Association between Mild Overweight and Survival: A Study of an Exceptionally Long-Lived Population in the Sardinian Blue Zone.

Background/Objectives: Overweight and obesity are generally considered risk factors for premature mortality. However, scientific evidence suggests that among older populations, mild conditions of overweight might be associated with reduced comorbidity and longer survival. This study investigates the potential association between anthropometric parameters and survival among a cohort of nonagenarians in Sardinia, Italy. Methods: This study included 200 subjects (50% females) aged 89 and older, enrolled in 2018 in the Sardinian Blue Zone-a population known for longevity-and followed for up to six years. Anthropometric variables such as body height, weight, age, sex, comorbidity, disability, and food group intake were collected using validated questionnaires and analyzed through multivariable analysis. Results: Out of 200 participants at baseline, 28 (14%) were still alive after six years of follow-up (females 10%, males 18%). Mean survival was 3.36 years (range 0.1-6.9 years) for males and 3.03 years (range 0.2-6.6 years) for females. Participants with a Body Mass Index (BMI) in the range of 25.0-27.0 kg/m2 among males and 25.0-27.2 kg/m2 among females had longer survival compared to those who were underweight (p = 0.002) or obese (p < 0.0001). The Cox proportional hazards regression model, adjusted for age, sex, and comorbidity, revealed a statistically significant association between the BMI and survival, demonstrating an inverted-U relationship. This indicates that mild overweight was associated with a survival advantage compared to both normal weight and obesity. Conclusions: Our study indicates that mild, but not severe, overweight in nonagenarians is associated with extended lifespan. Therefore, primary care physicians and geriatricians should exercise caution before recommending calorie-restricted diets for mildly overweight elderly patients.

The impact of nutrition on psycho-affective status in an older Cretan population: a cross-sectional study.

BACKGROUND: Cognitive and mood status influence both personal and social daily activities, with great impact on life quality, particularly among the elderly population. AIM: This cross-sectional study aimed to investigate the psycho-affective status concerning eating habits within an elderly population of the Chania area in Crete, Greece. METHODS: Cognitive status was assessed in 101 elderly subjects through the Mini-Mental State Examination (MMSE), and mood was evaluated using the Hospital Anxiety and Depression Scale (HADS). Nutritional status was assessed using a validated food frequency questionnaire. RESULTS: Multivariable statistical analysis, after adjustment for age, marital status, education, and comorbidity, highlighted among males a positive association of the MMSE score with vegetable consumption (RR 1.18; 95%CI 1.03‒1.34) and a negative association with potato consumption (RR 0.83; 95%CI 0.72‒0.95). Conversely, among females, no statistically significant association was observed for any food. Further, among males, a protective effect on affective status was identified for chicken meat (RR 0.45; 95%CI 0.27‒0.77), fish (RR 0.41; 95%CI 0.21‒0.82), fruit (RR 0.70; 95%CI 0.52‒0.94), cereals (RR 0.67; 95%CI 0.53‒0.87), and cheese (RR 0.78; 95%CI 0.63‒0.97) consumption. Among females, the adjusted model showed a significant detrimental effect of vegetable consumption (RR 1.33; 95%CI 1.02‒1.73). CONCLUSION: A predominantly vegetable-based diet-with the notable exception of fruits and legumes-was associated with better cognitive status in males, albeit not in females. A higher intake of fruit, as well as fish, chicken meat, and cheese among males was associated with a better affective status, indicating that adequate protein supply may play a role in maintaining emotional balance.

Is a plant-based diet effective to maintain a good psycho-affective status in old age? Results of a survey of a long-lived population from Sardinia.

BACKGROUND: Depression is common among the elderly, resulting in poor quality of life and elevated healthcare expenditure. Among other factors, dietary habits could also affect this condition, although the specific food patterns involved remain to be established. The present study aimed to assess the role of plant- versus animal-dominant foods consumption on the affective state of nonagenarians from a Sardinian population, Italy, well known for its longevity (Blue Zone). METHODS: Data, including demographic, education, anthropometric parameters, monthly income, and comorbidity were recorded and analyzed. Symptomatic depression was assessed using the Geriatric Depression Scale (GDS) during a comprehensive home geriatric assessment; nutritional status was evaluated by a validated food frequency questionnaire. RESULTS: A total of 200 elderly subjects living in the Sardinian Blue Zone (mean age 93.9 ± 3.9 years) participated in the study; symptomatic depression was present in 51% of the whole cohort and was more common among women. Multivariable logistic regression showed a significantly greater risk of depression in people consuming plantbased foods (OR = 1.42, 95% CI 1.04-1.93), whereas moderate animal-derived foods consumption was associated with a better affective state (OR = 0.79, 95% CI 0.62-0.98). CONCLUSIONS: These findings indicate that a more balanced diet, including animal-derived foods, instead of an exclusive plant-dominant diet, may be more appropriate in the elderly, and abstention from animal-based food intake should not be recommended in advanced age to prevent depression.

Risk of Hemolytic Anemia in IBD Patients with Glucose-6-Phosphate Dehydrogenase Deficiency Treated with Mesalamine: Results of a Retrospective-Prospective and Ex Vivo Study.

BACKGROUND: Mesalamine is one of the most-used drugs in inflammatory bowel disease (IBD), especially ulcerative colitis. Regulatory agencies have listed mesalamine as an unsafe drug in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency based on the risk of hemolysis, although scientific evidence is lacking. The occurrence of acute and/or chronic hemolytic anemia in IBD patients with G6PD deficiency exposed to mesalamine was evaluated. METHODS: In this multicenter study, IBD patients with G6PD deficiency (cases) receiving mesalamine were retrospectively evaluated for acute, and prospectively for chronic, hemolysis. The presence of hemolytic anemia was based on red blood cell and reticulocyte count, hemoglobin, lactate dehydrogenase, unconjugated bilirubin, and haptoglobin levels. Cases were compared with controls (IBD patients with normal G6PD). RESULTS: A total of 453 IBD patients (mean age 52.1 ± 16.0 years; 58.5% female) were enrolled. Ulcerative colitis was present in 75% of patients. G6PD deficiency was detected in 17% of patients. Oral mesalamine was used in 67.9% of ulcerative colitis and in 32.4% of Crohn's disease cases. None of the 78 IBD patients with G6PD deficiency receiving mesalamine underwent hospitalization or specific treatment for acute hemolytic anemia. Relevant differences in chronic hemolysis markers were not observed in 30 cases compared with 112 controls receiving mesalamine (≤4500 mg/day). Marker modifications were also observed in mesalamine-free cases, consistent with the basal rate of erythrophagocytosis in G6PD deficiency. Ex vivo experiments showed the release of methemoglobin by G6PD deficient RBCs upon mesalamine challenge, only above 2.5 mg/mL, a concentration never reached in the clinical setting. CONCLUSIONS: This study provides, for the first time, evidence that mesalamine is safe in G6PD deficiency at a dosage of up to 4500 mg/day.

Relationship between Glucose-6-Phosphate Dehydrogenase Deficiency, X-Chromosome Inactivation and Inflammatory Markers.

Recent studies suggest that X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency entails a proinflammatory state that may increase the risk of several disease conditions. However, it is not clear how this relates to the degree of enzyme insufficiency and, in heterozygous females, to skewed inactivation of the X chromosome. This study aimed to (i) investigate the enzyme activity in a cohort of 232 subjects (54.3% females) from Northern Sardinia, Italy, further stratified into three subgroups (G6PD normal, partial deficiency and total deficiency); (ii) measure the levels of some non-specific inflammatory markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and those derived from cell counts, such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR), in relation to the underlying molecular defect and X inactivation. G6PD activity was measured in red blood cells according to G6PD/6PGD ratio, and X-chromosome inactivation was assessed by the HUMARA method. Overall, ESR was increased in males with total deficiency compared with normal males (15.0 ± 7.2 vs. 11.9 ± 6.2, p = 0.002, Tukey's test), albeit not in males with partial deficiency. High-sensitivity CRP was slightly increased in males with total deficiency, compared to males with normal G6PD activity (5.96 ± 3.39 vs. 3.95 ± 2.96, p = 0.048). In females, neither marker showed significant differences across the subgroups. MLR was significantly and progressively increased from normal to totally deficient subjects with intermediate values in partially deficient subjects (0.18, 0.31 and 0.37, ANOVA p = 0.008). The NLR and PLR were not different in the three subgroups. Our findings show that G6PD deficiency may be associated with a proinflammatory profile, especially in elderly females, and worsened by the concomitant asymmetric inactivation of the X chromosome.

High Frequency of Glucose-6-Phosphate Dehydrogenase Deficiency in Patients Diagnosed with Celiac Disease.

Celiac disease (CD) is characterized by a proinflammatory state associated with the production of reactive oxygen species, i.e., a condition of oxidative stress. In this study, we tested the hypothesis that the inherited deficiency of glucose-6-phosphate dehydrogenase (G6PD), by causing impaired antioxidant defense, may increase the risk of CD. METHODS: A retrospective monocentric case-control study was performed using the clinical records of 8338 outpatients (64.6% women) scheduled for upper endoscopy between 2002 and 2021 in Northern Sardinia. Overall, 627 were found to have CD (7.5%), and 1027 resulted to be G6PD-deficiency carriers (12.3%). Since randomization was impractical, the potential covariates imbalance between cases and controls was minimized using a 1:2 propensity-score-matched (PSM) analysis. RESULTS: Overall, G6PD deficiency was associated with increased risk of CD (odds ratio (OR) 1.50; 95% confidence interval (CI) 1.19-1.90). The PSM procedure identified 1027 G6PD-deficient and 2054 normal patients. Logistic regression including the propensity score detected for G6PD deficiency an OR of 1.48 (95%CI 1.13-1.95; p = 0.004). CONCLUSIONS: Our findings show that the enzyme defect was significantly and positively associated with CD, in line with the pro-oxidant impact of the enzyme defect observed in animal models and humans.

Water Quality and Mortality from Coronary Artery Disease in Sardinia: A Geospatial Analysis.

The role of water hardness on human health is still debated, ranging from beneficial to harmful. Before the rise of drinking bottled water, it was a common habit to obtain supplies of drinking water directly from spring-fed public fountains. According to the geographic location, spring waters are characterized by a variable content of mineral components. In this ecological study, for the first time in Sardinia, Italy, the spatial association between spring water quality/composition and standardized mortality ratio (SMR) for coronary artery disease (CAD) in the decade from 1981 to 1991 was investigated using data retrieved from published databases. In a total of 377 municipalities, 9918 deaths due to CAD, including acute myocardial infarction (AMI), ICD-9 code 410, and ischemic heart disease (IHD), ICD-9 code 411-414, were retrieved. A conditional autoregressive model with spatially structured random effects for each municipality was used. The average SMR for CAD in municipalities with a predominantly "soft" (<30 mg/L) or "hard" (≥30 mg/L) water was, respectively, 121.4 ± 59.1 vs. 104.7 ± 38.2 (p = 0.025). More specifically, an inverse association was found between elevated calcium content in spring water and cardiovascular mortality (AMI: r = -0.123, p = 0.032; IHD: r = -0.146, p = 0.009) and borderline significance for magnesium (AMI: r = -0.131, p = 0.054; IHD: r = -0.138, p = 0.074) and bicarbonate (IHD: r = -0.126, p = 0.058), whereas weak positive correlations were detected for sodium and chloride. The lowest CAD mortality was observed in geographic areas (North-West: SMR 0.92; South-East: SMR 0.88), where calcium- and bicarbonate-rich mineral waters were consumed. Our results, within the limitation of an ecological study, confirm the beneficial role of waters with high content in calcium and bicarbonate against coronary artery disease.

Specific features of the oldest old from the Longevity Blue Zones in Ikaria and Sardinia.

Human longevity may be found in single individuals as well as in the population as a whole ("population longevity"). Longevity Blue Zones (LBZs), which are areas with an unusually high number of oldest old, have been identified in Sardinia and the Greek island of Ikaria. We compared the lifestyle, health status and some genetic markers of the LBZ populations with those of reference populations from Italy and Greece; the data were extracted from the GEHA database. In the LBZs, the proportion of individuals who never married or were married and still living with their spouse was significantly greater. Nonagenarians males and females with a high self‒perception of optimism and/or a high score for self-rated health were also found in larger proportions in LBZs. Among the variables with lower frequency were the proportion of the widowed, the percentage of subjects who had suffered a stroke and the frequency of Apoε4 and Apoε2 and the TT genotype of FOXO3A gene. Compared to behavioral and health indicators, the impact of genetic factors might be relatively less important in the LBZs. Nevertheless, further research is needed to identify potential epigenetic traits that might play a predominant role due to the interaction between genetics and the human and physical environments.

Evolution of the Dietary Patterns Across Nutrition Transition in the Sardinian Longevity Blue Zone and Association with Health Indicators in the Oldest Old.

Health and longevity in humans are influenced by numerous factors, including lifestyle and nutrition. However, the direct relationship between lifetime eating habits and functional capacity of the elderly is poorly understood. This study investigated the dietary changes across nutrition transition (NT) in the early 1960s, in a population located in the Sardinia island known for its longevity, dubbed as "Longevity Blue Zone" (LBZ), as well as the relationship between the dietary patterns and a panel of health indicators. A total of 150 oldest-old participants (89 women and 61 men, age range 90-101 years) living in the LBZ were recruited. Participants were interviewed using validated questionnaires to assess the consumption frequency of common food items, as well as the correlation with self-rated health, comorbidity, affective and cognitive level, physical mobility, disability and anthropometric parameters. Differences between subgroups were evaluated using the Mann-Whitney U test for independent samples or the Wilcoxon signed-rank test for paired samples. Correlation analysis was performed by calculating the Spearman correlation coefficient, separately in males and females. Compared to the pre-NT epoch, the consumption of meat, olive oil and fresh fruit slightly increased, while the consumption of lard, legumes and vegetables decreased. A significant association was found between increased olive oil intake across NT and self-rated health (ρ = 0.519), mobility (ρ = 0.502), improved vision (ρ = -0.227) and hearing (ρ = -0.314); increased chicken meat intake and performance in activities of daily living (basic activities of daily living: ρ = 0.351; instrumental activities of daily living: ρ = 0.333). Instead, vegetable consumption showed low correlation with health indicators. A mild increase in meat intake, mostly pastured poultry, is associated with better physical performance in the Sardinian LBZ elders, suggesting that a supply of protein may have been crucial to maintaining adequate functional capacity.

Circulating fatty acids and endocannabinoidome-related mediator profiles associated to human longevity.

To evaluate whether a peculiar plasma profile of fatty acids and endocannabinoidome (eCBome)-related mediators may be associated to longevity, we assessed them in octogenarians (Old; n=42) living in the east-central mountain area of Sardinia, a High-Longevity Zone (HLZ), compared to sexagenarian (Young; n=21) subjects from the same area, and to Olds (n=22) from the Northern Sardinia indicated as Lower-Longevity Zone (LLZ). We found significant increases in conjugated linoleic acid (CLA) and heptadecanoic acid (17:0) levels in Old-HLZ with respect to younger subjects and Old-LLZ subjects. Young-HLZ subjects exhibited higher circulating levels of pentadecanoic acid (15:0) and retinol. Palmitoleic acid (POA) was elevated in both Young and Old subjects from the HLZ. eCBome profile showed a significantly increased plasma level of the two endocannabinoids, N-arachidonoyl-ethanolamine (AEA) and 2-arachidonoyl-glycerol (2-AG) in Old-HLZ subjects compared to Young-HLZ and Old-LLZ respectively. In addition, we found increased N-oleoyl-ethanolamine (OEA), 2-linoleoyl-glycerol (2-LG) and 2-oleoyl-glycerol (2-OG) levels in Old-HLZ group with respect to Young-HLZ (as for OEA an d 2-LG) and both the Old-LLZ and Young-HLZ for 2-OG. The endogenous metabolite of docosahexaenoic acid (DHA), N-docosahexaenoyl-ethanolamine (DHEA) was significantly increased in Old-HLZ subjects. In conclusion, our results suggest that in the HLZ area, Young and Old subjects exhibited a favourable, albeit distinctive, fatty acids and eCBome profile that may be indicative of a metabolic pattern potentially protective from adverse chronic conditions. These factors could point to a suitable physiological metabolic pattern that may counteract the adverse stimuli leading to age-related disorders such as neurodegenerative and metabolic diseases.

Fecal Microbiota Signatures in Celiac Disease Patients With Poly-Autoimmunity.

To date, reliable tests enabling the identification of celiac disease (CD) patients at a greater risk of developing poly-autoimmune diseases are not yet available. We therefore aimed to identify non-invasive microbial biomarkers, useful to implement diagnosis of poly-autoimmunity. Twenty CD patients with poly-autoimmunity (cases) and 30 matched subjects affected exclusively by CD (controls) were selected. All patients followed a varied gluten-free diet for at least 1 year. Fecal microbiota composition was characterized using bacterial 16S ribosomal RNA gene sequencing. Significant differences in gut microbiota composition between CD patients with and without poly-autoimmune disease were found using the edgeR algorithm. Spearman correlations between gut microbiota and clinical, demographic, and anthropometric data were also examined. A significant reduction of Bacteroides, Ruminococcus, and Veillonella abundances was found in CD patients with poly-autoimmunity compared to the controls. Bifidobacterium was specifically reduced in CD patients with Hashimoto's thyroiditis and its abundance correlated negatively with abdominal circumference values in patients affected exclusively by CD. In addition, the duration of CD correlated with the abundance of Firmicutes (negatively) and Odoribacter (positively), whereas the abundance of Desulfovibrionaceae correlated positively with the duration of poly-autoimmunity. This study provides supportive evidence that specific variations of gut microbial taxa occur in CD patients with poly-autoimmune diseases. These findings open the way to future validation studies on larger cohorts, which might in turn lead to promising diagnostic applications.

Dietary Habits, Anthropometric Features and Daily Performance in Two Independent Long-Lived Populations from Nicoya peninsula (Costa Rica) and Ogliastra (Sardinia).

(1) Background: Longevity Blue Zones (LBZs) are populations characterized by exceptional longevity. The purpose of this cross-sectional study was to compare the food habits of two representative samples of the oldest old subjects from the population residing in the LBZs of Nicoya peninsula (Costa Rica) and in the mountainous part of Ogliastra (Sardinia, Italy). (2) Methods: Data were collected using validated tools, including a food frequency questionnaire, Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL) scales for functional autonomy, body mass index, and waist and limbs circumferences. (3) Results: A total of 210 subjects, 60 (31 male) from Nicoya (age range 80‒109 years), and 150 (61 male) from Ogliastra (age 90‒101 years) were included in the study. In both populations, the highest frequencies of consumption were recorded for plant-derived foods (cereals 60‒80% daily, legumes ≥ 80% daily in Nicoya, ≥ 60% 2‒5 servings/week in Ogliastra), followed by those of animal origin (dairy products, meat) ≥ 60% and 80% daily, in Nicoya and Ogliastra, respectively. The frequency of milk consumption showed a positive correlation with BADL (ρ = 0.268 for Nicoya and ρ = 0.214 for Ogliastra) and IADL scores (ρ = 0.466 for Nicoya and ρ = 0.471 for Ogliastra), whereas legumes consumption correlated negatively with self-rated health (ρ = ‒0.264) and IADL (ρ = ‒0.332). (4) Conclusions: Our results indicate that the dominant dietary model among the elderly of Nicoya and Ogliastra is a plant-based diet complemented by a non-negligible consumption of animal products, mostly dairy products. Further prospective studies are needed to ascertain a possible cause‒effect relationship between food habits and increased likelihood of reaching advanced age.

The Rise and Fall of the Secular Trend in Body Height in Sardinia: An Age-Period-Cohort Analysis.

OBJECTIVE: Over the last century, a progressive rise in stature, known as the 'secular trend', was documented worldwide, and especially in Sardinia, it has reached a peak in Europe. However, this situation recently ceased in several populations. In this study, we tested the hypothesis that the stature secular trend has significantly leveled off in the Sardinian younger generations. METHODS: Height measurements were retrieved from a database of patients undergoing digestive endoscopy, spanning generations between 1920 and 1990. Sex-specific principal component regression models were fitted to decompose stature variation into the contribution of age, period, and birth cohort. RESULTS: A steady increase in stature was observed in generations born after 1920, with an upward surge in those born after 1950. However, a significant leveling off was observed among cohorts born after 1970 among both sexes, as mean heights stabilized at 171.1 cm with a standard error (SE) of 0.9 cm among men and a mean of 160.1 cm (SE = 0.9 cm) among women. CONCLUSION: Our findings support a significant slowdown in the secular trend of stature among the latest Sardinian generations. Several factors, including the consumption of low-quality food, lack of physical activity, and late motherhood, among others, may explain the decline in the secular trend.

Is mini-nutritional assessment a reliable tool in detecting malnutrition in elderly with body weight excess?

PURPOSE: The rising proportion of elderly population in high-income societies has resulted in increasing number of subjects with chronic disabling diseases and nutritional deficiency. Elderly's nutritional status is usually assessed through the mini-nutritional assessment (MNA®). However, its effectiveness may be influenced by weight excess or obesity. We tested the performance of MNA® questionnaire in subjects aged ≥ 65 years from Northern Sardinia, Italy, according to overweight/obesity, and we tried to identify the factors associated with malnutrition. METHODS: A modified version of MNA® (mMNA) test, not including BMI, was compared with the conventional MNA® (cMNA) test, and the overall test performance was assessed by calculating sensitivity, specificity and accuracy. In addition, indexes of cognitive health, disability, comorbidity and polypharmacy were compared between patients with concordant and discordant MNA tests. RESULTS: cMNA® sensitivity, specificity and accuracy were 67%, 99% and 84% compared with the mMNA test, due to malnourished patients misclassified as normal because of excess weight. Predictors of malnutrition were: depression (p < 0.0001), disability (p < 0.0001) and polypharmacy (p < 0.0001). Interestingly, the average scores of the "global", "subjective" and "dietary" components of the cMNA®, were significantly lower compared with the corresponding scores of the mMNA. CONCLUSIONS: Excess of weight, a condition progressively rising in the elderly population, may reduce the performance of cMNA® test in detecting malnutrition. LEVEL OF EVIDENCE: Level III, case‒control analytic study.

Sociodemographic, Clinical and Functional Profile of Nonagenarians from Two Areas of Sardinia Characterized by Distinct Longevity Levels.

Introduction: Among the world's longest-lived communities the so-called Longevity Blue Zone (LBZ) of Sardinia, Italy, has attracted a lot of interest. In the present study, health profile and functional characteristics of LBZ oldest-old were compared with an age-matched sample from Northern Sardinia (NSS) with a lower longevity level. Methods: Cognitive status, symptomatic depression, disability, and nutritional status were assessed by standardized instruments. In addition, the proportion of escapers (illness-free medical history), delayers (illness only after age 80), and survivors (at least one disease before age 80) was calculated. Results: Three hundred individuals, 150 from the LBZ (age range 89-101, 89 women), and 150 from NSS (age range 89-101, 101 women) were enrolled. The proportion of married individuals in the LBZ cohort was significantly greater compared with the NSS (55% vs. 32%, p = 0.0001). The educational level among nonagenarians in the LBZ was almost half compared with NSS (p < 0.0001). Unskilled workers, shepherds, and peasants prevailed in the LBZ (79% vs. 21%, p < 0.0001). Institutionalized subjects were 1% in the LBZ and 14% in the NSS (p < 0.0001). Disability, comorbidity, and daily physical activity were more represented in LBZ. There was a significantly higher percentage of delayers (37% vs. 18%, p < 0.0002), and a reduction in the number of survivors (30% vs. 44%, p = 0.012) in the LBZ compared with the NSS group. The proportion of escapers was similar in both groups (33% vs. 38%, n.s.). Conclusion: These findings suggest that in the LBZ there are factors enabling frail individuals to live longer despite a greater burden of comorbidity.

Association of endemic goitre and exceptional longevity in Sardinia: evidence from an ecological study.

This study aims to test the hypothesis that a high prevalence of endemic goitre, considered as a proxy measure for subclinically reduced thyroid function in the population, is geographically associated with exceptional longevity. Using historical data available for 377 Sardinian municipalities in the first half of the twentieth century, we performed an ecological study to investigate the geographic distribution of goitre and its spatial association with demographic indicators of population longevity. This analysis was conducted by using both conventional ordinary least square and geographically weighted regression models to take into account spatial autocorrelation and included other longevity-associated factors previously identified in Sardinia. The spatial analysis revealed that the goitre rate (p < 0.0001), the proportion of inhabitants involved in pastoralism (p = 0.016), the terrain inclination (p = 0.008), and the distance from the workplace as a proxy for physical activity (p = 0.023) were consistently associated with population longevity at an aggregated level in the 377 municipalities. Within the limits of an ecological study design, our findings support the existence of a significant association between high goitre prevalence and increased probability to survive into old age. The present study confirms previous results and is consistent with animal studies and epidemiological surveys in other long-lived areas known as Blue Zones. Potential mechanisms underlying this association need to be further investigated.

TAS2R38 bitter taste receptor and attainment of exceptional longevity.

Bitter taste receptors play crucial roles in detecting bitter compounds not only in the oral cavity, but also in extraoral tissues where they are involved in a variety of non‒tasting physiological processes. On the other hand, disorders or modifications in the sensitivity or expression of these extraoral receptors can affect physiological functions. Here we evaluated the role of the bitter receptor TAS2R38 in attainment of longevity, since it has been widely associated with individual differences in taste perception, food preferences, diet, nutrition, immune responses and pathophysiological mechanisms. Differences in genotype distribution and haplotype frequency at the TAS2R38 gene between a cohort of centenarian and near-centenarian subjects and two control cohorts were determined. Results show in the centenarian cohort an increased frequency of subjects carrying the homozygous genotype for the functional variant of TAS2R38 (PAV/PAV) and a decreased frequency of those having homozygous genotype for the non-functional form (AVI/AVI), as compared to those determined in the two control cohorts. In conclusion, our data providing evidence of an association between genetic variants of TAS2R38 gene and human longevity, suggest that TAS2R38 bitter receptor can be involved in the molecular physiological mechanisms implied in the biological process of aging.

Overweight: A Protective Factor against Comorbidity in the Elderly.

The aim of this study was to investigate the relationship between body mass index (BMI) categories and comorbidity in 9067 patients (age range 18‒94 years) who underwent upper digestive endoscopy in Northern Sardinia, Italy. The majority of participants (62.2%) had a BMI under 25 kg/m2, overweight was detected in 30.4%, and obesity (BMI ≥ 30 kg/m2) in 7.4% of patients. The most frequent illness recorded was hypertension followed by cardiovascular and liver disease. The multivariate analysis, after adjusting for sex, residence, marital status, smoking habits, occupation and hospitalization detected an association between comorbidity and aging that was statistically significant and progressive. Among patients younger than 60 years (n = 5612) the comorbidity risk was higher for BMI ranging 27.5‒29.9 kg/m2 compared with BMI 25.0‒27.4 kg/m2 (RR = 1.38; 95% CI 1.27‒1.50 vs. RR = 0.86; 95% CI 0.81‒0.90). In patients older than 60 years (n= 3455) the risk was lower for a BMI in the range 27.5-29.9 kg/m2 compared with a BMI in the range 25.0-27.4 kg/m2 (RR = 1.11; 95% CI 1.05‒1.18 vs. RR = 1.28; 95% CI 1.21‒1.35). These results suggest that being moderately overweight is a marker of a healthy aging process and might protect, at least in part, against comorbidity. However, further research is needed to better understand this unexpected finding.

Glucose-6-phosphate dehydrogenase deficiency reduces susceptibility to cancer of endodermal origin.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited enzyme defect worldwide. There is a growing scientific evidence for a protective role of G6PD deficiency against carcinogenesis. In this retrospective analysis, we tested the hypothesis that G6PD deficiency may reduce the risk of developing cancer in a tissue-specific manner. Material and methods: The study was conducted using data from 11,708 subjects undergoing gastrointestinal endoscopic procedures between 2002 and 2018 and tested for G6PD status in a teaching hospital of Northern Sardinia, Italy. Results: A 40% reduction of risk for cancer of endodermal origin was observed among G6PD-deficient patients compared with subjects with normal enzyme activity (relative risk (RR) 0.61, 95% confidence interval (CI) 0.47-0.80) in both genders, confirmed by multivariable generalized linear regression after adjusting for age, sex, smoking habits, body mass index, diabetes and socio-economic status. The 'protective' effect of G6PD deficiency was larger for gastric cancer (RR 0.41, 95% CI 0.18-0.99), hepatocellular carcinoma (RR 0.48, 95% CI 0.26-0.92) and colorectal cancer (RR 0.72, 95% CI 0.53-0.98), while a non-significant risk was observed for breast, prostate, lung, hematopoietic and metastases (primary site unknown). Conclusions: Our results suggest a reduced susceptibility to develop cancers, mostly of endodermal origin (stomach, colon and liver), but not of ectodermal/mesodermal origin, in carriers of G6PD deficiency. The effects of G6PD deficiency on carcinogenesis need further studies to better understand how cancer cells originating from different germ layers use pentose phosphate pathway to proliferate.