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Lysine-specific demethylase hairless (EC 1.14.11.65) ([histone H3]-dimethyl-L-lysine(9) demethylase hairless)

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Patients with hip fracture and total hip arthroplasty surgery differ in anthropometric, but not cardiovascular screening abnormalities.

With the rising number of hip surgeries, simple and cost-effective tools for surgery risk assessment are warranted. The analysis of heart rate variability (HRV) may not only provide critical insights into the general frailty of patients with hip surgery, but also allow for better differentiation of health profiles in different hip surgery groups. Using HRV analysis, the present study compared cardiovascular as well as anthropometric parameters between patients with hip surgery, the hip fracture surgery group (HFS) and the total hip arthroplasty group (THA), and a control group. 71 participants (56.3% women), aged 60-85 years, took part, divided into three groups-patients after hip surgery (21 HFS and 30 THA patients) and a control group (20 participants). Electrocardiogram was recorded at baseline and after the application of a physical stressor (grip strength). A 3 (group) × 2 (time) repeated measures ANOVA, and a chi square test were carried out to test for group differences. Higher weight (p = .002), body mass index (p = .001), and systolic blood pressure (p = .034) were found in THA patients compared to HFS patients. Lower calf circumference (p = .009) and diastolic blood pressure (p = .048) were observed for the HFS group compared to the control group. For cardiovascular parameters, significant differences emerged between the HFS group and the control group in HR (p = .005), SDNN (p = .034) and SD2 (p = .012). No significant differences in cardiovascular parameters were observed between the two hip surgery groups: neither at baseline nor during stressor recovery. While HRV seems to differentiate well between HFS patients and controls, more research with larger samples is needed to scrutinize similaritites and differences in cardiovascular profiles between HFS and THA patients.


Keywords

  • Aging
  • Cardiovascular reactivity
  • Heart rate variability
  • Hip fracture
  • Total hip arthroplasty


Clinical Role of Lung Ultrasound for the Diagnosis and Prognosis of Coronavirus Disease Pneumonia in Elderly Patients: A Pivotal Study.

Lung ultrasound (LUS) showed a promising role in the diagnosis and monitoring of patients hospitalized for novel coronavirus disease (COVID-19). However, no data are available on its role in elderly patients. The aim of this study was to evaluate the diagnostic and prognostic role of LUS in elderly patients hospitalized for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pneumonia. Consecutive elderly patients (age >65 years) hospitalized for COVID-19 were enrolled. Demographics, laboratory, comorbidity, and the clinical features of the patients were collected. All patients underwent LUS on admission to the ward. LUS characteristics have been analyzed. Uni- and multivariate analyses to evaluate predictors for in-hospital death were performed. Thirty-seven hospitalized elderly patients (19 men) with a diagnosis of SARS-CoV-2 infection were consecutively enrolled. The median age was 82 years (interquartile range 74.5-93.5). Ultrasound alterations were found in all patients enrolled; inhomogeneous interstitial syndrome with spared areas (91.9%) and pleural alterations (100%) were the most frequent findings. At univariate analysis, LUS score (hazard ratio [[[HR]]] 1.168, 95% CI 1.049-1.301) and pleural effusions (HR 3.995, 95% CI 1.056-15.110) were associated with in-hospital death. At multivariate analysis, only LUS score (HR 1.168, 95% CI 1.049-1.301) was independelty associated with in-hospital death. The LUS score's best cutoff for distinguishing patients experiencing in-hospital death was 17 (at multivariate analysis LUS score ≥17, HR 4.827, 95% CI 1.452-16.040). In-hospital death was significantly different according to the LUS score cutoff of 17 (p = 0.0046). LUS could play a role in the diagnosis and prognosis in elderly patients hospitalized for SARS-CoV-2 infection.


Keywords

  • Aging
  • Coronavirus disease
  • Elderly
  • Lung ultrasound
  • Severe acute respiratory syndrome-coronavirus-2


The Relationship of Accelerometer-Assessed Standing Time With and Without Ambulation and Mortality: The WHI OPACH Study.

Self-reported time spent standing has been associated with lower risk of mortality. No previous studies have examined this association using device-measured standing. This was a prospective cohort study of 5878 older (median age = 80 years), racial/ethnically diverse, community-dwelling women in the WHI Objective Physical Activity and Cardiovascular Health Study (OPACH). Women wore accelerometers for 1 week and were followed for mortality. The study applied previously validated machine learning algorithms to ActiGraph GT3X accelerometer data to separately measure time spent standing with and without ambulation. Cox proportional hazards models were used to estimate mortality risk adjusting for potential confounders. Effect modification by age, body mass index, moderate-to-vigorous physical activity, sedentary time, physical functioning, and race/ethnicity was evaluated. There were 691 deaths during 26 649 person-years of follow-up through March 31, 2018 (mean follow-up = 4.8 years). In fully adjusted models, all-cause mortality risk was lower among those with more standing without ambulation (quartile [Q] 4 vs Q1 HR = 0.63; 95% CI = 0.49-0.81, p-trend = .003) and more standing with ambulation (Q4 vs Q1 HR = 0.50; 95% CI = 0.35-0.71, p-trend < .001). Associations of standing with ambulation and mortality were stronger among women with above-median sedentary time (HR = 0.51; 95% CI = 0.38-0.68) compared to women with below-median sedentary time (HR = 0.80; 95% CI = 0.59-1.07; p-interaction = .02). In this prospective study among older women, higher levels of accelerometer-measured standing were associated with lower risks of all-cause mortality. Standing is an achievable approach to interrupting prolonged sedentary time, and if not contraindicated, is a safe and feasible behavior that appears to benefit health in older ages.


Keywords

  • Accelerometer
  • Longevity
  • Physical activity


Age-related myofiber atrophy in old mice is reversed by ten weeks voluntary high-resistance wheel running.

Age-related loss of muscle mass and function can be attenuated in rodents with life-long voluntary wheel running with moderate resistance. The present study assessed if sarcopenia could be counteracted with ten weeks high intensity training. Old (22-23 months) and middle-aged (11 months) mice were divided into three physical activity groups: Ten weeks of voluntary running in wheels with high (HR) or low resistance (LR), or no running wheel (SED). The wheel resistance was 0.5-1.5 g in the LR group and progressed from 5 g to 10 g in the HR group. Six, 8 and 5 old and 8, 9 and 9 middle-aged mice of the SED, LR and HR groups, respectively, were included in the analysis. Wheel activity was monitored throughout the intervention. Muscle mass of the tibialis anterior, gastrocnemius, soleus and plantaris muscles were measured post-mortem. Fiber type distribution and myofiber cross sectional areal (CSA) were quantified in the gastrocnemius and soleus muscles as well as total number of fibers in the soleus muscle. In the SED, the mass of all individual muscles was reduced in the old vs middle-aged (P < 0.001). In the training groups, the old mice ran significantly less, slower and for shorter bouts than the middle-aged throughout the intervention (P < 0.05). HR running increased the gastrocnemius and soleus muscle mass by 6% and 18% respectively in the old compared to SED. Fiber CSA was significantly reduced in the old SED mice, whereas fiber CSA in the old HR gastrocnemius and soleus muscles was comparable to the SED middle-aged. Fiber type shifted from 2b towards 2a in the gastrocnemius muscle of the trained old mice. HR running was more efficient than LR in maintaining muscle mass and myofiber size, and in shifting fiber types. In the middle-aged mice, similar effects were found, but less pronounced. Interestingly, fiber CSA was unaffected by running in the middle-aged. Ten weeks of HR running had a positive effect on muscle mass and morphology in both middle-aged and old mice. The old HR fiber CSA was greater than in old SED and comparable to the middle-aged, and the fibers shifted to a more oxidative composition (2b → 2a). Albeit less pronounced, similar training effects were observed in the middle-aged mice despite running faster and longer than the old.


Keywords

  • Aging
  • Exercise
  • Mouse model
  • Muscle morphology
  • Skeletal muscle
  • Training


Relationship between Oxygen Uptake, Heart Rate, and Perceived Effort in an Aquatic Incremental Test in Older Women.

Different parameters can be used to control the intensity of aerobic exercises, a choice that should consider the population and exercise environment targeted. Therefore, our study aimed to verify the relationship between oxygen uptake (VO ), heart rate (HR), rating of perceived exertion (RPE), and cadence during an aquatic incremental test in older women. Nine older women (64.3 ± 4.4 years) engaged in a water-based aerobic training performed an aquatic incremental test using the stationary running exercise (cadence increases of 15 b·min every 2 min) until participants' volitional exhaustion. VO , HR, and RPE data were measured, and the percentage of peak VO (%VO ) and percentage of maximal HR (%HR ) were calculated. Linear and polynomial regression analyses were performed (α = 0.05). Polynomial regressions revealed the best adjustments for all analyses. Data showed a significant relationship ([i]p[/i] < 0.001) between %VO and %HR ([i]r[/i] = 0.921), %VO and RPE ([i]r[/i] = 0.870), and %HR and RPE ([i]r[/i] = 0.878). Likewise, significant relationships between cadence ([i]p[/i] < 0.001) and %VO ([i]r[/i] = 0.873), %HR ([i]r[/i] = 0.874), and RPE ([i]r[/i] = 0.910) were also observed. In summary, the physiological, subjective, and mechanical variables investigated were highly associated during an aquatic incremental test to exhaustion in older women. Therefore, these different parameters can be employed to adequately prescribe water-based programs according to preference and availability.


Keywords

  • aging
  • cardiorespiratory
  • maximum test
  • rate of perceived exertion
  • water aerobics
  • water-based exercises


Predicted Skeletal Muscle Mass and 4-Year Cardiovascular Disease Incidence in Middle-Aged and Elderly Participants of IKARIA Prospective Epidemiological Study: The Mediating Effect of Sex and Cardiometabolic Factors.

The sex-specific effect of skeletal muscle mass (SMM) index (SMI) on 4-year first fatal/non-fatal cardiovascular disease (CVD) event in free-of-disease individuals was examined. In 2009, [i]n[/i] = 1411 inhabitants (mean age = 64(12)) from Ikaria were selected. Follow-up was performed in 2013. SMI was created to reflect SMM through appendicular skeletal muscle mass (indirectly calculated through formulas) divided by body mass index (BMI). Fifteen and six tenths percent of participants exhibited CVD (19.8% in men/12% in women, p = 0.002). Significant U-shape trends were observed in participants >65 years old and women irrespective to age confirmed through multi-adjusted Cox regression analysis; in age >65 years, Hazard Ratio (HR) = 0.80, 95% Confidence Interval (95%CI) (0.45, 0.96) and in women HR = 0.71, 95% CI (0.33, 0.95), while, as for the 3rd SMI tertile, no significant trends were observed. Mediation analysis revealed that mediators of the aforementioned associations in men were the arterial distensibility and total testosterone, while, in women, inflammation, insulin resistance, and arterial distensibility. High SMM accompanied by obesity may not guarantee lower CVD risk. Specific cardiometabolic factors seem to explain this need for balance between lean and fat mass.


Keywords

  • aging
  • body composition
  • gender
  • heart disease
  • lean mass
  • obesity
  • primary prevention
  • women


Obesity is associated with early hip fracture risk in postmenopausal women: a 25-year follow-up.

Association of body mass index and hip fracture has been controversial. In this study, women with lowest and highest body weight had the highest fracture incidence. A 25-year follow-up indicated that obesity associates with early hip fracture risk and suggested increasing trend in normal-weight women at a later stage. Obesity is a pandemic health issue. Its association with hip fracture risk remains controversial. We studied the long-term relationship of body mass index and hip fracture incidence in postmenopausal women. The cohort of 12,715 Finnish women born in 1932-1941 was followed for 25 years, covering ages from 58 up to 83. Fractures and deaths were obtained from national registries. Women were investigated in deciles of BMI as well as in WHO weight categories (normal, overweight, or obese). The follow-up analysis was carried out in two age strata as "early" (58-70 years) and "late" (> 70 years). Body weight information was updated accordingly. Femoral neck BMD was recorded for a subsample (n = 3163). Altogether, 427 hip fractures were observed. A higher risk of early hip fracture was observed in obese and normal-weight compared with overweight women with hazard ratios (HRs) of 2.3 ((95% CI) 1.4-3.7) and 2.0 (1.3-3.1) while no difference was observed in late hip fracture risk between the three WHO categories (log rank p = 0.14). All-cause mortality during the follow-up was 19.3%. Compared with normal weight women, the obese women had a higher risk of death with an HR of 1.6 (1.4-1.8) and higher baseline BMD (p < 0.001). Faster bone loss was observed in the obese compared with other women (p < 0.001). Obesity associates with earlier hip fracture and higher postfracture mortality. The obese women with low BMD have clearly the highest risk of hip fracture. This combination increases hip fracture risk more than either of the factors alone. After 75 years of age, risk appears to increase more in normal weight women, but this trend is in need of further confirmation.


Keywords

  • Aging
  • Body mass index
  • Bone mineral density
  • Follow-up study
  • General population
  • Hip fracture
  • Menopause
  • Obesity


ATM inhibition synergizes with fenofibrate in high grade serous ovarian cancer cells.

While therapies targeting deficiencies in the homologous recombination (HR) pathway are emerging as the standard treatment for high grade serous ovarian cancer (HGSOC) patients, this strategy is limited to the ~50% of patients with a deficiency in this pathway. Therefore, patients with HR-proficient tumors are likely to be resistant to these therapies and require alternative strategies. We found that the HR gene Ataxia Telangiectasia Mutated (ATM) is wildtype and its activity is upregulated in HGSOC compared to normal fallopian tube tissue. Interestingly, multiple pathways related to metabolism are inversely correlated with [i]ATM[/i] expression in HGSOC specimens, suggesting that combining ATM inhibition with metabolic drugs would be effective. Analysis of FDA-approved drugs from the Dependency Map demonstrated that ATM-low cells are more sensitive to fenofibrate, a PPARα agonist that affects multiple cellular metabolic pathways. Consistently, PPARα signaling is associated with [i]ATM[/i] expression. We validated that combined inhibition of ATM and treatment with fenofibrate is synergistic in multiple HGSOC cell lines by inducing senescence. Together, our results suggest that metabolic changes induced by ATM inhibitors are a potential target for the treatment of HGSOC.


Keywords

  • Biochemistry
  • Bioinformatics
  • Cancer research
  • Cell biology
  • Cellular metabolism
  • Cellular senescence
  • Drug combinations
  • Homologous recombination
  • Metabolite
  • Molecular biology
  • PPARa


Effectiveness of adjuvant FOLFOX vs 5FU/LV in adults over age 65 with stage II and III colon cancer using a novel hybrid approach.

Estimates of cancer therapy effects can differ in clinical trials and clinical practice, partly due to underrepresentation of certain patient subgroups in trials. We utilize a hybrid approach, combining clinical trial and real-world data, to estimate the comparative effectiveness of two adjuvant chemotherapy regimens for colon cancer. We identified patients aged 66 and older enrolled in the Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer. Similar patients were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, initiating adjuvant chemotherapy with either 5-fluorouracil (5FU) alone or in combination with oxaliplatin (FOLFOX). We used logistic regression to estimate the likelihood of trial enrollment as a function of age, sex, and substage. Using inverse odds of sampling weights (IOSW), we compared 5-year mortality in patients randomized to FOLFOX vs 5FU using weighted Cox proportional hazards regression, the Nelson-Aalen estimator for cumulative hazards, and bootstrapping for 95% confidence intervals (CIs). There were 690 trial participants and 3834 SEER-Medicare patients. The SEER-Medicare population was older and had a higher proportion of stage IIIB and IIIC patients than the trial. After controlling for differences between populations, the IOSW 5-year HR was 1.21 (0.89, 1.65), slightly farther from the null than the trial estimate (HR = 1.14, 95%CI: 0.87, 1.49). This study supports mounting evidence of little to no incremental reduction in 5-year mortality for FOLFOX vs 5FU in older adults with stage II-III colon cancer, emphasizing the importance of combining clinical trial and real-world data to support such conclusions.


Keywords

  • aging
  • cancer
  • chemotherapy
  • comparative effectiveness research
  • pharmacoepidemiology


Cortical thickness and resting-state cardiac function across the lifespan: A cross-sectional pooled mega-analysis.

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [[[HR]]] and its variability [[[HR]]V] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.


Keywords

  • aging
  • autonomic nervous system
  • cortical thickness
  • heart rate
  • heart rate variability
  • sex


Age, Frailty, and Comorbidity as Prognostic Factors for Short-Term Outcomes in Patients With Coronavirus Disease 2019 in Geriatric Care.

To analyze whether frailty and comorbidities are associated with in-hospital mortality and discharge to home in older adults hospitalized for coronavirus disease 2019 (COVID-19). Single-center observational study. Patients admitted to geriatric care in a large hospital in Sweden between March 1 and June 11, 2020; 250 were treated for COVID-19 and 717 for other diagnoses. COVID-19 diagnosis was clinically confirmed by positive reverse transcription polymerase chain reaction test or, if negative, by other methods. Patient data were extracted from electronic medical records, which included Clinical Frailty Scale (CFS), and were further used for assessments of the Hospital Frailty Risk Score (HFRS) and the Charlson Comorbidity Index (CCI). In-hospital mortality and home discharge were followed up for up to 25 and 28 days, respectively. Multivariate Cox regression models adjusted for age and sex were used. Among the patients with COVID-19, in-hospital mortality rate was 24% and home discharge rate was 44%. Higher age was associated with in-hospital mortality (hazard ratio [[[HR]]] 1.05 per each year, 95% confidence interval [CI] 1.01‒1.08) and lower probability of home discharge (HR 0.97, 95% CI 0.95‒0.99). CFS (>5) and CCI, but not HFRS, were predictive of in-hospital mortality (HR 1.93, 95% CI 1.02‒3.65 and HR 1.27, 95% CI 1.02‒1.58, respectively). Patients with CFS >5 had a lower probability of being discharged home (HR 0.38, 95% CI 0.25‒0.58). CCI and HFRS were not associated with home discharge. In general, effects were more pronounced in men. Acute kidney injury was associated with in-hospital mortality and hypertension with discharge to home. Other comorbidities (diabetes, cardiovascular disease, lung diseases, chronic kidney disease and dementia) were not associated with either outcome. Of all geriatric patients with COVID-19, 3 out of 4 survived during the study period. Our results indicate that in addition to age, the level of frailty is a useful predictor of short-term COVID-19 outcomes in geriatric patients.

MeSH Terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Betacoronavirus
  • COVID-19
  • Comorbidity
  • Coronavirus Infections
  • Female
  • Frail Elderly
  • Geriatrics
  • Humans
  • Male
  • Models, Statistical
  • Outcome Assessment, Health Care
  • Pandemics
  • Pneumonia, Viral
  • Prognosis
  • SARS-CoV-2
  • Survival Analysis
  • Sweden

Keywords

  • COVID-19
  • aging
  • comorbidity
  • frailty
  • geriatrics
  • survival


Short-Term Effect of Self-Selected Training Intensity on Ambulatory Blood Pressure in Hypertensive Older Women: A Randomized Controlled Trial.

To investigate the short-term effect of self-selected training intensity (SSTI) on ambulatory blood pressure (BP) in hypertensive older women. This is a randomized, single-blind, two-arm, parallel-group controlled trial that included 40 medicated hypertensive older women (64.4±3.6 years; resting systolic 118±19 and diastolic BP 68±9 mmHg). SSTI intervention was performed three times per week, 30-50 minutes per session (n=20). The control group participated in health education meetings once per week (n=20). Ambulatory BP (primary outcome) and six-minute walking test performance (secondary outcome) were assessed at baseline and following 8 weeks of intervention. Heart rate (HR), rating of perceived exertion (RPE, 6-20), and affective valence (ie, feeling scale, -5/ 5) were recorded during all SSTI sessions. Intention-to-treat and per-protocol analyses were used for data analyses. Fifteen participants from the SSTI group and 17 from the control group completed the study. No differences in ambulatory BP (24-h, awake, and asleep) were observed between SSTI and control groups (intention-to-treat and per-protocol analyses; p>0.05). The SSTI group showed a greater six-minute walking test performance than the control group in the intention-to-treat and per-protocol analyses (p<0.05). The participants exercised at 52±10% of HR reserve reported an RPE of 11±1 and an affective valence of 3.4±1.1 over the 8-week period. SSTI is a feasible approach to induce a more active lifestyle and increase health-related fitness in hypertensive older women, although it does not improve BP control over a short-term period.


Keywords

  • aging
  • exercise
  • hypertension


Clinical and demographic parameters predict the progression from mild cognitive impairment to dementia in elderly patients.

To evaluate the possibility of predicting the risk of progression from mild cognitive impairment (MCI) to dementia using a combination of clinical/demographic parameters. A total of 462 MCI elderly patients (follow-up: 33 months). Variable measured included cognitive functions, age, gender, MCI type, education, comorbidities, clinical chemistry, and functional status. Amnestic type (aMCI) represented 63% of the sample, non-amnestic (naMCI) 37%; 190 subjects progressed to dementia, 49% among aMCI, and 28% among naMCI. At Cox multivariate regression analysis, only MMSE (one point increase HR 0.84; 95% CI 0.79-0.90), aMCI (HR 2.35; 95% CI 1.39-3.98), and age (1 year increase HR 1.05; 95% CI 1.01-1.10) were independently associated with progression to dementia. A score was created based on these dichotomized variables (score 0-3): age (≥ or < 78 years), MMSE score (≥ or < 25/30) and aMCI type. The conversion rate progressed from 6% in subjects with score 0 (negative predictive value: 0.94), to 31% in individuals with score 1, to 53% in subjects with score 2, to 72% in individuals with score 3 (positive predictive value: 0.72). ROC curve analysis showed an area under the curve of 0.72 (95% CI 0.66-0.75, p 0.0001). We have described a simple score, based on previously recognized predictors such as age, MMSE, and MCI type, which may be useful for an initial stratification of the risk of progression to dementia in patients affected by MCI. The score might help the clinicians to evaluate the need for more expansive/invasive examinations and for a closer follow-up in MCI patients.


Keywords

  • Aging
  • Cox regression
  • Dementia
  • Follow-up
  • Mild cognitive impairment


Senescence Induction by Combined Ionizing Radiation and DNA Damage Response Inhibitors in Head and Neck Squamous Cell Carcinoma Cells.

DNA damage response inhibitors (DDRi) may selectively enhance the inactivation of tumor cells in combination with ionizing radiation (IR). The induction of senescence may be the key mechanism of tumor cell inactivation in this combinatorial treatment. In the current study the effect of combined IR with DDRi on the induction of senescence was studied in head and neck squamous cell carcinoma (HNSCC) cells with different human papilloma virus (HPV) status. The integrity of homologous recombination (HR) was assessed in two HPV positive, two HPV negative HNSCC, and two healthy fibroblast cell cultures. Cells were treated with the DDRi CC-115 (DNA-dependent protein kinase, DNA-pK; dual mammalian target of rapamycin, mTor), VE-822 (ATR; ataxia telangiectasia and Rad3-related kinase), and AZD0156 (ATM; ataxia telangiectasia mutated kinase) combined with IR. Effects on senescence, apoptosis, necrosis, and cell cycle were analyzed by flow cytometry. The fibroblast cell lines generally tolerated IR or combined treatment better than the tumor cell lines. The ATM and ATR inhibitors were effectively inducing senescence when combined with IR. The DNA-PK inhibitor was not an important inductor of senescence. HPV status and HR activity had a limited influence on the efficacy of DDRi. Induction of senescence and necrosis varied individually among the cell lines due to molecular heterogeneity and the involvement of DNA damage response pathways in senescence induction.


Keywords

  • ATM
  • ATR
  • DNA damage response inhibitor
  • DNAPK
  • HNSCC
  • homologous recombination
  • ionizing radiation
  • kinase inhibitor
  • radiosensitivity
  • senescence


Plasma Dehydroepiandrosterone Sulfate and Cardiovascular Disease Risk in Older Men and Women.

Lower dehydroepiandrosterone-sulfate (DHEA-S) levels have been inconsistently associated with coronary heart disease (CHD) and mortality. Data are limited for heart failure (HF) and association between DHEA-S change and events. Assess associations between low DHEA-S/DHEA-S change and incident HF hospitalization, CHD, and mortality in older adults. DHEA-S was measured in stored plasma from visits 4 (1996-1998) and 5 (2011-2013) of the Atherosclerosis Risk in Communities study. Follow-up for incident events: 18 years for DHEA-S level; 5.5 years for DHEA-S change. General community. Individuals without prevalent cardiovascular disease (n = 8143, mean age 63 years). Associations between DHEA-S and incident HF hospitalization, CHD, or mortality; associations between 15-year change in DHEA-S (n = 3706) and cardiovascular events. DHEA-S below the 15th sex-specific percentile of the study population (men: 55.4 µg/dL; women: 27.4 µg/dL) was associated with increased HF hospitalization (men: hazard ratio [[[HR]]] 1.30, 95% confidence interval [CI], 1.07-1.58; women: HR 1.42, 95% CI, 1.13-1.79); DHEA-S below the 25th sex-specific percentile (men: 70.0 µg/dL; women: 37.1 µg/dL) was associated with increased death (men: HR 1.12, 95% CI, 1.01-1.25; women: HR 1.19, 95% CI, 1.03-1.37). In men, but not women, greater percentage decrease in DHEA-S was associated with increased HF hospitalization (HR 1.94, 95% CI, 1.11-3.39). Low DHEA-S and change in DHEA-S were not associated with incident CHD. Low DHEA-S is associated with increased risk for HF and mortality but not CHD. Further investigation is warranted to evaluate mechanisms underlying these associations.


Keywords

  • DHEA-S
  • aging
  • heart failure
  • mortality

{{medline-entry |title=High intensity interval training combined with L-citrulline supplementation: Effects on physical performance in healthy older adults. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32721549 |abstract=The aim of this study was to evaluate the effect of citrulline (CIT) supplementation combined to high intensity interval training (HIIT) on physical performance in healthy older adults. This study is a secondary analysis from a double-blind, randomized trial. Among the participants (sedentary