Long-term intensive endurance exercise training is associated to reduced markers of cellular senescence in the colon mucosa of older adults.

Regular endurance exercise training is an effective intervention for the maintenance of metabolic health and the prevention of many age-associated chronic diseases. Several metabolic and inflammatory factors are involved in the health-promoting effects of exercise training, but regulatory mechanisms remain poorly understood. Cellular senescence-a state of irreversible growth arrest-is considered a basic mechanism of aging. Senescent cells accumulate over time and promote a variety of age-related pathologies from neurodegenerative disorders to cancer. Whether long-term intensive exercise training affect the accumulation of age-associated cellular senescence is still unclear. Here, we show that the classical senescence markers p16 and IL-6 were markedly higher in the colon mucosa of middle-aged and older overweight adults than in young sedentary individuals, but this upregulation was significantly blunted in age-matched endurance runners. Interestingly, we observe a linear correlation between the level of p16 and the triglycerides to HDL ratio, a marker of colon adenoma risk and cardiometabolic dysfunction. Our data suggest that chronic high-volume high-intensity endurance exercise can play a role in preventing the accumulation of senescent cells in cancer-prone tissues like colon mucosa with age. Future studies are warranted to elucidate if other tissues are also affected, and what are the molecular and cellular mechanisms that mediate the senopreventative effects of different forms of exercise training.

Circulating eosinophil levels and lung function decline in stable chronic obstructive pulmonary disease: a retrospective longitudinal study. / Níveis de eosinófilos circulantes e declínio da função pulmonar em doença pulmonar obstrutiva crônica estável: um estudo longitudinal retrospectivo.

OBJECTIVE: Whether blood eosinophils (bEOS) in chronic obstructive pulmonary disease (COPD) are associated with disease progression is a topic of debate. We aimed to evaluate whether the differential white blood cell (WBC) count, symptoms and treatment may predict lung function decline and exacerbations in COPD patients. METHODS: We retrospectively examined stable COPD patients with a minimum follow-up of 3 years at our outpatients' clinic. We collected information about lung volumes (FEV1, FVC), the total and differential WBC count, acute exacerbations of COPD (number in the 12 months before the beginning of the study=AE-COPD-B, and during the follow-up=AE-COPD-F), smoking status and treatment. FEV1 decline and AE-COPD-F were described by using a generalized linear model and a 2-level random intercept negative binomial regression, respectively. The models included eosinophil and neutrophil counts as potential predictors and were adjusted by sex, age, smoking status, AE-COPD-B, treatment with bronchodilators and inhaled corticosteroids (ICS). RESULTS: Sixty-eight patients were considered, 36 bEOS- (<170 cells/µL, the median value) and 32 bEOS+ (≥170 cells/µL). ∆FEV1 was higher in bEOS+ than bEOS- (34.86 mL/yr vs 4.49 mL/yr, p=0.029). After adjusting for potential confounders, the eosinophil count was positively (ß=19.4; CI 95% 2.8, 36.1; p=0.022) and ICS negatively (ß=-57.7; CI 95% -91.5,-23.9; p=0.001) associated with lung function decline. bEOS were not found to be associated with the number of AE-COPD-F. CONCLUSION: In stable COPD patients, a higher level of blood eosinophils (albeit in the normal range) predicts a greater FEV1 decline, while ICS are associated with a slower progression of airflow obstruction.

OBJETIVO: Discute-se se eosinófilos no sangue (EOS) na doença pulmonar obstrutiva crônica (DPOC) são associados à evolução da doença. O objetivo deste estudo foi avaliar se a contagem diferencial de células brancas do sangue (CBS), os sintomas e o tratamento podem prever o declínio da função pulmonar e as exacerbações em pacientes com DPOC. MÉTODOS: Foram retrospectivamente examinados pacientes com DPOC estável submetidos a um monitoramento mínimo de três anos em nossas clínicas ambulatoriais. Coletaram-se informações sobre volumes pulmonares (VEF1 e CVF), contagens total e diferencial de CBS, exacerbações agudas de DPOC (número nos 12 meses anteriores ao início do estudo = EA-DPOC-B; e durante o monitoramento = EA-DPOC-F), status tabagístico e tratamento. Os declínios de VEF1 e EA-DPOC-F foram descritos empregando modelo linear generalizado e regressão binomial negativa com interceptação aleatória de nível 2, respectivamente. Os modelos incluíram contagens de eosinófilo e neutrófilo como potenciais preditores e foram ajustados de acordo com sexo, idade, status tabagístico, EA-DPOC-B, tratamento com broncodilatadores e corticosteroides inalados (CSI). RESULTADOS: 68 pacientes foram considerados, dos quais 36 para EOS- (< 170 células/µL, valor da mediana) e 32 para EOS+ (≥ 170 células/µL). ∆VEF1 foi maior em EOS+ do que em EOS- (34,86 mL/ano vs 4,49 mL/ano, p = 0,029). Após o ajuste em relação aos potenciais confundidores, as contagens de eosinófilos (ß = 19,4; CI 95% 2,8,36,1; p = 0,022) e CSI (ß = -57,7; CI 95% -91,5,-23,9; p = 0,001) foram positivamente e negativamente associadas ao declínio da função pulmonar, respectivamente. Os EOS não foram associados ao número de EA-DPOC-F. CONCLUSÃO: Em pacientes com DPOC estável, o maior nível de EOS (embora em um intervalo regular) prevê um maior declínio de VEF1, enquanto os CSIs são associados a uma evolução mais lenta da obstrução do fluxo aéreo.

Níveis de eosinófilos circulantes e declínio da função pulmonar em doença pulmonar obstrutiva crônica estável: um estudo longitudinal retrospectivo / Circulating eosinophil levels and lung function decline in stable chronic obstructive pulmonary disease: a retrospective longitudinal study

RESUMO Objetivo Discute-se se eosinófilos no sangue (EOS) na doença pulmonar obstrutiva crônica (DPOC) são associados à evolução da doença. O objetivo deste estudo foi avaliar se a contagem diferencial de células brancas do sangue (CBS), os sintomas e o tratamento podem prever o declínio da função pulmonar e as exacerbações em pacientes com DPOC. Métodos Foram retrospectivamente examinados pacientes com DPOC estável submetidos a um monitoramento mínimo de três anos em nossas clínicas ambulatoriais. Coletaram-se informações sobre volumes pulmonares (VEF1 e CVF), contagens total e diferencial de CBS, exacerbações agudas de DPOC (número nos 12 meses anteriores ao início do estudo = EA-DPOC-B; e durante o monitoramento = EA-DPOC-F), status tabagístico e tratamento. Os declínios de VEF1 e EA-DPOC-F foram descritos empregando modelo linear generalizado e regressão binomial negativa com interceptação aleatória de nível 2, respectivamente. Os modelos incluíram contagens de eosinófilo e neutrófilo como potenciais preditores e foram ajustados de acordo com sexo, idade, status tabagístico, EA-DPOC-B, tratamento com broncodilatadores e corticosteroides inalados (CSI). Resultados 68 pacientes foram considerados, dos quais 36 para EOS- (< 170 células/μL, valor da mediana) e 32 para EOS+ (≥ 170 células/μL). ∆VEF1 foi maior em EOS+ do que em EOS- (34,86 mL/ano vs 4,49 mL/ano, p = 0,029). Após o ajuste em relação aos potenciais confundidores, as contagens de eosinófilos (β = 19,4; CI 95% 2,8,36,1; p = 0,022) e CSI (β = -57,7; CI 95% -91,5,-23,9; p = 0,001) foram positivamente e negativamente associadas ao declínio da função pulmonar, respectivamente. Os EOS não foram associados ao número de EA-DPOC-F. Conclusão Em pacientes com DPOC estável, o maior nível de EOS (embora em um intervalo regular) prevê um maior declínio de VEF1, enquanto os CSIs são associados a uma evolução mais lenta da obstrução do fluxo aéreo.

ABSTRACT Objective Whether blood eosinophils (bEOS) in chronic obstructive pulmonary disease (COPD) are associated with disease progression is a topic of debate. We aimed to evaluate whether the differential white blood cell (WBC) count, symptoms and treatment may predict lung function decline and exacerbations in COPD patients. Methods We retrospectively examined stable COPD patients with a minimum follow-up of 3 years at our outpatients' clinic. We collected information about lung volumes (FEV1, FVC), the total and differential WBC count, acute exacerbations of COPD (number in the 12 months before the beginning of the study=AE-COPD-B, and during the follow-up=AE-COPD-F), smoking status and treatment. FEV1 decline and AE-COPD-F were described by using a generalized linear model and a 2-level random intercept negative binomial regression, respectively. The models included eosinophil and neutrophil counts as potential predictors and were adjusted by sex, age, smoking status, AE-COPD-B, treatment with bronchodilators and inhaled corticosteroids (ICS). Results Sixty-eight patients were considered, 36 bEOS- (<170 cells/μL, the median value) and 32 bEOS+ (≥170 cells/μL). ∆FEV1 was higher in bEOS+ than bEOS- (34.86 mL/yr vs 4.49 mL/yr, p=0.029). After adjusting for potential confounders, the eosinophil count was positively (β=19.4; CI 95% 2.8, 36.1; p=0.022) and ICS negatively (β=-57.7; CI 95% -91.5,-23.9; p=0.001) associated with lung function decline. bEOS were not found to be associated with the number of AE-COPD-F. Conclusion In stable COPD patients, a higher level of blood eosinophils (albeit in the normal range) predicts a greater FEV1 decline, while ICS are associated with a slower progression of airflow obstruction.

Vegetable but not animal protein intake is associated to a better physical performance: a study on a general population sample of adults.

BACKGROUND: The research was conducted in the frame of a population-based, case control study, called Genes Environment Interaction in Respiratory Disease. OBJECTIVE: To assess the association between protein intake and physical performance in a general population sample. DESIGN: Researchers investigated the association between the participants' dietary information and their physical performance using the 6-min walking test and the distance walked in metres (6MWD) as main outcome measure. Information on dietary intake was collected using the validated European Investigation into Cancer and Nutrition food frequency questionnaires (FFQs). Then, daily intake of energy and macronutrients was estimated by means of the NAF software (nutritional analysis of FFQ). Linear regression models were used to evaluate the associations between vegetable, animal and total protein intakes and the 6MWD. The models were adjusted for socio-demographic features, total fats and available carbohydrate intakes. RESULTS: The participants were 223 subjects (57% females) aged between 23 and 68 years. Their mean vegetable and animal proteins intake for gram/kg of body weight/day were, respectively, 0.4 and 0.7. After adjusting for all the potential confounders, there was a significant increase of 20.0 (95% CI 0.8; 39.2) m in the distance walked for an increase in 10 g/day of vegetable proteins and non-significant variations of -1.8 (95% CI -9.3; 5.7) m for an increase in 10 g/day of animal proteins and of 0.5 (95% CI -6.8; 7.7) for an increase in 10 g/day of total proteins. DISCUSSION AND CONCLUSIONS: Our result suggests a positive role of vegetable proteins on physical performance. Whether this result is related to the high protein intake itself or may be a consequence of the other properties of plant-based foods deserves further investigation.

Dietary fats, olive oil and respiratory diseases in Italian adults: A population-based study.

BACKGROUND: Fat intake has been associated with respiratory diseases, with conflicting results. OBJECTIVE: We studied the association between asthma and rhinitis with dietary fats, and their food sources in an Italian population. METHODS: Clinical and nutritional information was collected for 871 subjects (aged 20-84) from the population-based multi-case-control study Genes Environment Interaction in Respiratory Diseases (GEIRD): 145 with current asthma (CA), 77 with past asthma (PA), 305 with rhinitis and 344 controls. Food intake was collected using the EPIC (European Investigation into Cancer and Nutrition) Food Frequency Questionnaire. The associations between fats and respiratory diseases were estimated by multinomial models. Fats and their dietary sources were analysed both as continuous variables and as quartiles. RESULTS: Monounsaturated fatty acids and oleic acid were associated with a reduced risk of CA in both continuous (RRR = 0.68, 95%CI: 0.48; 0.96; RRR = 0.69; 95%CI: 0.49; 0.97, per 10 g, respectively) and per-quartile analyses (p for trend = 0.028 and 0.024, respectively). Olive oil was associated with a decreased risk of CA (RRR = 0.80; 95%CI: 0.65; 0.98 per 10 g). An increased risk of rhinitis was associated with moderate total fat and SFA intake. CONCLUSIONS: High dietary intakes of oleic acid and of olive oil are associated with a lower risk of asthma but not of rhinitis.

In a randomized trial in prostate cancer patients, dietary protein restriction modifies markers of leptin and insulin signaling in plasma extracellular vesicles.

Obesity, metabolic syndrome, and hyperleptinemia are associated with aging and age-associated diseases including prostate cancer. One experimental approach to inhibit tumor growth is to reduce dietary protein intake and hence levels of circulating amino acids. Dietary protein restriction (PR) increases insulin sensitivity and suppresses prostate cancer cell tumor growth in animal models, providing a rationale for clinical trials. We sought to demonstrate that biomarkers derived from plasma extracellular vesicles (EVs) reflect systemic leptin and insulin signaling and respond to dietary interventions. We studied plasma samples from men with prostate cancer awaiting prostatectomy who participated in a randomized trial of one month of PR or control diet. We found increased levels of leptin receptor in the PR group in total plasma EVs and in a subpopulation of plasma EVs expressing the neuronal marker L1CAM. Protein restriction also shifted the phosphorylation status of the insulin receptor signal transducer protein IRS1 in L1CAM+ EVs in a manner suggestive of improved insulin sensitivity. Dietary PR modifies indicators of leptin and insulin signaling in circulating EVs. These findings are consistent with improved insulin and leptin sensitivity in response to PR and open a new window for following physiologic responses to dietary interventions in humans.

Restriction of dietary protein decreases mTORC1 in tumors and somatic tissues of a tumor-bearing mouse xenograft model.

Reduced dietary protein intake and intermittent fasting (IF) are both linked to healthy longevity in rodents, and are effective in inhibiting cancer growth. The molecular mechanisms underlying the beneficial effects of chronic protein restriction (PR) and IF are unclear, but may be mediated in part by a down-regulation of the IGF/mTOR pathway. In this study we compared the effects of PR and IF on tumor growth in a xenograft mouse model of breast cancer. We also investigated the effects of PR and IF on the mechanistic Target Of Rapamycin (mTOR) pathway, inhibition of which extends lifespan in model organisms including mice. The mTOR protein kinase is found in two distinct complexes, of which mTOR complex 1 (mTORC1) is responsive to acute treatment with amino acids in cell culture and in vivo. We found that both PR and IF inhibit tumor growth and mTORC1 phosphorylation in tumor xenografts. In somatic tissues, we found that PR, but not IF, selectively inhibits the activity of the amino acid sensitive mTORC1, while the activity of the second mTOR complex, mTORC2, was relatively unaffected by PR. In contrast, IF resulted in increased S6 phosphorylation in multiple metabolic tissues. Our work represents the first finding that PR may reduce mTORC1 activity in tumors and multiple somatic tissues, and suggest that PR may represent a highly translatable option for the treatment not only of cancer, but also other age-related diseases.