Marker Of Cellular Aging Research Articles

Risky family processes prospectively forecast shorter telomere length mediated through negative emotions.

This study was designed to examine prospective associations of risky family environments with subsequent levels of negative emotions and peripheral blood mononuclear cell telomere length (TL), a marker of cellular aging. A second purpose was to determine whether negative emotions mediate the hypothesized link between risky family processes and diminished telomere length. Participants were 293 adolescents (age 17 years at the first assessment) and their primary caregivers. Caregivers provided data on risky family processes when the youths were age 17 years, youths reported their negative emotions at age 18 years, and youths' TL was assayed from a blood sample at age 22 years. The results revealed that (a) risky family processes forecast heightened negative emotions (β = .316, p < .001) and diminished TL (β = -.199, p = .003) among youths, (b) higher levels of negative emotions forecast shorter TL (β = -.187, p = .012), and (c) negative emotions served as a mediator connecting risky family processes with diminished TL (indirect effect = -0.012, 95% CI [-0.036, -0.002]). These findings are consistent with the hypothesis that risky family processes presage premature cellular aging through effects on negative emotions, with potential implications for lifelong health. (PsycINFO Database Record

Metabolically healthy obese women have longer telomere length than obese women with metabolic syndrome.

IntroductionObesity is the principal component in the Metabolic Syndrome (MetS) that determines the progression of metabolic complications. Metabolically healthy obese (MHO) individuals seem to be protected against those complications. Telomere length (TL) as a novel marker of cellular aging had a complex relationship to the MetS. The principal aim of this study was to investigate the TL in MHO, and to study the association between TL and the worsening of the metabolic condition.Material and methodsWe have determined the absolute TL (aTL) in 400 women (mean age of 46.76 ± 15.47 years; range: 18–86 years), grouped according to the metabolic condition in three groups: metabolically healthy non-obese women (MHNO), MHO and obese women with MetS (MSO); and grouped according to the number of components of MetS.ResultsWe found that MHO displays significantly higher aTL than MSO (p = 0.033; r = -4.63; 95% CI r = -8.89 / -0.37), but did not differ from MHNO. A decrease in aTL with the progressive increase in the number of MetS components was also observed (p < 0.001; r = -2.06; 95% CI r = -3.13 / -0.99). In this way, our results indicate that aTL is influenced by the presence of MetS, but it is not affected by the presence of obesity.DiscussionWe found that shorter aTL is not associated with MHO, but is related to MetS and with the increased number of metabolic abnormalities.

Trait mindfulness at baseline predicts increases in telomerase activity over time

Introduction.Preliminary investigations of cross-sectional samples have linked trait mindfulness with measures related to the hypothalamic–pituitary–adrenal (HPA)-mediated stress response and to the inflammatory system, suggesting that this is one potential pathway linking mindfulness based interventions and health. However, no previous studies explored the association between the trait mindfulness construct and markers of cellular ageing.Methods.In the current study we examined in a sample of healthy mothers (n = 92) of a child with Autism Spectrum Disorder (i.e. women showing high levels of chronic psychological stress) the prospective associations between a multidimensional scale of trait mindfulness, the Five Facet Mindfulness Questionnaire (FFMQ), and telomerase activity (TA), a marker of cellular ageing and telomere homeostasis. Participants’ trait mindfulness and TA were assessed at baseline as well as 9 and 18 month follow-up.Results.Analysis showed that higher levels of baseline mindfulness on FFMQ observation and describe subscales were related to increase in TA from baseline to 9 month (r = 0.27, P = 0.03 and r = 0.24, P = .04, respectively). Additionally, the FFMQ Describe subscale was related to increase in TA from baseline to 18 month (r = .30, P = .02). Results are reported following covariate adjustment of age, BMI, ethnicity, and education.Discussion.Our results showed that higher levels of baseline mindfulness are associated with higher increases in TA after 9 months and 18 months, with increased TA reportedly being associated with decreased oxidative damage, increased telomere length and overall more functional cellular physiology. These findings support a role of mindfulness-related interventions to increase general and mental health.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Effect of yoga and meditation on accelerated cellular aging in major depressive disorder patients

IntroductionAccelerated aging is associated with major depressive disorder (MDD) and studies of yoga and meditation based lifestyle intervention (YMLI) on biomarkers of cellular aging are lacking.Aim and objectivesTo investigate the peripheral blood biomarkers of cellular aging in MDD patients after short term YMLI. Biomarkers include DNA damage, oxidative stress (OS), telomere attrition, and nutrition sensing assessed respectively by 8-hydroxy 2’- deoxyguanosine (8-OHdG); reactive oxygen species (ROS) and total antioxidant capacity (TAC); telomere length and telomerase activity; and sirtuin-1.MethodsWe consecutively enrolled 33 MDD patients and 40 healthy subjects; 30 MDD patients were followed up with 12- week YMLI. Biomarkers of cellular aging in peripheral blood were measured with assay kits. All patients were evaluated by examining the correlation between cellular aging markers and Montgomery–Asberg Depression Rating Scale (MADRS) scores.ResultsThe levels of DNA damage, OS, and telomere attrition in MDD patients were significantly higher than healthy subjects (all P = 0.005). The MADRS scores had a significantly positive association with 8-OHdG and ROS levels and negative association with TAC, telomerase and sirtuin-1 levels (all P &lt; 0.01).ConclusionsPeripheral blood biomarker levels in our results suggest significant cellular aging in MDD patients compared to healthy subjects. There was strong correlation between the changes in biomarkers of cellular aging and clinical improvement in MDD. Our study is the first to show significant increase in sirtuin-1 levels in MDD patients after yoga and meditation. Therefore, biomarkers of cellular aging might be indicators of MDD severity and clinical remission after YMLI.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Depression, telomeres and mitochondrial DNA: between- and within-person associations from a 10-year longitudinal study

Alterations in cellular aging, indexed by leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn), might partly account for the increased health risks in persons with depression. Although some studies indeed found cross-sectional associations of depression with LTL and mtDNAcn, the longitudinal associations remain unclear. This 10-year longitudinal study examined between- and within-person associations of depressive symptoms with LTL and mtDNAcn in a large community sample. Data are from years 15, 20 and 25 follow-up evaluations in 977 subjects from the Coronary Artery Risk Development in Young Adults study. Depressive symptoms (years 15, 20, 25) were assessed with the Center for Epidemiologic Studies Depression (CES-D) scale; LTL (years 15, 20, 25) and mtDNAcn (years 15, 25) were measured in whole blood by quantitative PCR. With mixed-model analyses, we explored between- and within-person associations between CES-D scores and cellular aging markers. Results showed that high levels of depressive symptomatology throughout the 10-year time span was associated with shorter average LTL over 10 years (B=-4.2; P=0.014) after covarying for age, sex, race and education. However, no within-person association was found between depressive symptoms and LTL at each year (B=-0.8; P=0.548). Further, we found no between-person (B=-0.2; P=0.744) or within-person (B=0.4; P=0.497) associations between depressive symptomatology and mtDNAcn. Our results provide evidence for a long-term, between-person relationship of depressive symptoms with LTL, rather than a dynamic and direct within-person relationship. In this study, we found no evidence for an association between depressive symptoms and mtDNAcn.

Early life infection, but not breastfeeding, predicts adult blood telomere lengths in the Philippines.

Telomeres are repetitive DNA at chromosomes ends that shorten with age due to cellular replication and oxidative stress. As telomeres shorten, this can eventually place limits on cell replication and contribute to senescence. Infections are common during early development and activate cellular immune responses that involve clonal expansion and oxidative stress. As such, a high infectious disease burden might shorten blood telomere length (BTL) and accelerate the pace of immune senescence. To test this, BTL measured in young adults (21.7 ± 0.3 years old) from the Philippines (N = 1,759) were linked to prospectively collected early life data on infectious burden. As predicted, increased early life diarrheal prevalence was associated with shorter adult BTL. The association was most marked for infections experienced from 6 to 12 months, which corresponds with weaning and maximal diarrheal burden. A standard deviation increase in infections at 6-12 m predicts a 45 bp decrease in BTL, equivalent to 3.3 years of adult telomeric aging in this population. Contrary to expectations, breastfeeding duration was not associated with BTL, nor did effects vary by sex. These findings show that infancy diarrheal disease predicts a marker of cellular aging in adult immune cells. These findings suggest that early life infectious burden may influence late life health, or alternatively, that short TL in early life increases infectious disease susceptibility.

The age‐dependent association between aortic pulse wave velocity and telomere length

Key points Age significantly modifies the relationship between aortic pulse wave velocity and telomere length.The differential relationships observed between aortic pulse wave velocity and telomere length in younger and older individuals suggest that the links between cellular and vascular ageing reflect a complex interaction between genetic and environmental factors acting over the life‐course. Ageing is associated with marked large artery stiffening. Telomere shortening, a marker of cellular ageing, is linked with arterial stiffening. However, the results of existing studies are inconsistent, possibly because of the confounding influence of variable exposure to cardiovascular risk factors. Therefore, we investigated the relationship between telomere length (TL) and aortic stiffness in well‐characterized, younger and older healthy adults, who were pre‐selected on the basis of having either low or high aortic pulse wave velocity (aPWV), a robust measure of aortic stiffness. Demographic, haemodynamic and biochemical data were drawn from participants in the Anglo‐Cardiff Collaborative Trial. Two age groups with an equal sex ratio were examined: those aged <30 years (younger) or >50 years (older). Separately for each age group and sex, DNA samples representing the highest (n = 125) and lowest (n = 125) extremes of aPWV (adjusted for blood pressure) were selected for analysis of leukocyte TL. Ultimately, this yielded complete phenotypic data on 904 individuals. In younger subjects, TL was significantly shorter in those with high aPWV vs. those with low aPWV (P = 0.017). By contrast, in older subjects, TL was significantly longer in those with high aPWV (P = 0.001). Age significantly modified the relationship between aPWV and TL (P < 0.001). Differential relationships are observed between aPWV and TL, with an inverse association in younger individuals and a positive association in older individuals. The links between cellular and vascular ageing reflect a complex interaction between genetic and environmental factors acting over the life‐course.

Red Wine Prevents the Acute Negative Vascular Effects of Smoking

BackgroundModerate consumption of red wine is associated with fewer cardiovascular events. We investigated whether red wine consumption counteracts the adverse vascular effects of cigarette smoking. MethodsParticipants smoked 3 cigarettes alone or after drinking a titrated volume of red wine. Clinical chemistry, blood counts, plasma cytokine enzyme-linked immunosorbent assays, immunomagnetic separation of CD14+ monocytes for gene expression analysis, fluorescence-activated cell sorting for microparticles, and isolation of circulating mononuclear cells to measure telomerase activity were performed, and urine cotinine levels were quantified. ResultsCompared with baseline, leukocytosis (P = .019), neutrophilia (P <.001), lymphopenia (P <.001), and eosinopenia (P = .008) were observed after only smoking. Endothelial and platelet-, monocyte-, and leukocyte-derived microparticles (P <.001 each) were elevated. In monocytes, messenger RNA expression of interleukin (IL)-6 (2.6- ± 0.57-fold), tumor necrosis factor alpha (2.2- ± 0.62-fold), and IL-1b (2.3- ± 0.44-fold) were upregulated, as was IL-6 (1.2 ± 0.12-fold) protein concentration in plasma. Smoking acutely inhibited mononuclear cell telomerase activity. Markers of endothelial damage, inflammation, and cellular aging were completely attenuated by red wine consumption. ConclusionCigarette smoke results in acute endothelial damage, vascular and systemic inflammation, and indicators of the cellular aging processes in otherwise healthy nonsmokers. Pretreatment with red wine was preventive. The findings underscore the magnitude of acute damage exerted by cigarette smoking in “occasional lifestyle smokers” and demonstrate the potential of red wine as a protective strategy to avert markers of vascular injury.

Childhood Personality, Betrayal Trauma, and Leukocyte Telomere Length in Adulthood: A Lifespan Perspective on Conscientiousness and Betrayal Traumas as Predictors of a Biomarker of Cellular Aging.

Conscientiousness is associated with longevity. As such, identifying the biological pathways linking personality to mortality is important. This study employs longitudinal data spanning >40 years to test prospective associations with Leukocyte Telomere Length (LTL), a potential marker of cellular aging. Because telomeres shorten over time, and are sensitive to oxidative stress, shorter LTL may reflect cumulative damage associated with negative health behaviors and past stressful events. We investigated childhood conscientiousness as a protective factor, expecting an association with longer LTL in adulthood, possibly reflecting slower LTL shortening. Potential lifespan pathways involving childhood trauma, smoking behaviors, and Body Mass Index (BMI) were explored. Childhood conscientiousness showed a small raw association with LTL (r = .08, p = .04), although this effect did not persist when controlling for age and sex. Despite this lack of a direct effect on LTL, we detected an indirect effect operating jointly through BMI and smoking. Higher rates of childhood betrayal trauma were associated with shorter LTL. Contrary to our hypothesis that conscientiousness would buffer this effect, we found evidence for an interaction with childhood betrayal traumas where the association between childhood betrayal traumas and LTL was larger for those higher on conscientiousness in childhood.

Early exclusive breastfeeding is associated with longer telomeres in Latino preschool children

Telomere length (TL) is a marker of cellular aging, with the majority of lifetime attrition occurring during the first 4 y. Little is known about risk factors for telomere shortening in childhood. We evaluated the relation between early life feeding variables and preschool TL. We assessed the relation between dietary, feeding, and weight-associated risk factors measured from birth and TL from blood samples taken at 4 y of age (n = 108) and 5 y of age (n = 92) in a cohort of urban, Latino children (n = 121 individual children). Feeding variables were evaluated in children with repeat measurements (n = 77). Mean TL (in bp) was associated with exclusive breastfeeding at 4-6 wk of age (adjusted coefficient: 353.85; 95% CI: 72.81, 634.89; P = 0.01), maternal TL (adjusted coefficient: 0.32; 95% CI: 0.11, 0.54; P < 0.01), and older paternal age (adjusted coefficient: 33.27; 95% CI: 4.10, 62.44; P = 0.03). The introduction of other foods or drinks in addition to breast-milk or replacement-milk substitutes before 4-6 wk of age was associated with mean TL at 4 and 5 y of age (adjusted coefficient: -457.01; 95% CI: -720.50, -193.51; P < 0.01). Infant obesity at 6 mo of age and soda consumption at 4 y of age mediated the relation in part between exclusive breastfeeding at 4-6 wk of age and mean TL at 4 and 5 y of age. High soda consumption at 3 y of age was associated with an accelerated attrition from 4 to 5 y of age (adjusted coefficient: -515.14; 95% CI: -986.06, -41.22; P = 0.03). Exclusive breastfeeding at 4-6 wk of age may have long-term effects on child health as evidenced by longer TL at 4 and 5 y of age.

One-carbon metabolites and telomere length in a prospective and randomized study of B- and/or D-vitamin supplementation.

Vitamin B deficiency is common in elderly people and has been associated with an increased risk of developing age-related diseases. B-vitamins are essential for the synthesis and stability of DNA. Telomers are the end caps of chromosomes that shorten progressively with age, and short telomers are associated with DNA instability. In the present randomized intervention study, we investigated whether the one-carbon metabolism is related to telomere length, a surrogate marker for cellular aging. Sixty-five subjects (>54years) were randomly assigned to receive either a daily combination of vitamin D3 (1200IU), folic acid (0.5mg), vitamin B12 (0.5mg), vitamin B6 (50mg) and calcium carbonate (456mg) (group A) or vitamin D3 and calcium carbonate alone (group B). Blood testing was performed at baseline and after 1year of supplementation. The concentrations of several metabolites of the one-carbon pathway, as well as relative telomere length (RTL) and 5,10-methylenetetrahydrofolate reductase C677T genotype, were analyzed. At baseline, age- and gender-adjusted RTL correlated with total folate and 5-methyltetrahydrofolate (5-methylTHF). Subjects with RTL above the median had higher concentrations of total folate and 5-methylTHF compared to subjects below the median. At study end, gender- and age-adjusted RTL correlated in group A with methylmalonic acid (MMA; r=-0.460, p=0.0012) and choline (r=0.434, p=0.0021) and in group B with 5,10-methenyltetrahydrofolate (r=0.455, p=0.026) and dimethylglycine (DMG; r=-0.386, p=0.047). Subjects in the group A with RTL above the median had lower MMA and higher choline compared to subjects below the median. The present pilot study suggests a functional relationship between one-carbon metabolism and telomere length. This conclusion is supported by several correlations that were modified by B-vitamin supplementation. In agreement with our hypothesis, the availability of nucleotides and methylation groups seems to impact telomere length. Due to the small sample size and the limitations of the study, further studies should confirm the present results in a larger cohort.

RELATION OF CARDIOVASCULAR RISK FACTORS AND LEUKOCYTE TELOMERE LENGTH

Telomere length (TL) is a recognized marker of replicative cellular ageing, and related to the ageing of cardiovascular system with the risk of cardiovascular diseases development (CVD). Chronic inflammation and oxidative stress significantly determine the velocity of telomeres shortening, and most of CVD risk factors (RF) closely related to these proceses; and it is possible to suggest that relationship of TL and RF determine CVD risk. However, clinical studies on this processes elaboration are lacking. Aim. To study relation of TL with traditional and some “new” RF in persons of different age without clinical signs of CVD, related to atherosclerosis. Material and methods. Totally, 303 patients included, of the age 25-91 y.o., without signs of CVD and other chronic diseases, not taking regularly and medications. All patients underwent traditional and some “novel” RF. TL was measured via real time polymerase chain reaction. Results. According to the regression model, TL is independently related to age, C-reactive protein (marker of inflammation), urea (oxidative stress maker), and metabolic status markers as waist circumference, insulin resistance index HOMA, fasting glucose level; the most significant predictor is HOMA (p=0,0001). Risk of having shortened telomeres increases 12 times with increased urea, 2,4 times with insulin resistance, 2 times in fasting hyperglycemia. Conclusion. Revealing of the factors that are related to cellular ageing makes it to define the most potentially benefit targets for interventions towards early and effective CVD prevention.

Income and Markers of Immunological Cellular Aging.

Socioeconomic disadvantage may contribute to poor health through immune-related biological mechanisms. We examined the associations between socioeconomic status, as measured by annual household income, and T-cell markers of aging, including the ratios of CD4 and CD8 effector cells to naïve cells (E/N ratio) and the CD4/CD8 T-cell ratio. We hypothesized that participants with a lower income would have higher E/N ratios and lower CD4/CD8 ratios compared with participants with a higher income, and that these associations would be partially mediated by elevated cytomegalovirus (CMV) IgG antibody levels, a virus implicated in aging and clonal expansion of T cells. Data were from 79 individuals who participated in the population-based Detroit Neighborhood Health Study. We used linear regression to quantify the association between a $10,000 decrease in income and each ratio outcome. After adjustment for age, sex, race, smoking, medication use, and lifetime history of mental health conditions, lower income was associated with a 0.41 (95% confidence interval = 0.09-0.72) log-unit increase in the CD4 E/N ratio and a 0.20 (95% confidence interval = 0.02-0.39) log-unit increase in the CD8 E/N ratio. CMV immunoglobulin G antibody level partially mediated these associations. Our study suggests that low socioeconomic status is associated with immunological aging as measured by the E/N ratio and that impaired immune control of CMV may partially mediate these associations.

VprBP, an HIV target protein, is vital for immune responses by controlling T cell growth, proliferation and senescence.

Abstract Naïve mature T cells are maintained in a quiescent state with a low rate of cell size growth (biomass increase due to enhanced metabolism and biosynthesis) and proliferation. Disturbances inflicted by infection and inflammation, often trigger cells to exit quiescence and enter cell cycle, followed by rapid proliferation to restore homeostasis. Cell size growth is imperative for proliferating cells to compensate for the halving of cellular constituents for each division. Thus, proper coordination of cell growth and cell cycle entry of T cells is essential to mount effective immune response. Nonetheless, little is known about how cell cycle entry is controlled and even less about how cell size growth is regulated in T cells. We studied protein expression during T cell growth and cell cycle entry using quantitative proteomic approach. VprBP, an HIV target protein, was identified to be one of the highly upregulated factors. We found that VprBP was required for the cell growth and cell cycle entry of activated T cells. VprBP deletion abrogated T cell expansion during antiviral and autoimmune responses in vivo. VprBP-deficient cells drastically stabilized p53 protein with elevated expression of p53 target genes. Intriguingly, we found that although p53 deletion failed to correct the T cell growth defect due to VprBP deletion, it largely restored the cell cycle entry of VprBP-deficient T cells. In addition, VprBP deletion led to a premature senescence phenotype in T cells associating with increased cellular aging markers. These results suggest that VprBP controls T cell growth, cell cycle entry and senescence via discrete molecular programs. The recent findings and the underlying mechanisms will be discussed in detail in this presentation.

Telomere length, antioxidant status and incidence of ischaemic heart disease in type 2 diabetes

BackgroundType 2 diabetes (T2D) is associated with an increased risk of ischaemic heart disease (IHD). An accelerated process of vascular ageing induced by an increased oxidative stress exposure is suggested as potential pathway accounting for this association. However, no studies have explored the relationship between markers of vascular ageing, measures of oxidative stress and risk of IHD in T2D. ObjectivesTo explore the association between plasma antioxidant status, marker of cellular ageing (leukocyte telomere length, LTL) and 10years risk of IHD in patients with T2D. MethodsBetween 2001 and 2002, 489 Caucasians subjects with T2D were enrolled at the diabetic clinic, University College London Hospital. Plasma total anti-oxidant status (TAOS) and LTL were measured by photometric microassay and RT-PCR, respectively. The incidence of IHD over 10years was determined through linkage with the national clinical audit of acute coronary syndrome in UK. ResultsAt baseline, TAOS was associated with LTL (age adjusted: r=0.106, p=0.024). After 10years, 61 patients developed IHD. Lower TAOS and shorter LTL at baseline predicted an increased IHD risk at follow-up (age adjusted: p=0.033 and p=0.040, respectively). These associations were independent of age, gender, cardiovascular risk factors, circulating levels of CRP and medication differences. ConclusionsReduced TAOS and short LTL are interrelated pathways which predict risk of IHD in patients with T2D. Our findings suggest that antioxidant defences are important to maintain telomere integrity, potentially reducing the progression of vascular ageing in patients with T2D.

Number of Children and Telomere Length in Women: A Prospective, Longitudinal Evaluation.

Life history theory (LHT) predicts a trade-off between reproductive effort and the pace of biological aging. Energy invested in reproduction is not available for tissue maintenance, thus having more offspring is expected to lead to accelerated senescence. Studies conducted in a variety of non-human species are consistent with this LHT prediction. Here we investigate the relationship between the number of surviving children born to a woman and telomere length (TL, a marker of cellular aging) over 13 years in a group of 75 Kaqchikel Mayan women. Contrary to LHT’s prediction, women who had fewer children exhibited shorter TLs than those who had more children (p = 0.045) after controlling for TL at the onset of the 13-year study period. An “ultimate” explanation for this apparently protective effect of having more children may lay with human’s cooperative-breeding strategy. In a number of socio-economic and cultural contexts, having more chilren appears to be linked to an increase in social support for mothers (e.g., allomaternal care). Higher social support, has been argued to reduce the costs of further reproduction. Lower reproductive costs may make more metabolic energy available for tissue maintenance, resulting in a slower pace of cellular aging. At a “proximate” level, mechanisms involved may include the actions of the gonadal steroid estradiol, which increases dramatically during pregnancy. Estradiol is known to protect TL from the effects of oxidative stress as well as increase telomerase activity, an enzyme that maintains TL. Future research should explore the potential role of social support as well as that of estradiol and other potential biological pathways in the trade-offs between reproductive effort and the pace of cellular aging within and among human as well as in non-human populations.

Análisis de la longitud de los telómeros en obesos metabólicamente sanos

Obesity is the principal component in Metabolic Syndrome (MetS) and determines the progression of metabolic complications. Metabolically healthy obese individuals (MHO) seem to be protected against those complications. Telomere length (TL), as a novel marker of cellular aging, has a complex relationship with MetS. The principal aim of this study was to investigate TL in MHO, and to study the association between TL and the number of MetS components.A study was conducted on 398 women (mean age: 46.76±15.47 years; range: 18 - 86 years), grouped according to the number of MetS components (0, 1+2, MetS), a group of normal-weight individuals with 0 MetS components (NW0), and a group of obese without MetS (MHO).No differences were found in the TL of the MHO group compared to the NW0, but it was significantly higher than that of individuals with MetS (P=.032). A decrease in TL was observed with a progressive increase in the number of MetS components (P=.004), whereas the group of individuals without MetS components had significantly longer TL than the groups with 1 and 2 components (P=.027), and MetS (P=.003).Shorter TL is not associated with MHO, but is related to MetS and with an increased number of metabolic abnormalities.

Income and Markers of Immunological Cellular Aging

Income and Markers of Immunological Cellular Aging

Poor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male rats.

ABSTRACT‘Developmental programming’, which occurs as a consequence of suboptimal in utero and early environments, can be associated with metabolic dysfunction in later life, including an increased incidence of cardiovascular disease and type 2 diabetes, and predisposition of older men to sarcopenia. However, the molecular mechanisms underpinning these associations are poorly understood. Many conditions associated with developmental programming are also known to be associated with the aging process. We therefore utilized our well-established rat model of low birth weight and accelerated postnatal catch-up growth (termed ‘recuperated’) in this study to establish the effects of suboptimal maternal nutrition on age-associated factors in skeletal muscle. We demonstrated accelerated telomere shortening (a robust marker of cellular aging) as evidenced by a reduced frequency of long telomeres (48.5-8.6 kb) and an increased frequency of short telomeres (4.2-1.3 kb) in vastus lateralis muscle from aged recuperated offspring compared to controls. This was associated with increased protein expression of the DNA-damage-repair marker 8-oxoguanine-glycosylase (OGG1) in recuperated offspring. Recuperated animals also demonstrated an oxidative stress phenotype, with decreased citrate synthase activity, increased electron-transport-complex activities of complex I, complex II-III and complex IV (all markers of functional mitochondria), and increased xanthine oxidase (XO), p67phox and nuclear-factor kappa-light-chain-enhancer of activated B-cells (NF-κB). Recuperated offspring also demonstrated increased antioxidant defense capacity, with increased protein expression of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase and heme oxygenase-1 (HO1), all of which are known targets of NF-κB and can be upregulated as a consequence of oxidative stress. Recuperated offspring also had a pro-inflammatory phenotype, as evidenced by increased tumor necrosis factor-α (TNFα) and interleukin-1β (IL1β) protein levels. Taken together, we demonstrate, for the first time to our knowledge, an accelerated aging phenotype in skeletal muscle in the context of developmental programming. These findings may pave the way for suitable interventions in at-risk populations.

Genetics: Dynamic Cellular Aging Markers Associated with Major Depression

Psychiatric diseases are associated with an increased rate of somatic age-related illness. A new study sheds light on putative mediating cellular mechanisms by linking increased mitochondrial DNA copy number and decreased telomere length to childhood stress and major depression.