Plant Foods Intake and Risk of Premature Aging in Adult Survivors of Childhood Cancer in the St Jude Lifetime Cohort (SJLIFE).

PURPOSE: To identify dietary factors that are related to premature aging in adult survivors of childhood cancer, we examined the associations between plant food intakes and age-related deficit accumulation. METHODS: A total of 3,322 childhood cancer survivors (age 18-65 years, mean = 31, standard deviation = 8.4) in the St Jude Lifetime Cohort had total fruit, total vegetables and subgroups, whole grains, refined grains, nuts/seeds, and nutrients intake assessed using a food frequency questionnaire. Premature aging at baseline was assessed by the deficit accumulation index (DAI) and categorized as low, medium, and high risk. Multinomial logistic regressions (reference: low risk) adjusting for confounders estimated odds ratios (ORs) and 95% CIs. Multivariable linear regression of a continuous intake against a continuous DAI was also performed. RESULTS: Dark green vegetable (ORhigh v low = 0.47 [95% CI, 0.28 to 0.78] per 1/2 cup/1,000 kcal increment) and nuts/seeds intakes (ORhigh v low = 0.71 [95% CI, 0.47 to 1.08] per 1 oz/1,000 kcal increment; coefficientlinear = -0.0115, P = .02) were associated with a lower risk of premature aging. Conversely, refined grain intake was related to an increased risk of premature aging (ORhigh v low = 1.33 [95% CI, 0.99 to 1.78], per 1 oz/1,000 kcal increment; coefficientlinear = 0.0093, P = .005). Fruit and whole grain intakes were not associated with premature aging risk. Among nutrients abundant in plant foods, dietary folate intake was associated with a lower risk of premature aging (ORhigh v low = 0.89 [95% CI, 0.80 to 0.99] per 50 mcg/1,000 kcal increase). Beta-carotene, lutein/zeaxanthin, and vitamin E intakes from foods were also related to a modestly lower, but not statistically significant, risk of premature aging. CONCLUSION: Specific plant foods are associated with lower risk of premature aging, providing targets for the interventions to promote healthy aging in childhood cancer survivors.

A matched cohort study investigating premature, accentuated, and accelerated aging in people living with HIV.

INTRODUCTION: The impact of HIV infection on the aging process is disputed and largely unknown. We aimed to identify whether people living with HIV experience premature, accelerated, and/or accentuated aging by investigating the development of four age-related non-communicable diseases in people living with versus without HIV. METHODS: This population-based matched cohort study design used UK-based primary care electronic health records from the IQVIA Medical Research Database. Between January 2000 and January 2020, all people living with and without HIV aged ≥18 years were eligible. Outcomes included cardiovascular disease (CVD), hypertension, type 2 diabetes mellitus (T2DM), and chronic kidney disease (CKD), which were identified by Read codes. We used age at diagnosis to investigate premature aging and age at exit date to investigate accentuation and acceleration. For each outcome, people with and without HIV were excluded if they had the outcome of interest at baseline. Participants were matched based on propensity scores (1:1 ratio). Linear regression was used to report any difference in age at diagnosis between the two groups and to report the prevalence trends for age at exit date. RESULTS: In total, 8880 people living with HIV were matched with 8880 people without HIV and were found to have an earlier onset of CVD (54.5 vs. 56.8; p = 0.002). Similarly, people living with HIV had an earlier onset of hypertension (49.7 vs. 51.4; p = 0.002). No difference was found for T2DM or CKD (53.4 vs. 52.6; p = 0.368 and 57.6 vs. 58.1; p = 0.483, respectively). The burden of CKD increased over time, whereas no difference in the burden was found for the other conditions. CONCLUSION: The earlier development of CVD and hypertension in people living with HIV than in those without HIV indicates premature aging, whereas the increased burden of CKD indicates accelerated aging.

DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function.

BACKGROUND: The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies. RESULTS: We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E-03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang's 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (ß = - 0.12, 95% CI = [- 0.16, - 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E-08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (ß = 0.12 [0.07, 0.16], p = 2.08E-06). The "first-generation" clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria. CONCLUSION: DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease.

Association of History of Psychopathology With Accelerated Aging at Midlife.

Importance: Individuals with mental disorders are at an elevated risk of developing chronic age-related physical diseases. However, it is not clear whether psychopathology is also associated with processes of accelerated aging that precede the onset of age-related disease. Objective: To test the hypothesis that a history of psychopathology is associated with indicators of accelerated aging at midlife. Design, Setting, and Participants: This prospective cohort study was based on the Dunedin Multidisciplinary Health and Development Study, a population-representative birth cohort of 1037 individuals born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand. Members were followed up to age 45 years (until April 2019). Data were analyzed from January 6 to December 7, 2020. Exposures: Mental disorders were assessed in 6 diagnostic assessments from ages 18 to 45 years and transformed through confirmatory factor analysis into continuous measures of general psychopathology (p-factor) and dimensions of internalizing, externalizing, and thought disorders (all standardized to a mean [SD] of 100 [15]). Main Outcomes and Measures: Signs of aging (biological pace of aging; declines in sensory, motor, and cognitive functioning; and facial age) were assessed up to age 45 years using previously validated measures including biomarkers, clinical tests, and self-reports. Results: Of the original 1037 cohort participants, 997 were still alive at age 45 years, of whom 938 (94%) were assessed (474 men [50.5%]). Participants who had experienced more psychopathology exhibited a faster pace of biological aging (ß, 0.27; 95% CI, 0.21-0.33; P < .01); experienced more difficulties with hearing (ß, 0.18; 95% CI, 0.12-0.24; P < .01), vision (ß, 0.08; 95% CI, 0.01-0.14; P < .05), balance (ß, 0.20; 95% CI, 0.14-0.26; P < .01), and motor functioning (ß, 0.19; 95% CI, 0.12-0.25; P < .01); experienced more cognitive difficulties (ß, 0.24; 95% CI, 0.18-0.31; P < .01); and were rated as looking older (ß, 0.20; 95% CI, 0.14-0.26; P < .01). Associations persisted after controlling for sex, childhood health indicators, maltreatment, and socioeconomic status and after taking into account being overweight, smoking, use of antipsychotic medication, and the presence of physical disease. Tests of diagnostic specificity revealed that associations were generalizable across externalizing, internalizing, and thought disorders. Conclusions and Relevance: In this cohort study, a history of psychopathology was associated with accelerated aging at midlife, years before the typical onset of age-related diseases. This link is not specific to any particular disorder family but generalizes across disorders. Prevention of psychopathology and monitoring of individuals with mental disorders for signs of accelerated aging may have the potential to reduce health inequalities and extend healthy lives.

Chronic Pain and Premature Aging - The Moderating Role of Physical Exercise.

Chronic pain induces a multitude of harmful effects; recently it has been suggested that chronic pain is also associated with premature aging, manifested in shortened telomere length (TL). However, evidence for this hypothesis is scarce and inconsistent. The aim was twofold: 1) Investigate whether chronic pain is associated with premature aging, and 2) Determine whether physical exercise (PE) moderates this association if it exists. Participants were 116 male subjects, with (n = 67) and without chronic pain (n = 49). Blood samples for TL analysis were collected and participants were interviewed and completed questionnaires. As a part of the cohort, we included people with physical disability; this variable was controlled in the analysis. The TL of individuals with chronic pain was significantly shorter than that of pain-free individuals. Regression analysis revealed a significant moderating effect of PE on chronic pain and TL, above and beyond the effects of disability, age, and weight. Whereas chronic pain was associated with shorter telomeres in participants who did not exercise, this association was nonsignificant among participants who did exercise. The results suggest that chronic pain is associated with premature ageing; however, PE may mitigate this association and may protect individuals against the harmful effects of chronic pain. PERSPECTIVE: The study suggests that it is important to monitor signs of premature ageing among chronic pain patients as they are at risk. However, chronic pain patients may benefit from regular PE in this respect as it may moderate premature ageing.

Association of Early-Life Adversity With Measures of Accelerated Biological Aging Among Children in China.

Importance: A growing body of literature suggests that exposure to early-life adversity (ELA) is associated with accelerated biological aging, offering 1 mechanism through which ELA may be associated with an increased risk for age-related disease. These investigations, however, have been predominantly cross-sectional and focused on adults and females. Objective: To evaluate associations of threat-related (ie, physical abuse) and deprivation-related (ie, emotional neglect) ELA exposure with cellular and reproductive strategy metrics of biological aging among boys and girls with specific genetic backgrounds around the period of pubertal onset. Design, Setting, and Participants: In this cohort study, 997 boys and girls in grade 1 to grade 3 from 3 large elementary schools were recruited from Bengbu, Anhui Province, China, and were followed up from March 21, 2016 (baseline; wave 1), for 4 consecutive years, through March 25, 2019. Main Outcomes and Measures: The outcome was accelerated biological aging in both cellular and reproductive strategy metrics: telomere attrition and age at thelarche (for girls) and testicular maturation (for boys). Multi-informant assessment of exposure to threat-related and deprivation-related ELA was done at baseline (wave 1) and 1-year follow-up (wave 2). The polygenic risk score (PRS) was computed based on 17 single-nucleotide variations for early pubertal timing. Results: Of the 997 participants (579 girls [58.1%]; mean [SD] age at baseline, 8.0 [0.8] years), 550 (55.2%) reported exposure to threat-related ELA and 443 (44.4%) reported exposure to deprivation-related ELA. Threat-related ELA was associated with onset of thelarche 2.6 months earlier and deprivation-related ELA with onset of thelarche 3.3 months earlier in exposed girls than in unexposed peers; these associations were observed only among girls with a low PRS. Among boys, a similar pattern was found. Threat-related ELA was associated with testicular volume of 4 mL or more 1.4 months earlier and deprivation-related ELA was associated with testicular volume of 4 mL or more 2.3 months earlier than in unexposed peers but only among those with a low PRS. Boys and girls with greater exposure to threats showed a significantly higher percentage of telomere length change during 1-year follow-up, but only among those with low PRS (boys: ß = 1.50; 95% CI, 0.80-2.21; P < .001; girls: ß = 2.40; 95% CI, 1.78-3.05; P < .001) and moderate PRS (boys: ß = 1.09; 95% CI, 0.43-1.75; P = .001; and girls: ß = 1.27; 95% CI, 0.77-1.77; P < .001). No associations of deprivation-related ELA with percentage of telomere length change were found. Conclusions and Relevance: This study suggests that the accelerating association of ELA with biological aging might occur at an earlier age and in a genetic background-dependent and dimension-specific manner.

Adult outcomes after preterm birth.

Extremely preterm birth reflects global disruption of the third trimester environment. Young adults born preterm have an adverse cardiovascular and metabolic health profile, together with molecular evidence of accelerated ageing and a reduced life expectancy. The underlying mechanism for these observations is unknown. This review summarises recent evidence of the lifetime effects of preterm birth and highlights the risks survivors face.

Subjective Cognitive Decline Among Sexual and Gender Minorities: Results from a U.S. Population-Based Sample.

The risk of dementia and mild cognitive impairment between older adults in same-sex relationships and those in opposite-sex relationships have been found to be statistically not different. However, studies examining subjective cognitive decline (SCD) among sexual and gender minority populations (SGM) are lacking. The primary objective was to determine if SGM report greater SCD compared to non-SGM populations in a U.S. population-based sample of non-institutionalized adults aged 45 and older. The secondary objective was to assess the association between gender and SCD. Cross-sectional data were obtained from the 2016 Behavioral Risk Factor Surveillance System (n = 36,734). There were 1,094 SGM adults in the sample. Descriptive statistics examined sociodemographic characteristics and their distribution by SCD and SGM status. Crude and multivariable logistic regression models were used to determine the association between SGM status, gender, and SCD. Adjusted models controlled for age, race/ethnicity, income, education, employment, marital status, depression, and diabetes. Statistically significant differences in SGM status and SCD existed by age, race/ethnicity, education, employment, marital status, and depression. Differences in SCD also existed by income and diabetes status. There was no statistically significant association between SGM status and SCD (OR: 0.88; 95% CI: 0.63-1.24). However, men had 64% higher odds (OR: 1.64; 95% CI: 1.44-1.88) of reporting SCD compared to women. Future studies examining the potential reasons for this null association, including resilience and/or premature aging are warranted. Future research assessing potential reasons for gender differences in SCD, whether physiological or environmental, is also needed.

Evidence for Accelerated Biological Aging in Young Adults with Prader-Willi Syndrome.

OBJECTIVE: Adults with Prader-Willi syndrome (PWS) are at increased risk of developing age-associated diseases early in life and, like in premature aging syndromes, aging might be accelerated. We investigated leukocyte telomere length (LTL), a marker of biological age, in young adults with PWS and compared LTL to healthy young adults of similar age. As all young adults with PWS were treated with growth hormone (GH), we also compared LTL in PWS subjects to GH-treated young adults born short for gestational age (SGA). DESIGN: Cross-sectional study in age-matched young adults; 47 with PWS, 135 healthy, and 75 born SGA. MEASUREMENTS: LTL measured by quantitative polymerase chain reaction, expressed as telomere/single copy gene ratio. RESULTS: Median (interquartile range) LTL was 2.6 (2.4-2.8) at a median (interquartile range) age of 19.2 (17.7-21.3) years in PWS, 3.1 (2.9-3.5) in healthy young adults and 3.1 (2.8-3.4) in the SGA group. Median LTL in PWS was significantly lower compared to both control groups (P < .01). In PWS, a lower LTL tended to be associated with a lower total IQ (r = 0.35, P = .08). There was no association between LTL and duration of GH treatment, cumulative GH dose, or several risk factors for type 2 diabetes mellitus or cardiovascular disease. CONCLUSIONS: Young adults with PWS have significantly shorter median LTL compared to age-matched healthy young adults and GH-treated young adults born SGA. The shorter telomeres might play a role in the premature aging in PWS, independent of GH. Longitudinal research is needed to determine the influence of LTL on aging in PWS.

Does education level protect us from rapid ageing? Sirtuin expression versus age and level of education.

PURPOSE: SIR proteins (silent information regulators, sirtuins, SIRT1 - SIRT7, SIR1 - SIR7) belong to NAD+-dependent deacetylases, enzymes taking part in a catalytic reaction of deacetylation, i.e. splitting the rest of acetic acid from protein substrates. Sirtuins play an important role in many cellular processes and are, therefore, involved in the ageing process and in the regulation of cell life. The aim of this paper is to verify the statistical hypothesis assuming the correlation between the age and level of education of examined persons and the expression of selected sirtuins (SIR1 - SIR7, SIRT1 - SIRT7) at the mRNA level in the Polish population. MATERIAL AND METHODS: 197 people, aged M = 38.27 (SD = 13.19), in whom expression at the level of mRNA for SIR1 - SIR7 was determined, took part in the study (99 healthy people with a negative history of mental and somatic diseases and 98 people with diagnosed recurrent depressive disorders). RESULTS: A significant correlation was found in the case of age of the examined individuals and the expression of SIR1 - SIR7 at the mRNA level (p < 0.001). Differences in the expression of SIR1 - SIR7 were also found in relation to the level of education (number of years of education) of the examined population (p < 0.001). CONCLUSIONS: 1. The higher the number of years of education, the higher the level of SIR1 and SIR6 expression, and the lower the level of SIR2, SIR3, SIR4, SIR5 and SIR7 expression. 2. With age, the level of SIR1 and SIR6 expression decreases and the expression of SIR2, SIR3, SIR4, SIR5 and SIR7 increases.

Risk factors for premature aging in childhood cancer survivors.

Over the last decades, the overall survival rate for childhood cancer has increased from 20% to 80%, which is the result of advances in treatment. Nevertheless, most data from the international registers of childhood cancer survivors (CCS) stress that this population of patients is at high risk for late sequelae and their biological aging starts earlier in life. Anticancer therapy (chemotherapy, radiotherapy, surgery, immunotherapy) affects the intracellular processes leading to the chronic deterioration of organ function and premature senescence. The present review focuses on the late effects of anticancer treatment on various human organs that may lead to premature aging.

Chronic Obstructive Pulmonary Disease as a Main Factor of Premature Aging.

(1) Background: Chronic obstructive pulmonary disease (COPD) is defined as an inflammatory disorder that presents an increasingly prevalent health problem. Accelerated aging has been examined as a pathologic mechanism of many chronic diseases like COPD. We examined whether COPD is combined with accelerated aging, studying two hormones, dehydroepiandrosterone (DHEA) and growth hormone (GH), known to be characteristic biological markers of aging. (2) Methods: Data were collected from 119 participants, 70 (58.8%) COPD patients and 49 (41.2%) from a health control group over the period of 2014⁻2016 in a spirometry program. Information about their medical history, tobacco use, and blood tests was obtained. (3) Results: The average age of the health control patients was 73.5 years (SD = 5.5), and that of the COPD patients was 75.4 years (SD = 6.9). Both groups were similar in age and sex. A greater proportion of smokers were found in the COPD group (87.1%) versus the control group (36.7%). The majority of COPD patients were classified as STAGE II (51.4%) and STAGE III (37.1%) according to GOLD (Global Initiative for Chronic Obstructive Pulmonary Disease). Levels of DHEA (SD = 17.1) and GH (SD = 0.37) were significantly lower in the COPD group (p < 0.001) compared to those in the controls (SD = 26.3, SD = 0.79). DHEA and GH were more significant and negatively correlated with age. The regression equation of DHEA with age produced a coefficient equal to 1.26. In this study, the difference in DHEA between COPD patients and controls was, on average, 30.2 µg/dL, indicating that the biological age of a COPD patient is on average about 24 years older than that of a control subject of the same age. Similarly, the difference in GH between COPD patients and controls was, on average, 0.42 ng/mL, indicating that the biological age of a COPD patient is on average about 13.1 years older than that of a control subject of the same age. (4) Conclusions: The findings of our study strongly suggest the presence of premature biological aging in COPD patients. Their biological age could actually vary from 13 to 23 years older than non-COPD controls according to DHEA and GH variation.

Reduction of Premature Aging Markers After Gastric Bypass Surgery in Morbidly Obese Patients.

BACKGROUND: Obesity is considered to be a major comorbidity. Obese patients suffer from an increased proinflammatory state associated with a premature aging phenotype including increased secretion of senescence-associated secretory proteins (SASP) and reduced telomere length. Micro-ribonucleic acids (miRNAs) are non-coding RNA molecules that could modify the post-transcriptional process. Several studies have reported associations between miRNAs and metabolic unhealthy conditions. AIM: To determine if bariatric surgery and the resulting weight loss could reverse the premature aging phenotype. METHODS: We enrolled 58 morbidly obese patients undergoing bariatric surgery. Markers of premature aging including the SASP IL-6, CRP and PAI-1, 7 miRNAs, as well as telomere length and telomere oxidation in mononuclear cells were evaluated. RESULTS: Patients showed a significant drop of body mass index (BMI; 43.98 ± 3.5 versus 28.02 ± 4.1, p < 0.001). We observed a significant reduction in SASP including a reduction of 55% of plasma IL-6 levels (p = 0 < 0.001), 83% of CRP levels (p = 0.001) and 15% of plasma PAI-1 levels (p < 0.001). Telomere length doubled in the patient cohort (p < 0.001) and was accompanied by a reduction in the telomere oxidation index by 70% (p < 0.001). Telomere length was inversely correlated with telomere oxidation. The aging-associated miRNA miR10a_5p was upregulated significantly (p = 0.039), while the other tested miRNAs showed no difference. CONCLUSION: Our data indicate a significant reduction of the proinflammatory SASP after bariatric surgery. We observed an increase in telomere length and reduced oxidative stress at telomeres. miR10a_5p which is downregulated during aging was upregulated after surgery. Overall, bariatric surgery ameliorated the premature aging phenotype.

La infección por VIH como causa de envejecimiento acelerado y fragilidad / HIV infection as a cause of accelerated aging and frailty

La población con infección por VIH está envejeciendo debido al aumento de la supervivencia gracias al tratamiento antirretroviral y al aumento de casos nuevos en personas mayores de 50 años. A pesar de un buen control inmunovirológico tras el tratamiento, el VIH provoca por diferentes vías un estado de inflamación crónica con cambios en el sistema inmunológico similares a los que tienen lugar con el envejecimiento fisiológico dando como resultado el envejecimiento precoz del sistema inmune o inmunosenescencia. Esta inmunosenescencia tiene su manifestación clínica en un aumento de la prevalencia de comorbilidades asociadas a la edad no asociadas al VIH y en un aumento de la prevalencia de fragilidad a edades más tempranas que en la población general. El paciente con infección por VIH es biológicamente mayor de lo que su edad cronológica indica y presenta problemas propios de las personas mayores como la fragilidad que deben ser abordados (AU)

The HIV-infected population is aging due to the success of combination antiretroviral therapy, which prolongs survival, as well as the growing number of newly diagnosed cases in adults 50 years old and over. HIV-infected individuals suffer from an accelerated aging due to the persistent and chronic activation of the immune system that leads to immune exhaustion and accelerated immunosenescence, even when on optimal immuno-virological control treatment. The clinical expression of the immunosenescence state is an increased prevalence of aging-related non-HIV associated comorbidities and a rising prevalence of frailty occurring earlier than in the general population. Thus, HIV-infected patients are biologically older than their chronological age, and they suffer from aging-related problems, such as frailty, which should be assessed (AU)

Hutchinson-Gilford Progeria Syndrome: A Premature Aging Disease.

Progeria is sporadic, very rare, autosomal dominant, deadly childhood disorder. It is one of the progeroid syndromes also known as Hutchinson-Gilford progeria syndrome (HGPS). Aging is a developmental process that begins with fertilization and ends up with death involving a lot of environmental and genetic factors. The disease firstly involves premature aging and then death from complications of atherosclerosis such as myocardial infarction, stroke, atherosclerosis, or heart failure. The lifespan of the patient is normally up to teen age or early twenties. It is usually not inherited because a patient normally dies before the age of reproduction. The most important genetic linkage between progeria and aging is shortening of telomere ends with each replication cycle. The patients are normally observed to have extremely short telomeres. Currently, 90% of the patients are said to have de novo point mutations in the LMNA gene that substitute cytosine with thymine and have been found in individuals with HGPS. Lmna encodes lamins A and C, and the A-type lamins have important structural function in the nuclear envelope. The most common type of HGPS mutation is located at codon 608 (G608G). It could not be diagnosed at birth, but after the age of 2 years, visible, prominent symptoms can be observed. Still, lot of research is needed to solve this mystery; hopefully, future research on HGPS would provide important clues for progeria and other fatal age-related disorders.

Major health impact of accelerated aging in young HIV-infected individuals on antiretroviral therapy.

BACKGROUND: Aging among HIV-infected individuals on antiretroviral therapy (ART) is a significant clinical challenge; however, studies assessing multidimensional aspects of aging are lacking. We characterized 10 geriatric conditions encompassing multiple functional domains, its health impact and associated risk factors in HIV-infected and age-matched uninfected controls. METHODS: HIV-infected individuals were recruited from the outpatient clinic in University Malaya Medical Centre, Malaysia and controls from the community. All participants were aged at least 25 years of age with no acute illness, and HIV-infected individuals were on stable ART. Geriatric conditions were assessed and the burden scored as a composite of geriatric conditions present in an individual (total score = 10). Multivariate regression analysis was performed to determine the risk factors and health impact associated with the burden of geriatric conditions. RESULTS: We analyzed data from 336 HIV-infected individuals (total HIV+), of whom 172 were matched for age, sex, and ethnicity with 172 HIV-uninfected controls (matched subset). In the total HIV-positive cohort, median (interquartile range) age was 44 (38-51) years and CD4 T-cell count was 562 (398-737) cells/µl. The burden of geriatric conditions was significantly higher in the HIV-infected group compared with controls (P < 0.001). With an increasing geriatric condition burden, quality-of-life scores were 2.2-times poorer, healthcare use five times greater, and mortality risk scores four times higher in the HIV-infected group compared with matched controls. Both sociobehavioural and HIV-related clinical factors were independently associated with an increasing burden of geriatric condition in HIV. CONCLUSIONS: A high burden of geriatric conditions with significant impact on health outcomes, including mortality risk scores are observed among HIV-infected individuals on ART in a resource-limited setting.

Kidney disease and aging: A reciprocal relation.

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are overrepresented in elderly patients. This provides specific challenges for the treatment, as the start of dialysis in vulnerable elderly patients may be associated with a rapid decline in functional performance. However, prognosis in elderly patients with ESRD is quite variable and related to the presence of comorbidity and geriatric impairments. The decision to start dialysis in elderly patients should always be based on shared decision making, which may be aided by the use of prediction models which should however not be used to withhold dialysis treatment. The treatment of ESRD in elderly patients should be based on a multidimensional treatment plan with a role for active rehabilitation. Moreover, there also appears to be a reciprocal relationship between aging and CKD, as the presence of geriatric complications is also high in younger patients with ESRD. This has led to the hypothesis of a premature aging process associated with CKD, resulting in different phenotypes such as premature vascular aging, muscle wasting, bone disease, cognitive dysfunction and frailty. Prevention and treatment of this phenotype is based on optimal treatment of CKD, associated comorbidities, and lifestyle factors by established treatments. For the future, interventions, which are developed to combat the aging process in general, might also have relevance for the treatment of patients with CKD, but their role should always be investigated in adequately powered clinical trials, as results obtained in experimental trials may not be directly translatable to the clinical situation of elderly patients. In the meantime, physical exercise is a very important intervention, by improving both physical capacity and functional performance, as well as by a direct effect on the aging process.

Smoking, second-hand smoke exposure and smoking cessation in relation to leukocyte telomere length and mortality.

OBJECTIVES: To investigate the link between smoking exposure, telomere length and mortality, with emphasis on second-hand smoke (SHS) exposure and the duration of smoking cessation. RESULTS: A total of 1,018 participants died during follow-up (mean: 10.3 years). A 50 base-pair decrease in LTL was shown among cotinine-confirmed current versus never smokers. The 90th quantile of LTL decreased with increasing cotinine among never smokers, indicating a role of SHS. Longer telomeres with smoking cessation were indicated but limited to a 3-16 year period of abstaining smoking. When assessing mortality, we observed a lower risk of all-cause death for the second quintile compared to the first among never smokers (HR: 0.67, 95% CI: 0.52-0.87), and a higher risk was found among current smokers (HR: 1.89, 1.19-2.92). MATERIALS AND METHODS: We studied 6,456 nationally representative U.S. respondents with mortality follow-up through to 31 December 2011. Smoking status was assessed by interviews and cotinine levels. Relative leukocyte telomere length (LTL) was quantified by polymerase chain reaction (PCR). Multivariable linear regression was performed to examine LTL by smoking exposure, adjusted for age, sex, race/ethnicity, socioeconomic status, education, body mass index, alcohol consumption, and physical activity. We further estimated the association of LTL with cotinine levels using quantile regression, and with smoking cessation dynamics. Cox regression was used to estimate mortality by smoking status and LTL. CONCLUSION: Our findings indicated a complex association between smoking, telomere length, and mortality. LTL alterations with SHS and smoking cessation warrant further investigation for translation to public health measures.

Envejecimiento e influencia de la inversión del cociente CD4/CD8 en la incidencia de las comorbilidades y mortalidad de una cohorte de pacientes infectados por el virus de inmunodeficiencia humana / Aging and influence of inversion of the CD4: CD8 ratio in the incidence of co-morbidities and mortality in a cohort of patients infected with human immunodeficiency virus

Fundamentos y objetivo. La inversión del cociente CD4/CD8 como indicador de inmunosenescencia puede ser un factor que permita anunciar el riesgo de presentar comorbilidades. Estudiamos la influencia del envejecimiento y de la inversión del cociente CD4/CD8 en la incidencia de comorbilidades y de mortalidad en la cohorte del Hospital Severo Ochoa. Métodos: Analizamos las diferencias en las tasas de incidencia de las comorbilidades ajustadas por la edad y evaluamos la inversión del cociente CD4/CD8 como factor de riesgo para la mortalidad y para el desarrollo de comorbilidades. Resultados: La edad se asoció a un incremento en la tasa de incidencia de diabetes mellitus, fracturas, EPOC y neoplasias no asociadas a sida. Encontramos un mayor riesgo de la tasa de incidencia de episodios clínicos no asociados a sida (OR 2,25; IC 95% 1,025-4,94) y episodios asociados a sida (OR 3,48; IC 95% 1,58-7,64) en los individuos con el cociente CD4/CD8 < 0,7. También los pacientes con un cociente CD4/CD8 < 0,7 presentaron una mayor riesgo de mortalidad (OR 5,96; IC 95% 0,73-48,40). Conclusión: Es importante detectar y prevenir comorbilidades no asociadas a sida en presencia del cociente CD4/CD8 < 0,7 (AU)

Background and objective: It has been postulated that the inversion of the CD4:CD8 ratio as a hallmark of immunosenescence can be an independent factor that can herald the risk of co-morbidities. We studied the influence of aging and inversion of the CD4:CD8 ratio in the incidence of comorbidities and mortality in the cohort of Hosptital Severo Ochoa. Methods: We analyzed the differences in the incidence rates of age-adjusted morbidities and evaluated the inversion of the CD4:CD8 ratio as predictor of mortality and development of comorbidities. Results: Age was associated with an increased incidence rate of diabetes mellitus, fractures, COPD and non-AIDS malignancies. We found an increased incidence rate of non-AIDS clinical events (OR 2.25; 95% CI 1.025-4.94) and AIDS events (OR 3.48; 95% CI 1.58-7.64) in individuals with CD4:CD8 ratio < 0.7. Moreover, patients with a CD4:CD8 ratio < 0.7 ratio had a higher risk of mortality (OR 5.96; 95% CI 0.73 to 48.40). Conclusion: It is important to detect and prevent non-AIDS comorbidities in the presence of a CD4:CD8 ratio < 0.7 (AU)