ChatGPT's Role in Gerontology Research.

BACKGROUND: ChatGPT and other ChatBots have emerged as tools for interacting with information in manners resembling natural human speech. Consequently, the technology is used across various disciplines, including business, education, and even in biomedical sciences. There is a need to better understand how ChatGPT can be used to advance gerontology research. Therefore, we evaluated ChatGPT responses to questions on specific topics in gerontology research, and brainstormed recommendations for its use in the field. METHODS: We conducted semi-structured brainstorming sessions to identify uses of ChatGPT in gerontology research. We divided a team of multidisciplinary researchers into four topical groups: a) gero-clinical science, b) basic geroscience, c) informatics as it relates to electronic health records (EHR), and d) gero-technology. Each group prompted ChatGPT on a theory-, methods-, and interpretation-based question and rated responses for accuracy and completeness based on standardized scales. RESULTS: ChatGPT responses were rated by all groups as generally accurate. However, the completeness of responses was rated lower, except by members of the informatics group, who rated responses as highly comprehensive. CONCLUSIONS: ChatGPT accurately depicts some major concepts in gerontological research. However, researchers have an important role in critically appraising the completeness of its responses. Having a single generalized resource like ChatGPT may help summarize the preponderance of evidence in the field to identify gaps in knowledge and promote cross-disciplinary collaboration.

Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial.

People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. -10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed.

Resveratrol impinges on retrograde communication without inducing mitochondrial biogenesis in aged rat soleus muscle.

The natural polyphenol resveratrol (RSV) might counteract the skeletal muscle age-related loss of muscle mass and strength/function partly acting on mitochondria. This work analysed the effects of a six-week administration of RSV (50 mg/kg/day) in the oxidative Soleus (Sol) skeletal muscle of old rats (27 months old). RSV effects on key mitochondrial biogenesis proteins led to un unchanged amount of SIRT1 protein and a marked decrease (60 %) in PGC-1α protein. In addition, Peroxyredoxin 3 (PRXIII) protein decreased by 50 %, which on overall suggested the absence of induction of mitochondrial biogenesis by RSV in old Sol. A novel direct correlation between PGC-1α and PRXIII proteins was demonstrated by correlation analysis in RSV and ad-libitum (AL) rats, supporting the reciprocally coordinated expression of the proteins. RSV supplementation led to an unexpected 50 % increase in the frequency of the oxidized base OH8dG in mtDNA. Furthermore, RSV supplementation induced a 50 % increase in the DRP1 protein of mitochondrial dynamics. In both rat groups an inverse correlation between PGC-1α and the frequency of OH8dG as well as an inverse correlation between PRXIII and the frequency of OH8dG were also found, suggestive of a relationship between oxidative damage to mtDNA and mitochondrial biogenesis activity. Such results may indicate that the antioxidant activity of RSV in aged Sol impinged on the oxidative fiber-specific, ROS-mediated, retrograde communication, thereby affecting the expression of SIRT1, PGC-1α and PRXIII, reducing the compensatory responses to the age-related mitochondrial oxidative stress and decline.

The Lipid Intensive Drug Therapy for Sepsis Phase II Pilot Clinical Trial.

OBJECTIVES: Low cholesterol levels in early sepsis patients are associated with mortality. We sought to test if IV lipid emulsion administration to sepsis patients with low cholesterol levels would prevent a decline or increase total cholesterol levels at 48 hours. DESIGN: Phase II, adaptive, randomized pilot clinical trial powered for 48 patients. SETTING: Emergency department or ICU of an academic medical center. PATIENTS: Sepsis patients (first 24 hr) with Sequential Organ Failure Assessment greater than or equal to 4 or shock. INTERVENTIONS: Patients meeting study criteria, including screening total cholesterol levels less than or equal to 100 mg/dL or high-density lipoprotein cholesterol (HDL-C) + low-density lipoprotein cholesterol (LDL-C) less than or equal to 70 mg/dL, were randomized to receive one of three doses of lipid emulsion administered twice in 48 hours or no drug (controls). The primary endpoint was a change in serum total cholesterol (48 hr - enrollment) between groups. MEASUREMENTS AND MAIN RESULTS: Forty-nine patients were enrolled and randomized. Two patients randomized to lipid emulsion were withdrawn before drug administration. Data for 24 control patients and 23 lipid emulsion patients were analyzed. The mean change in total cholesterol from enrollment to 48 hours was not different between groups and was 5 mg/dL ( sd 20) for lipid emulsion patients, and 2 mg/dL ( sd 18) for control patients ( p = 0.62). The mean changes in HDL-C and LDL-C were similar between groups. Mean change in triglycerides was elevated in lipid emulsion patients (61 mg/dL, sd 87) compared with controls (20 mg/dL, sd 70, p = 0.086). The 48-hour change in SOFA score was -2 (interquartile range [IQR] -4, -1) for control patients and -2 (IQR -3, 0) for lipid emulsion patients ( p = 0.46). CONCLUSIONS: Administration of IV lipid emulsion to early sepsis patients with low cholesterol levels did not influence change in cholesterol levels from enrollment to 48 hours.

Iron homeostasis in older adults: balancing nutritional requirements and health risks.

Iron plays a crucial role in many physiological processes, including oxygen transport, bioenergetics, and immune function. Iron is assimilated from food and also recycled from senescent red blood cells. Iron exists in two dietary forms: heme (animal based) and non-heme (mostly plant based). The body uses iron for metabolic purposes, and stores the excess mainly in splenic and hepatic macrophages. Physiologically, iron excretion in humans is inefficient and not highly regulated, so regulation of intestinal absorption maintains iron homeostasis. Iron losses occur at a steady rate via turnover of the intestinal epithelium, blood loss, and exfoliation of dead skin cells, but overall iron homeostasis is tightly controlled at cellular and systemic levels. Aging can have a profound impact on iron homeostasis and induce a dyshomeostasis where iron deficiency or overload (sometimes both simultaneously) can occur, potentially leading to several disorders and pathologies. To maintain physiologically balanced iron levels, reduce risk of disease, and promote healthy aging, it is advisable for older adults to follow recommended daily intake guidelines and periodically assess iron levels. Clinicians can evaluate body iron status using different techniques but selecting an assessment method primarily depends on the condition being examined. This review provides a comprehensive overview of the forms, sources, and metabolism of dietary iron, associated disorders of iron dyshomeostasis, assessment of iron levels in older adults, and nutritional guidelines and strategies to maintain iron balance in older adults.

Microbiome interactions with different risk factors in development of myocardial infarction.

Among all non-communicable diseases, Cardiovascular Diseases (CVDs) stand as the leading global cause of mortality. Within this spectrum, Myocardial Infarction (MI) strikingly accounts for over 15 % of all deaths. The intricate web of risk factors for MI, comprising family history, tobacco use, oral health, hypertension, nutritional pattern, and microbial infections, is firmly influenced by the human gut and oral microbiota, their diversity, richness, and dysbiosis, along with their respective metabolites. Host genetic factors, especially allelic variations in signaling and inflammatory markers, greatly affect the progression or severity of the disease. Despite the established significance of the human microbiome-nutrient-metabolite interplay in associations with CVDs, the unexplored terrain of the gut-heart-oral axis has risen as a critical knowledge gap. Moreover, the pivotal role of the microbiome and the complex interplay with host genetics, compounded by age-related changes, emerges as an area of vital importance in the development of MI. In addition, a distinctive disease susceptibility and severity influenced by gender-based or ancestral differences, adds a crucial insights to the association with increased mortality. Here, we aimed to provide an overview on interactions of microbiome (oral and gut) with major risk factors (tobacco use, alcohol consumption, diet, hypertension host genetics, gender, and aging) in the development of MI and therapeutic regulation.

Use of Minimally Invasive Methods to Assess Fuel Utilization and Circadian Rhythms in Older Adults.

Aging is associated with multiple physiological changes that contribute synergistically and independently to physical disability and the risk of chronic disease. Although the etiology of age-related physical disability is complex and multifactorial, the decline in mitochondrial function appears to coincide with the progression of functional decline in many older adults. The reason why there is a decrease in mitochondrial function with aging remains elusive, but emerging science indicates that both fuel metabolism and circadian rhythms can influence mitochondrial function. Recent studies have established that circadian rhythms become disturbed with aging, and that disrupted circadian rhythms have pathological consequences that impact mitochondrial function and overlap with many age-associated chronic diseases. Current quantitative methods for direct assessment of mitochondrial function are invasive and typically require a muscle biopsy, which can pose difficulties with participant recruitment and study adherence, given the perceived levels of potential pain and risk. Thus, an innovative and relatively noninvasive protocol to assess changes in mitochondrial function at the cellular level and circadian patterns in older adults was adapted. Specifically, a real-time metabolic flux analyzer is used to assess the mitochondrial bioenergetic function of white blood cells under differential substrate availability. The expression of circadian clock genes in white blood cells to cross-correlate with the mitochondrial bioenergetics and circadian rhythm outcomes are also analyzed. It is believed that these innovative methodological approaches will aid future clinical trials by providing minimally invasive methods for studying mitochondrial substrate preference and circadian rhythms in older adults.

Biomarkers of Cellular Senescence Predict the Onset of Mobility Disability and Are Reduced by Physical Activity in Older Adults.

Studies in mice and cross-sectional studies in humans support the premise that cellular senescence is a contributing mechanism to age-associated deficits in physical function. We tested the hypotheses that circulating proteins secreted by senescent cells are (i) associated with the incidence of major mobility disability (MMD), the development of persistent mobility disability (PMMD), and decrements in physical functioning in older adults, and (ii) influenced by physical activity (PA). Using samples and data obtained longitudinally from the Lifestyle Interventions in Elders Study clinical trial, we measured a panel of 27 proteins secreted by senescent cells. Among 1 377 women and men randomized to either a structured PA intervention or a healthy aging (HA) intervention, we observed significant associations between several senescence biomarkers, most distinctly vascular endothelial growth factor A (VEGFA), tumor necrosis factor receptor 1 (TNFR1), and matrix metallopeptidase 7 (MMP7), and the onset of both MMD and PMMD. Moreover, VEGFA, GDF15, osteopontin, and other senescence biomarkers were associated with reductions in short physical performance battery scores. The change in senescence biomarkers did not differ between PA and HA participants. In the whole cohort, higher levels of PA were associated with significantly greater reductions in 10 senescence-related proteins at 12 and/or 24 months. These data reinforce cellular senescence as a contributing mechanism of age-associated functional decline and the potential for PA to attenuate this hallmark of aging. Clinical Trials Registration Number: NCT01072500.

Frontal adenosine triphosphate markers from 31P MRS are associated with cognitive performance in healthy older adults: preliminary findings.

Aging is associated with declines in mitochondrial efficiency and energy production which directly impacts the availability of adenosine triphosphate (ATP), which contains high energy phosphates critical for a variety of cellular functions. Previous phosphorous magnetic resonance spectroscopy (31P MRS) studies demonstrate cerebral ATP declines with age. The purpose of this study was to explore the functional relationships of frontal and posterior ATP levels with cognition in healthy aging. Here, we measured frontal and posterior ATP levels using 31P MRS at 3 Tesla (3 T) and assessed cognition using the Montreal Cognitive Assessment (MoCA) in 30 healthy older adults. We found that greater frontal, but not posterior, ATP levels were significantly associated with better MoCA performance. This relationship remained significant after controlling for age, sex, years of education, and brain atrophy. In conclusion, our findings indicate that cognition is related to ATP in the frontal cortex. These preliminary findings may have important implications in the search for non-invasive markers of in vivo mitochondrial function and the impact of ATP availability on cognition. Future studies are needed to confirm the functional significance of regional ATP and cognition across the lifespan.

Allostatic load and risk of all-cause, cancer-specific, and cardiovascular mortality in older cancer survivors: an analysis of the National Health and Nutrition Examination Survey 1999-2010.

Background: Allostatic load has been linked to an increased risk of death in various populations. However, to date, there is no research specifically investigating the effect of allostatic load on mortality in older cancer survivors. Aims: To investigate the association between allostatic load (AL) and mortality in older cancer survivors. Method: A total of 1,291 adults aged 60 years or older who survived for ≥1 year since cancer diagnoses were identified from the 1999-2010 National Health and Nutrition Examination Survey. AL was the exposure of interest incorporating 9 clinical measures/biomarkers; one point was added to AL if any of the measures/biomarkers exceeded the normal level. The sum of points was categorized as an ordinal variable to reflect low, moderate, and high AL. Our outcomes of interest were all-cause, cancer-specific, and cardiovascular disease (CVD)-specific mortality. Death was identified by linkage to the National Death Index. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence intervals (CI) of mortality by AL category. Results: Overall, 53.6% of participants were male and 78.4% were white. The mean age of study participants at interview was 72.8 years (SD=7.1). A total of 546 participants died during the follow-up (median follow-up time: 8.0 years). Among them, 158 died of cancer and 106 died of cardiovascular events. Results from multivariable Cox proportional hazards models showed that higher ALS was positively associated with higher all-cause mortality (ALS=4-9 vs. ALS =0-1: aHR=1.52, 95% CI =1.17-1.98, p-trend<0.01) and higher cancer-specific mortality (ALS=4-9 vs. ALS =0-1: aHR=1.80, 95% CI =1.12-2.90, p-trend=0.01). The association between ALS and cardiovascular mortality was positive but non-significant (ALS=4-9 vs. ALS =0-1: aHR=1.59, 95% CI =0.86-2.94, p-trend=0.11). Conclusions: Our study suggests that older cancer survivors can have a higher risk of death if they have a high burden of AL.

Study Design, Rationale, and Methodology for Promote Weight Loss in Patients With Peripheral Artery Disease Who Also Have Obesity: The PROVE Trial.

Background Overweight and obesity are associated with adverse functional outcomes in people with peripheral artery disease (PAD). The effects of weight loss in people with overweight/obesity and PAD are unknown. Methods The PROVE (Promote Weight Loss in Obese PAD Patients to Prevent Mobility Loss) Trial is a multicentered randomized clinical trial with the primary aim of testing whether a behavioral intervention designed to help participants with PAD lose weight and walk for exercise improves 6-minute walk distance at 12-month follow-up, compared with walking exercise alone. A total of 212 participants with PAD and body mass index ≥25 kg/m2 will be randomized. Interventions are delivered using a Group Mediated Cognitive Behavioral intervention model, a smartphone application, and individual telephone coaching. The primary outcome is 12-month change in 6-minute walk distance. Secondary outcomes include total minutes of walking exercise/wk at 12-month follow-up and 12-month change in accelerometer-measured physical activity, the Walking Impairment Questionnaire distance score, and the Patient-Reported Outcomes Measurement Information System mobility questionnaire. Tertiary outcomes include 12-month changes in perceived exertional effort at the end of the 6-minute walk, diet quality, and the Short Physical Performance Battery. Exploratory outcomes include changes in gastrocnemius muscle biopsy measures of mitochondrial cytochrome C oxidase activity, mitochondrial biogenesis, capillary density, and inflammatory markers. Conclusions The PROVE randomized clinical trial will evaluate the effects of exercise with an intervention of coaching and a smartphone application designed to achieve weight loss, compared with exercise alone, on walking performance in people with PAD and overweight/obesity. Results will inform optimal treatment for the growing number of patients with PAD who have overweight/obesity. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04228978.

Intraoperative Hemi-Diaphragm Electrical Stimulation Demonstrates Attenuated Mitochondrial Function without Change in Oxidative Stress in Cardiothoracic Surgery Patients.

Mechanical ventilation during cardiothoracic surgery is life-saving but can lead to ventilator-induced diaphragm dysfunction (VIDD) and prolong ventilator weaning and hospital length of stay. Intraoperative phrenic nerve stimulation may preserve diaphragm force production to offset VIDD; we also investigated changes in mitochondrial function after stimulation. During cardiothoracic surgeries (n = 21), supramaximal, unilateral phrenic nerve stimulation was performed every 30 min for 1 min. Diaphragm biopsies were collected after the last stimulation and analyzed for mitochondrial respiration in permeabilized fibers and protein expression and enzymatic activity of biomarkers of oxidative stress and mitophagy. Patients received, on average, 6.2 ± 1.9 stimulation bouts. Stimulated hemidiaphragms showed lower leak respiration, maximum electron transport system (ETS) capacities, oxidative phosphorylation (OXPHOS), and spare capacity compared with unstimulated sides. There were no significant differences between mitochondrial enzyme activities and oxidative stress and mitophagy protein expression levels. Intraoperative phrenic nerve electrical stimulation led to an acute decrease of mitochondrial respiration in the stimulated hemidiaphragm, without differences in biomarkers of mitophagy or oxidative stress. Future studies warrant investigating optimal stimulation doses and testing post-operative chronic stimulation effects on weaning from the ventilator and rehabilitation outcomes.

Transcriptomic and Proteomic of Gastrocnemius Muscle in Peripheral Artery Disease.

BACKGROUND: Few effective therapies exist to improve lower extremity muscle pathology and mobility loss due to peripheral artery disease (PAD), in part because mechanisms associated with functional impairment remain unclear. METHODS: To better understand mechanisms of muscle impairment in PAD, we performed in-depth transcriptomic and proteomic analyses on gastrocnemius muscle biopsies from 31 PAD participants (mean age, 69.9 years) and 29 age- and sex-matched non-PAD controls (mean age, 70.0 years) free of diabetes or limb-threatening ischemia. RESULTS: Transcriptomic and proteomic analyses suggested activation of hypoxia-compensatory mechanisms in PAD muscle, including inflammation, fibrosis, apoptosis, angiogenesis, unfolded protein response, and nerve and muscle repair. Stoichiometric proportions of mitochondrial respiratory proteins were aberrant in PAD compared to non-PAD, suggesting that respiratory proteins not in complete functional units are not removed by mitophagy, likely contributing to abnormal mitochondrial activity. Supporting this hypothesis, greater mitochondrial respiratory protein abundance was significantly associated with greater complex II and complex IV respiratory activity in non-PAD but not in PAD. Rate-limiting glycolytic enzymes, such as hexokinase and pyruvate kinase, were less abundant in muscle of people with PAD compared with non-PAD participants, suggesting diminished glucose metabolism. CONCLUSIONS: In PAD muscle, hypoxia induces accumulation of mitochondria respiratory proteins, reduced activity of rate-limiting glycolytic enzymes, and an enhanced integrated stress response that modulates protein translation. These mechanisms may serve as targets for disease modification.

The contribution of mitochondrial DNA alterations to aging, cancer, and neurodegeneration.

Mitochondrial DNA (mtDNA) is as a double-stranded molecule existing in hundreds to thousands copies in cells depending on cell metabolism and exposure to endogenous and/or environmental stressors. The coordination of mtDNA replication and transcription regulates the pace of mitochondrial biogenesis to guarantee the minimum number of organelles per cell. mtDNA inheritance follows a maternal lineage, although bi-parental inheritance has been reported in some species and in the case of mitochondrial diseases in humans. mtDNA mutations (e.g., point mutations, deletions, copy number variations) have been identified in the setting of several human diseases. For instance, sporadic and inherited rare disorders involving the nervous system as well higher risk of developing cancer and neurodegenerative conditions, including Parkinson's and Alzheimer's disease, have been associated with polymorphic mtDNA variants. An accrual of mtDNA mutations has also been identified in several tissues and organs, including heart and muscle, of old experimental animals and humans, which may contribute to the development of aging phenotypes. The role played by mtDNA homeostasis and mtDNA quality control pathways in human health is actively investigated for the possibility of developing targeted therapeutics for a wide range of conditions.

Mitochondrial Complex Abundance, Mitophagy Proteins, and Physical Performance in People With and Without Peripheral Artery Disease.

Background Mitochondrial abnormalities exist in gastrocnemius muscle of people with peripheral artery disease (PAD). Whether abnormalities in mitochondrial biogenesis and autophagy are associated with greater ischemia or walking impairment in PAD is unknown. Methods and Results Protein markers of mitochondrial biogenesis and autophagy and the abundance of mitochondrial electron transport chain complexes were quantified in gastrocnemius muscle biopsies from people with and without PAD. Their 6-minute walk distance and 4-m gait speed were measured. Sixty-seven participants (mean age 65.0 years [±6.8], 16 [23.9%] women, 48 [71.6%] Black) were enrolled, including 15 with moderate to severe PAD (ankle brachial index [ABI] <0.60), 29 with mild PAD (ABI 0.60-0.90), and 23 without PAD (ABI 1.00-1.40). Abundance of all electron transport chain complexes was significantly higher in participants with lower ABI (eg, complex I: 0.66, 0.45, 0.48 arbitrary units [AU], respectively, P trend=0.043). Lower ABI values were associated with a higher LC3A/B II-to-LC3A/B I (microtubule-associated protein 1A/1B-light chain 3) ratio (2.54, 2.31, 2.15 AU, respectively, P trend=0.017) and reduced abundance of the autophagy receptor p62 (0.71, 0.69, 0.80 AU, respectively, P trend=0.033). The abundance of each electron transport chain complex was positively and significantly associated with 6-minute walk distance and 4-m gait speed at usual and fast pace only among participants without PAD (eg, complex I: r=0.541, P=0.008; r=0.477, P=0.021; r=0.628, P=0.001, respectively). Conclusions These results suggest that accumulation of electron transport chain complexes in gastrocnemius muscle of people with PAD may be because of impaired mitophagy in the setting of ischemia. Findings are descriptive, and further study in larger sample sizes is needed.

Autophagy Meets Aging: An Overview.

Aging is characterized by biological disarrangements that increase vulnerability to stressors, the development of chronic diseases (e [...].

Relationship between Mitochondrial Quality Control Markers, Lower Extremity Tissue Composition, and Physical Performance in Physically Inactive Older Adults.

Altered mitochondrial quality and function in muscle may be involved in age-related physical function decline. The role played by the autophagy-lysosome system, a major component of mitochondrial quality control (MQC), is incompletely understood. This study was undertaken to obtain initial indications on the relationship between autophagy, mitophagy, and lysosomal markers in muscle and measures of physical performance and lower extremity tissue composition in young and older adults. Twenty-three participants were enrolled, nine young (mean age: 24.3 ± 4.3 years) and 14 older adults (mean age: 77.9 ± 6.3 years). Lower extremity tissue composition was quantified volumetrically by magnetic resonance imaging and a tissue composition index was calculated as the ratio between muscle and intermuscular adipose tissue volume. Physical performance in older participants was assessed via the Short Physical Performance Battery (SPPB). Protein levels of the autophagy marker p62, the mitophagy mediator BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), the lysosomal markers transcription factor EB, vacuolar-type ATPase, and lysosomal-associated membrane protein 1 were measured by Western immunoblotting in vastus lateralis muscle biopsies. Older adults had smaller muscle volume and lower tissue composition index than young participants. The protein content of p62 and BNIP3 was higher in older adults. A negative correlation was detected between p62 and BNIP3 and the tissue composition index. p62 and BNIP3 were also related to the performance on the 5-time sit-to-stand test of the SPPB. Our results suggest that an altered expression of markers of the autophagy/mitophagy-lysosomal system is related to deterioration of lower extremity tissue composition and muscle dysfunction. Additional studies are needed to clarify the role of defective MQC in human muscle aging and identify novel biological targets for drug development.

Cigarette smoking and mitochondrial dysfunction in peripheral artery disease.

BACKGROUND: This study evaluated the association of smoking with mitochondrial function in gastrocnemius muscle of people with peripheral artery disease (PAD). METHODS: Participants were enrolled from Chicago, Illinois and consented to gastrocnemius biopsy. Mitochondrial oxidative capacity was measured in muscle with respirometry. Abundance of voltage-dependent anion channel (VDAC) (mitochondrial membrane abundance), peroxisome proliferator-activated receptor-γ coactivator (PGC-1α) (mitochondrial biogenesis), and electron transport chain complexes I-V were measured with Western blot. RESULTS: Fourteen of 31 people with PAD (age 72.1 years, ABI 0.64) smoked cigarettes currently. Overall, there were no significant differences in mitochondrial oxidative capacity between PAD participants who currently smoked and those not currently smoking (complex I+II-mediated oxidative phosphorylation: 86.6 vs 78.3 pmolO2/s/mg, respectively [p = 0.39]). Among participants with PAD, those who currently smoked had a higher abundance of PGC-1α (p < 0.01), VDAC (p = 0.022), complex I (p = 0.021), and complex III (p = 0.021) proteins compared to those not currently smoking. People with PAD who currently smoked had lower oxidative capacity per VDAC unit (complex I+II-mediated oxidative phosphorylation [137.4 vs 231.8 arbitrary units, p = 0.030]) compared to people with PAD not currently smoking. Among people without PAD, there were no significant differences in any mitochondrial measures between currently smoking (n = 5) and those not currently smoking (n = 63). CONCLUSIONS: Among people with PAD, cigarette smoking may stimulate mitochondrial biogenesis to compensate for reduced oxidative capacity per unit of mitochondrial membrane, resulting in no difference in overall mitochondrial oxidative capacity according to current smoking status among people with PAD. However, these results were cross-sectional and a longitudinal study is needed.

Low muscle mass is associated with a higher risk of all-cause and cardiovascular disease-specific mortality in cancer survivors.

OBJECTIVES: Individuals with prior cancer diagnosis are more likely to have low muscle mass (LMM) than their cancer-free counterparts. Understanding the effects of LMM on the prognosis of cancer survivors can be clinically important. The aim of this study was to investigate whether risks for all-cause and cardiovascular disease (CVD)-specific mortality differ by status of LMM in cancer survivors and a matched cohort without cancer history. METHODS: We used cohort data from the 1999-2006 and 2011-2014 National Health and Nutrition Examination Survey. Participants included 946 adults surviving for ≥1 since cancer diagnosis and a matched cohort (by age, sex, and race) without cancer history (N = 1857). LMM was defined by appendicular lean mass and body height (men <7.26 kg/m2, women <5.45 kg/m2). Death was ascertained via the National Death Index and cause of death was assessed via International Classification of Diseases, Tenth Revision. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI) of LMM. RESULTS: The mean age of cancer survivors and matched cohort was 60.6 y (SD 15) and 60.2 y (SD 14.9), respectively. The median follow-up was 10.5 y for survivors and 10.9 y for matched cohort. Overall, 22.2% of cancer survivors and 19.7% of the matched cohort had LMM, respectively. In all, 321 survivors (33.9%) and 495 participants (26.7%) in the matched cohort died during follow-up. CVD-specific deaths were identified in 58 survivors (6.1%) and 122 participants in the matched cohort (6.6%). The multivariable Cox model suggested that LMM was positively associated with all-cause (aHR, 1.73; 95% CI, 1.31-2.29) and CVD-specific (aHR, 2.13; 95% CI, 1.14-4.00) mortality in cancer survivors. The associations between LMM and risk for all-cause (aHR, 1.24; 95% CI, 0.98-1.56) and CVD-specific (aHR, 1.21; 95% CI, 0.75-1.93) mortality were not statistically significant in the matched cohort. CONCLUSION: Cancer survivors with LMM have an increased risk for all-cause and CVD-specific mortality. This increase appears to be larger than that in counterparts without cancer history.