The mitochondrial respiratory chain (RC) produces most of the cellular ATP and requires strict quality-control mechanisms. To examine RC subunit proteostasis in vivo, we measured RC protein half-lives (HLs) in mice by liquid chromatography-tandem mass spectrometry with metabolic [ 2 H 3 ]-leucine heavy isotope labeling under divergent conditions. We studied 7 tissues/fractions of young and old mice on control diet or one of 2 diet regimens (caloric restriction or rapamycin) that altered protein turnover (42 conditions in total). We observed a 6.5-fold difference in mean HL across tissues and an 11.5-fold difference across all conditions. Normalization to the mean HL of each condition showed that relative HLs were conserved across conditions (Spearman's r = 0.57; P < 10 -4), but were highly heterogeneous between subunits, with a 7.3-fold mean range overall, and a 2.2-to 4.6-fold range within each complex. To identify factors regulating this conserved distribution, we performed statistical analyses to study the correlation of HLs to the properties of the subunits. HLs significantly correlated with localization within the mitochondria, evolutionary origin, location of proteinencoding, and ubiquitination levels. These findings challenge the notion that all subunits in a complex turnover at comparable rates and suggest that there are common rules governing the differential proteolysis of RC protein subunits under divergent cellular conditions.-Karunadharma, P. P., Basisty, N., Chiao, Y. A., Dai, D.-F., Drake, R., Levy, N., Koh, W. J., Emond, M. J., Kruse, S., Marcinek, D., Maccoss, M. J., Rabinovitch, P. S. Respiratory chain protein turnover rates in mice are highly heterogeneous but strikingly conserved across tissues, ages, and treatments. FASEB J. 29, 3582-3592 (2015). www.fasebj.org

BackgroundDespite increasing evidence of a common link between bone and heart health, the relationship between bone mineral density (BMD) and heart failure (HF) risk remains insufficiently studied.Methods and ResultsWe investigated whether BMD measured by dual‐energy x‐ray absorptiometry was associated with incident HF in an older cohort. Cox models were stratified by sex and interactions of BMD with race assessed. BMD was examined at the total hip and femoral neck separately, both continuously and by World Health Organization categories. Of 1250 participants, 442 (55% women) developed HF during the median follow‐up of 10.5 years. In both black and nonblack women, neither total hip nor femoral neck BMD was significantly associated with HF; there was no significant interaction by race. In black and nonblack men, total hip, but not femoral neck, BMD was significantly associated with HF, with evidence of an interaction by race. In nonblack men, lower total hip BMD was associated with higher HF risk (hazard ratio, 1.13 [95% CI, 1.01–1.26] per 0.1 g/cm2 decrement), whereas in black men, lower total hip BMD was associated with lower HF risk (hazard ratio, 0.74 [95% CI, 0.59–0.94]). There were no black men with total hip osteoporosis. Among nonblack men, total hip osteoporosis was associated with higher HF risk (hazard ratio, 2.83 [95% CI, 1.39–5.74]) compared with normal BMD.ConclusionsAmong older adults, lower total hip BMD was associated with higher HF risk in nonblack men but lower risk in black men, with no evidence of an association in women. Further research is needed to replicate these findings and to study potential underlying pathways.

We evaluated the association between two-dimensional (2D) echocardiography (echo) determined myocardial contraction fraction (MCF) and adverse cardiovascular outcomes including incident heart failure (HF), atherosclerotic cardiovascular disease (ASCVD) and mortality. The MCF, the ratio of left ventricular (LV) stroke volume (SV) to myocardial volume (MV), is a volumetric measure of myocardial shortening that can distinguish pathologic from physiologic hypertrophy. Using 2D-echo-guided M-mode data from the Cardiovascular Health Study, we calculated MCF among individuals with LV ejection fraction (EF)≥55%, and used Cox models to evaluate its association with incident HF, ASCVD, and all-cause mortality after adjusting for clinical and echo parameters. We assessed whether log2(SV) and log2(MV) were consistent with the expected 1:−1 ratio used in the definition of MCF. Among 2147 participants (age 72±5), average MCF was 59±13%. After controlling for clinical and echo variables, each 10% absolute increment in MCF was associated with lower risk of HF (HR=0.88; 95% CI=0.82, 0.94), ASCVD (HR=0.90; 95% CI=0.85, 0.95) and death (HR=0.93; 95% CI=0.89, 0.97). Moreover, the MCF was still significantly associated with ASCVD and mortality, but not HF, after adjustment for percent predicted LV mass. Significant departure from the 1:−1 ratio was not observed for ASCVD or death, but did occur for HF, driven by a stronger association for MV than SV. In conclusion, among older adults without CVD or low LVEF, 2D-echo-guided M-mode-derived MCF was independently associated with lower risk of adverse cardiovascular outcomes, but this ratiometric index may not capture the full relationship that is apparent when its components are modeled separately in the case of HF.

We developed micromolded microwell arrays to study the proliferation and senescence of single cells. Microwell arrays were designed to be compatible with conventional cell culture protocols to simplify cell loading, cell culture, and imaging. We demonstrated the utility of these arrays by measuring the proliferation and senescence of isogenic cells which expressed or had been depleted of the human Werner syndrome protein. Our results allowed us to reveal cell-to-cell heterogeneity in proliferation in WRN+ and WRN-depleted fibroblasts during clonal growth.

We created a synthetic cohort of the 1,889 participants who had reached age 90 years at baseline or during follow-up through July 16, 2015. Participants entered the cohort at 90 years of age, and we evaluated their changes in health after age 90 years (median duration of follow-up, 3 years (interquartile range, 1.3-5)). Measures of health included cardiovascular events, cognitive function, depressive symptoms, prescription medications, self-rated health, and functional status. The mortality rate was high: 19.0 per 100 person-years (95% confidence interval : 17.8, 20.3) in women and 20.9 per 100 person-years (95% confidence interval: 19.2, 22.8) in men. Cognitive function and all measures of functional status declined with age; these changes were similar by sex. When we isolated period effects, we found that medication use increased over time. These estimates can help inform future research and can help health-care systems meet the needs of this growing population.

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A safety-net hospital in Boston, Massachusetts, made adaptations to its Nourishing Our Community Program to accommodate restrictions brought on by the COVID-19 pandemic to continue providing food and education to patients. While participation in programs decreased overall, some of the adaptations made, including virtual classes and food pantry home delivery, were well received and are planned to be maintained after the pandemic subsides. By making adjustments to operational procedures, the Nourishing Our Community Program continued to reach its underserved population despite pandemic challenges. (Am J Public Health. Published online ahead of print February 18, 2021: e1–e4. https://doi.org/10.2105/AJPH.2020.306132 )

From 2010 to 2050, the number of people 90 years or older in the United States is projected to more than quadruple and comprise 10% of the 65 years or older population. 1 There is limited information, however, about the health and functional status of such individuals. The Cardiovascular Health Study (CHS), which began in 1989, is a federally funded observational community-based study of risk factors for cardiovascular disease in people 65 years and older. The healthy participant bias in the study has attenuated over time, and retention has remained high throughout followup, even for the oldest participants. 2,3 We describe the health and functional status of participants at age 90 years.