respiratory function (FEV1, FVC) compared with those in the slower tertiles. Total body FM was an independent determinant of walking speed, while fat-free mass and lean-to-fat ratio were not. CONCLUSIONS: Excess body fat may be harmful for physical functioning among elders with COPD.

Circulating biomarkers of inflammaging and Alzheimer's disease to track age-related trajectories of dementia: Can we develop a clinically relevant composite combination?

Alzheimer's disease (AD) is a rapidly growing global concern due to a consistent rise of the prevalence of dementia which is mainly caused by the aging population worldwide. An early diagnosis of AD remains important as interventions are plausibly more effective when started at the earliest stages. Recent developments in clinical research have focused on the use of blood-based biomarkers for improve diagnosis/prognosis of neurodegenerative diseases, particularly AD. Unlike invasive cerebrospinal fluid tests, circulating biomarkers are less invasive and will become increasingly cheaper and simple to use in larger number of patients with mild symptoms or at risk of dementia. In addition to AD-specific markers, there is growing interest in biomarkers of inflammaging/neuro-inflammaging, an age-related chronic low-grade inflammatory condition increasingly recognized as one of the main risk factor for almost all age-related diseases, including AD. Several inflammatory markers have been associated with cognitive performance and AD development and progression. The presence of senescent cells, a key driver of inflammaging, has also been linked to AD pathogenesis, and senolytic therapy is emerging as a potential treatment strategy. Here, we describe blood-based biomarkers clinically relevant for AD diagnosis/prognosis and biomarkers of inflammaging associated with AD. Through a systematic review approach, we propose that a combination of circulating neurodegeneration and inflammatory biomarkers may contribute to improving early diagnosis and prognosis, as well as providing valuable insights into the trajectory of cognitive decline and dementia in the aging population.

Efficacy of OM-85 in Recurrent Respiratory Tract Infections.

BACKGROUND: In older patients, prevention of acute respiratory tract infections (RTIs) is challenging. Experimental studies have consistently underlined an immune-potentiating effect of the bacterial lysates product OM85, on both cellular and humoral responses. OBJECTIVE: This work aimed to assess the potential efficacy of OM-85 for RTIs' prevention in older individuals. METHODS: This explorative longitudinal study included 24 patients aged 65 years or older recruited in the GeroCovid Observational Study- home and outpatient care cohort. For the study purposes, we included 8 patients treated with OM-85 from December 2020 to June 2021 (group A), and a control group of 16 patients, matched for sex and age, who did not receive bacterial lysates (group B). RTIs were recorded from the participants' medical documentation in an e-registry from March 2020 to December 2021. RESULTS: In 2020, group A experienced a total of 8 RTIs, which affected 6 out of 8 patients (75%); group B reported 21 RTIs, with at least one event in 11 out of 16 patients (68.7%). In 2021, RTIs affected 2 out of 8 patients (25%) in group A (p < 0.02), and 13 out of 16 patients (81.2%) in group B (within this group, 5 patients had two RTIs). The RTIs' cumulative incidence over the observation period significantly differed between groups (66.7% in group A vs. 24.3% in group B; p < 0.002), as well as the decrease in RTIs frequency from 2020 to 2021. No patients in group A were affected by COVID-19 during the observation period, while among controls, two patients had SARS-CoV-2 infection, notwithstanding three doses of vaccine. CONCLUSION: This study suggests that bacterial lysates may provide clinical benefits for preventing RTIs. Additional research involving larger cohorts is required to verify the effectiveness of OM-85 in preventing RTIs in older adults.

Clinical profile of trazodone users in a multisetting older population: data from the Italian GeroCovid Observational study.

BACKGROUND AND OBJECTIVES: Depression is highly prevalent in older adults, especially in those with dementia. Trazodone, an antidepressant, has shown to be effective in older patients with moderate anxiolytic and hypnotic activity; and a common off-label use is rising for managing behavioral and psychological symptoms of dementia (BPSD). The aim of the study is to comparatively assess the clinical profiles of older patients treated with trazodone or other antidepressants. METHODS: This cross-sectional study involved adults aged ≥ 60 years at risk of or affected with COVID-19 enrolled in the GeroCovid Observational study from acute wards, geriatric and dementia-specific outpatient clinics, as well as long-term care facilities (LTCF). Participants were grouped according to the use of trazodone, other antidepressants, or no antidepressant use. RESULTS: Of the 3396 study participants (mean age 80.6 ± 9.1 years; 57.1% females), 10.8% used trazodone and 8.5% others antidepressants. Individuals treated with trazodone were older, more functionally dependent, and had a higher prevalence of dementia and BPSD than those using other antidepressants or no antidepressant use. Logistic regression analyses found that the presence of BPSD was associated with trazodone use (odds ratio (OR) 28.4, 95% confidence interval (CI) 18-44.7 for the outcome trazodone vs no antidepressants use, among participants without depression; OR 2.17, 95% CI 1.05-4.49 for the outcome trazodone vs no antidepressants use, among participants with depression). A cluster analysis of trazodone use identified three clusters: cluster 1 included mainly women, living at home with assistance, multimorbidity, dementia, BPSD, and depression; cluster 2 included mainly institutionalized women, with disabilities, depression, and dementia; cluster 3 included mostly men, often living at home unassisted, with better mobility performance, fewer chronic diseases, dementia, BPSD, and depression. DISCUSSION: The use of trazodone was highly prevalent in functionally dependent and comorbid older adults admitted to LTCF or living at home. Clinical conditions associated with its prescription included depression as well as BPSD.

Sex differences in the efficacy and safety of SARS-CoV-2 vaccination in residents of long-term care facilities: insights from the GeroCovid Vax study.

Despite the reported sex-related variations in the immune response to vaccination, whether the effects of SARS-CoV-2 vaccination differ by sex is still under debate, especially considering old vulnerable individuals, such as long-term care facilities (LTCFs) residents. This study aimed to evaluate COVID-19 infections, adverse events, and humoral response after vaccination in a sample of LTCF residents. A total of 3259 LTCF residents (71% females; mean age: 83.4 ± 9.2 years) were enrolled in the Italian-based multicenter GeroCovid Vax study. We recorded the adverse effects occurring during the 7 days after vaccine doses and COVID-19 cases over 12 months post-vaccination. In a subsample of 524 residents (69% females), pre- and post-vaccination SARS-CoV-2 trimeric S immunoglobulin G (Anti-S-IgG) were measured through chemiluminescent assays at different time points. Only 12.1% of vaccinated residents got COVID-19 during the follow-up, without any sex differences. Female residents were more likely to have local adverse effects after the first dose (13.3% vs. 10.2%, p = 0.018). No other sex differences in systemic adverse effects and for the following doses were recorded, as well as in anti-S-IgG titer over time. Among the factors modifying the 12-month anti-S-IgG titers, mobility limitations and depressive disorder were more likely to be associated with higher and lower levels in the antibody response, respectively; a significantly lower antibody titer was observed in males with cardiovascular diseases and in females with diabetes or cognitive disorders. The study suggests that, among LTCF residents, SARS-CoV-2 vaccination was effective regardless of sex, yet sex-specific comorbidities influenced the antibody response. Local adverse reactions were more common in females.

Efficacy of COVID-19 control measures on post-vaccination outbreak in Italian Long Term Care Facilities: implications for policies.

Background: Numerous individual and organizational factors can influence the spread of SARS-CoV-2 infection in Long Term Care Facilities (LTCFs). A range of outbreak control measures are still implemented in most facilities involving administrations, staff, residents and their families. This study aims to evaluate which measure could influence the transmission of SARS-CoV-2 infection among residents during the period March 2021-June 2022. Methods: We enrolled 3,272 residents aged ≥60 years. The outbreak control measures adopted to prevent or manage the infection included entry regulations, contact-regulating procedures, and virological surveillance of residents and staff. The association between LTCFs' and participants' characteristics with new cases of COVID-19 infections was analyzed using multilevel logistic regression models. Results: In 33.8% of the facilities 261 cases of SARS-CoV-2 infection were reported. Among participant characteristics, gender and age were not associated with SARS-CoV-2 infection, while having received the vaccine booster dose was protective against infection [Odds Ratio (OR) = 0.34, 95% Confidence Interval (CI) 0.12-0.99, p = 0.048]. In addition, the implementation of protected areas for family visits was associated with a significant reduction of the probability of infections (OR = 0.18, 95% CI 0.03-0.98, p = 0.047). Overall, about 66% of the variability in the probability of SARS-CoV-2 infection during the observational period may be due to facility structure characteristics and 34% to the participant characteristics. Conclusions: These data showed that vaccination booster doses and family visit restriction-control are still needed to make the LTCFs safer against SARS-CoV-2 infection.

Monitoring COVID-19 vaccine use in Italian long term care centers: The GeroCovid VAX study.

The COVID-19 pandemic has changed routine care practice for older persons, especially in those with frailty living in long term care (LTC) facilities. Due to the high mortality rates of Nursing home (NH) residents during the first wave of the COVID-19 pandemic, priority for COVID-19 vaccinations was given to this vulnerable population. However, the safety and efficacy of such vaccines in older frail elders remains questionable due to the fact that initial randomized clinical trials (RCTs) for such vaccines did not include this population. This type of discrimination in patient participation in RCTs continues and has been recognized in the literature. Nevertheless, in the context of a worldwide emergency, COVID-19 vaccination in older persons living in LTC facilities may provide a solid basis to protect against negative outcomes, such as COVID-19 infection and death. In this report, we present the protocol of the GeroCovid Vax study, an Italian study that began in February 2021 which is aimed at investigating the safety and efficacy of the anti-SARS-CoV-2 vaccinations in older persons living in LTCs. This protocol specially aims to continuously and closely monitor events related to- and following- the anti-SARS-CoV-2 vaccination in elderly living in LTC facilities. In this report, we will provide information related to the study protocol and describe baseline characteristics of the sample.

Targeting inflammation to slow or delay functional decline: where are we?

The role of inflammation in the pathophysiology of chronic age-related diseases is increasingly recognized, and inflammation could represent the common pathway linking diseases and disability. Thus, targeting inflammation could represent a useful strategy at preventing or delaying functional decline. In this paper we review recent evidence suggesting that selected drugs, such as statins, fibrates, angiotensin converting enzyme-inhibitors and angiotensin receptor blockers, and physical exercise may be able to contrast functional decline by blunting inflammation. Results from randomized trials investigating the effects of physical activity programs on inflammation and functional decline is still limited, and further investigations are warranted.

Evidence for anti-inflammatory effects of combined administration of vitamin E and C in older persons with impaired fasting glucose: impact on insulin action.

OBJECTIVE: Vitamin E and C given separately improve insulin sensitivity due to an inhibitory effect on oxidative stress and inflammation, however their combined effect on glucose control and inflammation is unknown. To investigate combined effect of Vitamin E and C in elderly with Impaired Fasting Glucose (IFG) on insulin action and substrate oxidation. DESIGN: Controlled-trial administration of Vitamin E (1000 mg/day) and Vitamin C (1000 UI/day) for four weeks. Hyperinsulinemic euglycemic glucose clamp was performed before and following supplementation. SETTING: Out-patient clinic. PARTICIPANTS: Thirteen older men with IFG. MAIN OUTCOME PARAMETERS: Variations in whole body glucose disposal (WBGD), anti-oxidant, and inflammatory cytokines plasma levels. RESULTS: An increase in plasma Vitamin E (8.3 + 0.8 vs. 64.9 + 2.1 micromol/l; p < 0.001] and C (35.9 + 5.4 vs. 79.4 + 7.4 micromol/l; p < 0.001) was found. Vitamin administration reduced insulin, glucose, lipid, TNF-alpha and [8-]isoprostane levels. Increase in plasma vitamin E levels correlated with decline in both plasma [8-]isoprostane levels (r = -0.58; p = 0.048) and TNF-alpha levels (r = - 0.62; p = 0.025), while no correlations were found for Vitamin C. Whole body glucose disposal (WBGD) (22.7 + 0.6 vs. 30.4 + 0.8 mmol x kg-1 x min-1; p = 0.001) and non-oxidative glucose metabolism rose after supplementation. Rise in plasma levels of Vitamin C and E correlated with WBGD. Multivariate linear regression models showed independent associations among the change in Vitamin E and the decline in TNF-alpha and [8-]isoprostane levels. CONCLUSIONS: Combined administration of Vitamin E and C lowered inflammation and improved insulin action through a rise in non-oxidative glucose metabolism.

Repaglinide administration improves brachial reactivity in type 2 diabetic patients.

OBJECTIVE: Several studies have demonstrated that endothelial dysfunction plays a central role in diabetic mortality and that the prooxidative effect of postprandial hyperglycemia may actively contribute to atherogenesis. Thus, we investigated the possible effect of short-acting (repaglinide) and long-acting (glibenclamide) insulin secretagogues on endothelial function in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Sixteen type 2 diabetic patients undergoing diet treatment and with poor glucose control volunteered for the study. The study was designed as a 4-month, randomized, cross-over, parallel-group trial of repaglinide (1 mg twice a day) versus glibenclamide (5 mg twice a day). All patients underwent the following investigations: 1) anthropometrics determinations, 2) blood sampling for routine laboratory analyses and for assessment of oxidative stress indexes, and 3) a brachial reactivity test to evaluate the endothelial function through the study of arterial diameter and flow changes with and without intraarterial infusion of N(G)-monomethyl-l-arginine, an inhibitor of nitric oxide synthase and tetraethylammonium chloride (TEA), a Ca(2+)-activated K(+) (K(Ca)) channel blocker. All patients were randomly assigned to receive repaglinide or glibenclamide for a period of 4 weeks. RESULTS: Repaglinide administration was associated with a significant reduction in 2-h plasma glucose levels (P < 0.001) and in plasma thiobarbituric acid-reactive substances (TBARS) concentrations (P < 0.001) and with a significant increase in plasma antioxidant power, assessed as Trolox equivalent antioxidant capacity (TEAC) (P < 0.001), effects not observed after glibenclamide administration. With regard to brachial reactivity parameters, repaglinide but not glibenclamide was associated with a significant improvement in brachial reactivity parameters (P < 0.003 for all parameters). In contrast, intra-arterial infusion of L-NMMA and TEA reduced the beneficial effect of repaglinide. CONCLUSIONS: Repaglinide administration, through good control of postprandial glucose levels, improves brachial reactivity and declines oxidative stress indexes.

Insulin resistance in cognitive impairment: the InCHIANTI study.

OBJECTIVE: To test the association between cognitive impairment, with and without subcortical features, and insulin resistance in an elderly community-dwelling population. DESIGN: Cross-sectional wave of an epidemiologic longitudinal study (InCHIANTI). PARTICIPANTS: A total of 523 people, aged 70 to 90 years without diabetes mellitus or hyperglycemia, from the InCHIANTI cohort were included in the study. A total of 119 individuals had cognitive impairment (Mini-Mental State Examination [MMSE] score < 25), 21 of whom had both cognitive impairment and subcortical features (CI/SF+ group). Control groups contained 23 individuals with a history of stroke and 381 individuals with no cognitive impairment (no CI group, MMSE score > or = 25). Indicators of insulin resistance were the fasting plasma insulin level, insulin resistance index (Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]), and insulin sensitivity index (Quantitative Insulin Sensitivity Check Index [QUICKI]). RESULTS: The insulin resistance profile of patients in the CI/SF+ group was similar to that of individuals who had experienced stroke, whereas the profile of individuals with cognitive impairment without subcortical features (CI/SF- group) was similar to that of individuals in the no CI group. Patients in the CI/SF- group showed insulin resistance comparable to individuals in the no CI group (age-adjusted P = .27, .19, and .64, respectively, for difference in fasting blood insulin level, HOMA-IR, and QUICKI in linear regression models) and lower than patients with stroke (age-adjusted P = .01, .02, and .07, respectively). On the contrary, patients in the CI/SF+ group had insulin resistance and sensitivity values similar to those of the stroke group (age-adjusted P = .80, .84, and .75, respectively, for difference in fasting blood insulin level, HOMA-IR, and QUICKI) but significantly different from those in the no CI group (age-adjusted P = .01, .03, and .02, respectively). CONCLUSIONS: Cognitive impairment with but not without subcortical features is associated with biochemical and clinical features of insulin resistance syndrome. In epidemiologic populations, insulin resistance might contribute to cognitive impairment through a vascular mechanism.

Treating sarcopenia in older and oldest old.

The presence of sarcopenia is not only rapidly rising in geriatric clinical practice and research, but is also becoming a significant concept in numerous medical specialties. This rapidly rising concept has encouraged the need to identify methods for treating sarcopenia. Physical activity measures using resistance training exercise, combined with nutritional interventions (protein and amino acid supplementation) have shown to significantly improve muscle mass and strength in older persons. Moreover, resistance training may improve muscle strength and mass by improving protein synthesis in skeletal muscle cells. Aerobic exercise has also shown to hold beneficial impacts on sarcopenia by improving insulin sensitivity. At the moment, the literature indicates that most significant improvement in sarcopenia is based on exercise programs. Thus, this type of intervention should be implemented in a persistent manner over time in elders, with or at risk of muscle loss. At the same time, physical training exercise should include correcting nutritional deficits with supplementation methods. For example, in older sarcopenic patients with adequate renal function, daily protein intake should be increased to >1. 0 grams of protein per kilogram of body weight. In particular, leucine, - hydroxy ß-methylbutyrate (HMB), creatine and some milk-based proteins have been shown to improve skeletal muscle protein balance. In addition, it is also recommended for adjustment of for vitamin D deficiency, if present, considering the crucial role of vitamin D in the skeletal muscle. In this review, we provide evidence regarding the effects of different physical exercise protocols, specific nutritional intervention, and some new metabolic agents (HMB, citrulline malate, ornithine, and others) on clinical outcomes related to sarcopenia in older adults.

Severe hypoglycemia is associated with antidiabetic oral treatment compared with insulin analogs in nursing home patients with type 2 diabetes and dementia: results from the DIMORA study.

OBJECTIVES: Severe hypoglycemia is associated with cognitive decline and dementia in older persons with type 2 diabetes. The role of antidiabetic treatments on severe hypoglycemia is unknown in dementia. The aims were to determine the prevalence of severe hypoglycemic events and investigate associations among severe hypoglycemic and specific antidiabetic treatments (classes of oral agents and types of insulin analogs) in a large sample of nursing home patients with diabetes according to dementia status. DESIGN: Cross-sectional observational study. SETTING: A total of 150 nursing homes across Italy. PARTICIPANTS: A total of 2258 patients with type 2 diabetes (dementia = 1138, no dementia = 1120). MEASUREMENTS: Diagnosis of dementia before nursing home admission. Data were collected regarding functional status, glycemic control, antidiabetic treatments, comorbidities, and biochemical and clinical measurements. Logistic regression models with severe hypoglycemia as the dependent variable were used to test associations with antidiabetic agents. RESULTS: Patients had a mean age (SD) of 82 (8) years, body mass index (BMI) of 25.4 (4.8), fasting plasma glucose (FPG) of 7.5 (3.0) mmol/L, postprandial glucose (PPG) of 10.3 (3.6) mmol/L, HbA1c of 7.1% (54 mmol/L), and impairments in activities of daily living (ADLs) of 3.7 (2.1). Severe hypoglycemia was more prevalent in patients with dementia (18%) compared with patients without dementia (8%). Patients with dementia were older, showed greater ADL impairments, greater number of comorbidities, lower FPG, and higher PPG compared with those without dementia. Adjusted logistic regression models in patients with dementia showed that rapid- and long-acting insulin analogs were associated with reduced odds ratio (OR) (OR 0.333; 95% confidence interval [CI] 0.184-0.602; OR 0.248, 95% CI 0.070-0.882, respectively), whereas sulphonylureas and combined metformin + sulphonylurea were associated with increased ORs (OR 8.805, 95% CI 4.260-18.201; OR 6.639; 95% CI 3.273-14.710, respectively) of experiencing severe hypoglycemia. No correlations were found in patients without dementia. CONCLUSION: In older nursing home patients with type 2 diabetes, severe hypoglycemia was significantly higher in dementia. Our findings suggest that sulphonylureas should be used with caution, whereas rapid- and long-acting insulin analogs seem safer.

An international definition for "nursing home".

There is much ambiguity regarding the term "nursing home" in the international literature. The definition of a nursing home and the type of assistance provided in a nursing home is quite varied by country. The International Association of Gerontology and Geriatrics and AMDA foundation developed a survey to assist with an international consensus on the definition of "nursing home."

Glucose regulation and oxidative stress in healthy centenarians.

Aging, oxidative stress and insulin resistance are strongly correlated. There is a growing body of evidence showing that aging is associated with a significant rise in oxidative stress mainly due to a decline in anti-oxidant activity and a rise in pro-oxidant factors such as glucose and insulin concentrations. Furthermore, aging is also associated with a progressive rise in insulin resistance which is due to a complex network of environmental, anthropometric and neuro-hormonal factors. It is noteworthy that extreme longevity, e.g. centenarians, is associated with a low degree of oxidative stress and insulin resistance. The causes for such differences between aged subjects and centenarians is not fully understood. It is likely that a specific genetic background might play a role. However, the insulin gene does not seem to be involved for explaining such age-related differences.