Limited TTP supply affects telomere length regulation in a telomerase-independent fashion

An adequate supply of nucleotides is essential for DNA replication and DNA repair. Moreover, inhibition of TTP synthesis can cause cell death by a poorly characterized mechanism called thymine-less death. In the yeast Saccharomyces cerevisiae, the genes encoding thymidylate synthetase (CDC21) and thymidylate kinase (CDC8) are both essential for de novo TTP synthesis. The effects of temperature-sensitive mutations in these genes have been characterized and, curiously, the phenotypes displayed by cells harboring them include shortened telomeric repeat tracts. This finding raised the possibility that the enzyme telomerase is very sensitive to TTP-pools. We tested this possibility in vivo by assessing telomerase-dependent extension in situations of lowered TTP supply. The results show that the above-mentioned short telomere phenotype is not a consequence of an inability of telomerase to elongate telomeres when TTP synthesis is impaired. Moreover, this telomere shortening was abolished in cells harboring a mutation in DNA polymerase α. Previously, this same mutation was shown to affect the coordination between conventional replication and telomerase-mediated extension. These results thus re-emphasize the importance of the interplay between conventional replication and telomerase-mediated addition of telomeric repeats in telomere replication

Effect of Resistance Training on Hematological Blood Markers in Older Men and Women: A Pilot Study

The aim of this study was to examine the effects of resistance training on hematological blood markers in older individuals. Twenty-nine men and women participated to this study. Subjects were randomized in 2 groups: (1) control (n = 13) and (2) resistance training (n = 16). At baseline and after the intervention, subjects were submitted to a blood sample to determine their hematological profile (red blood cells, hemoglobin, hematocrit, platelets, leukocytes, neutrophils, lymphocytes, monocytes, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red cell distribution width). At baseline, no difference was observed between groups. Moreover, we found no significant difference after the intervention on any of these markers. A 6-month resistance program in healthy older individuals seems to have no beneficial nor deleterious effects on hematological blood parameters. However, resistance training was well tolerated and should be recommended for other health purposes. Further studies are needed to confirm these results in a large population

Association between Abdominal Fat (DXA) and Its Subcomponents (CT Scan) before and after Weight Loss in Obese Postmenopausal Women: A MONET Study

Introduction. Subcutaneous fat (ScF) and visceral fat (VF) measurements using CT scan are expensive and may imply significant radiation doses. Cross-sectional studies using CT scan showed that ScF and VF are significantly correlated with abdominal fat measured by DXA (AF-DXA). The association has not been studied after a weight loss. Objective. To determine (1) the associations between AF-DXA and ScF and VF before and after weight loss and (2) the associations between their changes. Methods. 137 overweight/obese postmenopausal women were divided in two groups (1-caloric restriction or 2-caloric restriction + resistance training). AF was assessed using DXA and CT scan. Results. Correlations between AF-DXA and ScF (before: r = 0.87, after; r = 0.87; P < .01) and, AF-DXA and VF (before: r = 0.61, after; r = 0.69; P < .01) are not different before and after the weight loss. Correlations between delta AF-DXA and delta ScF (r = 0.72; P < .01) or delta VF (r = 0.51; P < .01) were found. Conclusion. The use of AF-DXA as a surrogate for VF after weight loss is questionable, but may be interesting for ScF

Contribution of abdominal adiposity to age-related differences in insulin sensitivity and plasma lipids in healthy nonobese women

WSTĘP. Autorzy sprawdzili słuszność hipotezy zakładającej, że związany z wiekiem przyrost tkanki tłuszczowej trzewnej odpowiada częściowo za ujemny wpływ na insulinowrażliwość i profil lipidowy u kobiet bez otyłości. MATERIAŁ I METODY. Bezpośrednio oceniono: powierzchnię podskórnej i trzewnej tkanki tłuszczowej (tomografia komputerowa), zużycie glukozy (badanie metodą hiperinsulinowej/euglikemicznej klamry metabolicznej), elementy składowe organizmu (metoda absorpcjometrii promieniami X dwoistej energii), profil lipidowy oraz maksymalne zużycie tlenu (VO2max) u 178 kobiet bez otyłości, zakwalifikowanych do odpowiednich grup wiekowych: grupa 1 - 28 &plusmn; 4 lata (n = 88); grupa 2 - 46 &plusmn; 2 lata (n = 38); grupa 3 - 53 &plusmn; 2 lata (n = 31); grupa 4 - 67 &plusmn; 6 lat (n = 21). WYNIKI. Powierzchnia trzewnej tkanki tłuszczowej zwiększa się wraz z wiekiem (2,36 cm2 rocznie, p < 0,0001). Zanotowano związany z wiekiem wzrost stężenia cholesterolu całkowitego (p < 0,0003), triglicerydów (p < 0,0009), cholesterolu frakcji LDL (p < 0,027) i stosunku stężenia cholesterolu całkowitego do cholesterolu frakcji HDL (p < 0,042). Obserwowane różnice w insulinowrażliwości także wiązały się z wiekiem, jednakże w tym przypadku zależność była odmienna. Insulinowrażliwość, wyrażona jako całkowita lub przeliczona na kilogram beztłuszczowej masy ciała, była najniższa w grupie 4, ale nie różniła się istotnie między grupami 1, 2 i 3. Po analizie statystycznej, uwzględniającej powierzchnię tkanki tłuszczowej trzewnej, niższa insulinowrażliwość utrzymywała się, jednocześnie, relatywnie zmniejszyła się różnica w porównaniu z pozostałymi grupami. Wpływ zawartości trzewnej tkanki tłuszczowej na związane z wiekiem zmiany profilu lipidowego był silniejszy. Różnice w powierzchni trzewnej i głębokiej podskórnej tkanki tłuszczowej znosiły wpływ wieku na stężenie cholesterolu całkowitego, triglicerydów i cholesterolu frakcji LDL. Nie obserwowano natomiast wpływu wartości VO2max lub aktywnego wypoczynku na zależne od wieku zmiany w insulinowrażliwości bądź profilu lipidowym. WNIOSKI. 1) Wraz z wiekiem zwiększa się powierzchnia trzewnej tkanki tłuszczowej, podczas gdy zmniejszenie insulinowrażliwości obserwuje się tylko u kobiet starszych; 2) Związane z wiekiem różnice w trzewnej tkance tłuszczowej tylko w niewielkim stopniu odpowiadają za spadek insulinowrażliwości u kobiet bez otyłości; 3) Niepożądane zmiany profilu lipidowego w dużym stopniu wiążą się z zależnym od wieku przyrostem trzewnej tkanki tłuszczowej.INTRODUCTION. We examined the hypothesis that an age-related increase in the compartments of visceral fat would account, in part, for the deleterious changes in insulin sensitivity and blood lipid profile in nonobese women. MATERIAL AND METHODS. We directly assessed visceral and subcutaneous abdominal adipose tissue areas (computed tomography), glucose disposal (hyperinsulinemic-euglycemic clamp), body composition (dual energy X-ray absorptiometry), blood-lipid profile, and aerobic fitness (VO2max) in 178 nonobese women categorized into four age groups: group 1, 28 &plusmn; 4 years, n = 88; group 2, 46 &plusmn; 2 years, n = 38; group 3, 53 &plusmn; 2 years, n = 31; and group 4, 67 &plusmn; 6 years, n = 21. RESULTS. Visceral abdominal adipose tissue area increased with age (2.36 cm2 per year, P < 0.0001). We noted an age-related increase in total cholesterol (P < 0.0003), triglycerides (P < 0.0009), LDL cholesterol (P < 0.027), and the ratio of total cholesterol to HDL cholesterol (P < 0.042). However, agerelated changes in insulin sensitivity exhibited a different age-related pattern. That is, insulin sensitivity, expressed on an absolute basis or indexed per kilogram of fat-free mass, was lowest in group 4 but was not significantly different among groups 1, 2, and 3. After statistical control for visceral fat, lower insulin sensitivity persisted in group 4, although differences were diminished relative to other groups. However, the effect of visceral fat on agerelated changes in the blood-lipid profile was stronger. That is, differences in visceral and deep subcutaneous adipose tissue area abolished age-related differences in total cholesterol, triglycerides, and LDL cholesterol. No independent effects of VO2max or leisure-time physical activity on age-related changes in insulin sensitivity or on the blood-lipid profile were noted. CONCLUSIONS. We conclude that 1) visceral fat shows an increase with advancing age, whereas a decrease in insulin sensitivity was noted only in older women; 2) age-related differences in visceral fat explain only a modest part of the decline in insulin sensitivity in nonobese women; and 3) unfavorable changes in plasma lipids were strongly associated with the age-related increase in visceral abdominal adipose tissue

Association between Abdominal Fat (DXA) and Its Subcomponents (CT Scan) before and after Weight Loss in Obese Postmenopausal Women: A MONET Study

Introduction. Subcutaneous fat (ScF) and visceral fat (VF) measurements using CT scan are expensive and may imply significant radiation doses. Cross-sectional studies using CT scan showed that ScF and VF are significantly correlated with abdominal fat measured by DXA (AF-DXA). The association has not been studied after a weight loss. Objective. To determine (1) the associations between AF-DXA and ScF and VF before and after weight loss and (2) the associations between their changes. Methods. 137 overweight/obese postmenopausal women were divided in two groups (1-caloric restriction or 2-caloric restriction + resistance training). AF was assessed using DXA and CT scan. Results. Correlations between AF-DXA and ScF (before: r = 0.87, after; r = 0.87; P &lt; .01) and, AF-DXA and VF (before: r = 0.61, after; r = 0.69; P &lt; .01) are not different before and after the weight loss. Correlations between delta AF-DXA and delta ScF (r = 0.72; P &lt; .01) or delta VF (r = 0.51; P &lt; .01) were found. Conclusion. The use of AF-DXA as a surrogate for VF after weight loss is questionable, but may be interesting for ScF

SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition

BackgroundFollowing SARS-CoV-2 infection a significant proportion of convalescent individuals develop the post-COVID condition (PCC) that is characterized by wide spectrum of symptoms encompassing various organs. Even though the underlying pathophysiology of PCC is not known, detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be a consequence of aberrant immune response to the viral antigens. To test this hypothesis, we evaluated B cell and antibody responses to the SARS-CoV-2 antigens in PCC patients who experienced mild COVID-19 disease during the pre-vaccination period of COVID-19 pandemic.MethodsThe study subjects included unvaccinated male and female subjects who developed PCC or not (No-PCC) after clearing RT-PCR confirmed mild COVID-19 infection. SARS-CoV-2 D614G and omicron RBD specific B cell subsets in peripheral circulation were assessed by flow cytometry. IgG, IgG3 and IgA antibody titers toward RBD, spike and nucleocapsid antigens in the plasma were evaluated by ELISA.ResultsThe frequency of the B cells specific to D614G-RBD were comparable in convalescent groups with and without PCC in both males and females. Notably, in females with PCC, the anti-D614G RBD specific double negative (IgD-CD27-) B cells showed significant correlation with the number of symptoms at acute of infection. Anti-spike antibody responses were also higher at 3 months post-infection in females who developed PCC, but not in the male PCC group. On the other hand, the male PCC group also showed consistently high anti-RBD IgG responses compared to all other groups.ConclusionsThe antibody responses to the spike protein, but not the anti-RBD B cell responses diverge between convalescent males and females who develop PCC. Our findings also suggest that sex-related factors may also be involved in the development of PCC via modulating antibody responses to the SARS-CoV-2 antigens

Relationships between physical activity across lifetime and health outcomes in older adults: Results from the NuAge cohort

Abstract: Objectives: This study aims to (1) describe participation in four physical activity (PA) domains across life and (2) examine the influence of PA during adolescence, early, mid-life, and later adulthood on health variables at older age. Design: Retrospective, observational, population-based cohort. Setting: Longitudinal study Nutrition as a Determinant of Successful Aging study ParticipantS: 1 378 healthy older adults (667 men; 711 women; aged 67-84 yrs at baseline) Measurements: Using a modified version of the interviewer-administered Lifetime Total Physical Activity Questionnaire (LTPAQ) and life events calendar to facilitate the recall, participants reported the frequency, duration, and intensity of occupational (OPA), commuting (CPA), household (HPA), and leisure time (LTPA) they participated in at the ages of 15, 25, 45, and 65 years and at the first follow-up (aged 68-85 yrs at follow-up). Fat mass, lean body mass, body mass index, waist to hip ratio, fasting glucose, systolic and diastolic blood pressures, self-reported chronic diseases, and socio-demographic were assessed at baseline. Results: Changes in PA differed across sex and PA domain. However, there was a general decline in all PA domains among both sexes after the age of 65. In multiple regression analyses, current LTPA was systematically associated with more favorable waist to hip ratio and fat mass in both sexes, whereas CPA, OPA, and HPA across life were not consistently associated with health variables. Conclusion: PA domains during adolescence, early adulthood, and mid-life were not directly related to health variables at older age, while current LTPA was, suggesting it is never too late to start

Links Between Metabolic and Structural Changes in the Brain of Cognitively Normal Older Adults: A 4-Year Longitudinal Follow-Up

We aimed to longitudinally assess the relationship between changing brain energy metabolism (glucose and acetoacetate) and cognition during healthy aging. Participants aged 71 ± 5 year underwent cognitive evaluation and quantitative positron emission tomography (PET) and magnetic resonance imaging (MRI) scans at baseline (N = 25) and two (N = 25) and four (N = 16) years later. During the follow-up, the rate constant for brain extraction of glucose (Kglc) declined by 6%–12% mainly in the temporo-parietal lobes and cingulate gyri (p ≤ 0.05), whereas brain acetoacetate extraction (Kacac) and utilization remained unchanged in all brain regions (p ≥ 0.06). Over the 4 years, cognitive results remained within the normal age range but an age-related decline was observed in processing speed. Kglc in the caudate was directly related to performance on several cognitive tests (r = +0.41 to +0.43, allp ≤ 0.04). Peripheral insulin resistance assessed by the homeostasis model assessment of insulin resistance (HOMA-IR) was significantly inversely related to Kglc in the thalamus (r = −0.44, p = 0.04) and in the caudate (r = −0.43, p = 0.05), and also inversely related to executive function, attention and processing speed (r = −0.45 to −0.53, all p ≤ 0.03). We confirm in a longitudinal setting that the age-related decline in Kglc is directly associated with declining performance on some tests of cognition but does not significantly affect Kacac

SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition

Background Following SARS-CoV-2 infection a significant proportion of convalescent individuals develop the post-COVID condition (PCC) that is characterized by wide spectrum of symptoms encompassing various organs. Even though the underlying pathophysiology of PCC is not known, detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be a consequence of aberrant immune response to the viral antigens. To test this hypothesis, we evaluated B cell and antibody responses to the SARS-CoV-2 antigens in PCC patients who experienced mild COVID-19 disease during the pre-vaccination period of COVID-19 pandemic. Methods The study subjects included unvaccinated male and female subjects who developed PCC or not (No-PCC) after clearing RT-PCR confirmed mild COVID-19 infection. SARS-CoV-2 D614G and omicron RBD specific B cell subsets in peripheral circulation were assessed by flow cytometry. IgG, IgG3 and IgA antibody titers toward RBD, spike and nucleocapsid antigens in the plasma were evaluated by ELISA. Results The frequency of the B cells specific to D614G-RBD were comparable in convalescent groups with and without PCC in both males and females. Notably, in females with PCC, the anti-D614G RBD specific double negative (IgD-CD27-) B cells showed significant correlation with the number of symptoms at acute of infection. Anti-spike antibody responses were also higher at 3 months post-infection in females who developed PCC, but not in the male PCC group. On the other hand, the male PCC group also showed consistently high anti-RBD IgG responses compared to all other groups. Conclusions The antibody responses to the spike protein, but not the anti-RBD B cell responses diverge between convalescent males and females who develop PCC. Our findings also suggest that sex-related factors may also be involved in the development of PCC via modulating antibody responses to the SARS-CoV-2 antigens

Effects of β-hydroxy-β-methylbutyrate on aerobic-performance components and body composition in college students

The aim of this study was to determine the effects of oral ß-hydroxy-ß-methylbutyrate (HMB) supplementation (3 g/d) on selected components of aerobic performance and body composition of active college students. Subjects were randomly assigned to either an HMB (n = 8) or a placebo (PLA) group (n = 8) for a 5-wk supplementation period during which they underwent interval training 3 times a week on a treadmill. Aerobic-performance components were measured using a respiratory-gas analyzer. Body composition was determined using dual-energy X-ray absorptiometry. After the intervention, there were significant differences (P < 0.05) between the 2 groups in gains in maximal oxygen consumption (+8.4% for PLA and +15.5% for HMB) and in respiratory-compensation point (+8.6% for PLA and +13.4% for HMB). Regarding body composition, there were no significant differences. The authors concluded that HMB supplementation positively affects selected components of aerobic performance in active college students