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Cardiorespiratory fitness and mitochondrial oxidative capacity are associated with reduced walking speed in older adults, but their impact on walking speed in older adults with diabetes has not been clearly defined. We examined differences in cardiorespiratory fitness and skeletal muscle mitochondrial oxidative capacity between older adults with and without diabetes, as well as determined their relative contribution to slower walking speed in older adults with diabetes. Participants with diabetes (n = 159) had lower cardiorespiratory fitness and mitochondrial respiration in permeabilized fiber bundles compared with those without diabetes (n = 717), following adjustments for covariates including BMI, chronic comorbid health conditions, and physical activity. Four-meter and 400-m walking speeds were slower in those with diabetes. Mitochondrial oxidative capacity alone or combined with cardiorespiratory fitness mediated ∼20-70% of the difference in walking speed between older adults with and without diabetes. Additional adjustments for BMI and comorbidities further explained the group differences in walking speed. Cardiorespiratory fitness and skeletal muscle mitochondrial oxidative capacity contribute to slower walking speeds in older adults with diabetes.

BACKGROUND: Phenotypic frailty syndrome identifies older adults at greater risk for adverse health outcomes. Despite the critical role of mitochondria in maintaining cellular function, including energy production, the associations between muscle mitochondrial energetics and frailty have not been widely explored in a large, well-phenotyped, older population. METHODS: The Study of Muscle, Mobility and Aging (SOMMA) assessed muscle energetics in older adults (N = 879, mean age = 76.3 years, 59.2% women). 31Phosporous magnetic resonance spectroscopy measured maximal production of adenosine triphosphate (ATPmax) in vivo, while ex vivo high-resolution respirometry of permeabilized muscle fibers from the vastus lateralis measured maximal oxygen consumption supported by fatty acids and complex I- and II-linked carbohydrates (e.g., Max OXPHOSCI+CII). Five frailty criteria, shrinking, weakness, exhaustion, slowness, and low activity, were used to classify participants as robust (0, N = 397), intermediate (1-2, N = 410), or frail (≥ 3, N = 66). We estimated the proportional odds ratio (POR) for greater frailty, adjusted for multiple potential confounders. RESULTS: One-SD decrements of most respirometry measures (e.g., Max OXPHOSCI+CII, adjusted POR = 1.5, 95%CI [1.2,1.8], p = 0.0001) were significantly associated with greater frailty classification. The associations of ATPmax with frailty were weaker than those between Max OXPHOSCI+CII and frailty. Muscle energetics was most strongly associated with slowness and low physical activity components. CONCLUSIONS: Our data suggest that deficits in muscle mitochondrial energetics may be a biological driver of frailty in older adults. On the other hand, we did observe differential relationships between measures of muscle mitochondrial energetics and the individual components of frailty.

Social stress experienced in childhood is associated with adverse health later in life. Mitochondrial function has been implicated as a mechanism for how stressful life events get under the skin to influence physical well-being. Using data from the Study of Muscle, Mobility, and Aging (n = 879, 59% women), linear models examined whether adverse childhood events (i.e., physical abuse) were associated with two measures of skeletal muscle mitochondrial energetics in older adults: (i) maximal adenosine triphosphate production (ATPmax) and (ii) maximal state 3 respiration (Max OXPHOS). Forty-five percent of the sample reported experiencing one or more adverse childhood events. After adjustment, each additional event was associated with -0.08 SD (95% confidence interval = -0.13, -0.02) lower ATPmax. No association was observed with Max OXPHOS. Adverse childhood events are associated with lower ATP production in later life. Findings indicate that mitochondrial function may be a mechanism for understanding how early social stress influences health in later life.

BackgroundFalls in the older population are a major public health concern. While many physiological and environmental factors have been associated with fall risk, muscle mitochondrial energetics has not yet been investigated.MethodsIn this analysis, 835 Study of Muscle, Mobility and Aging (SOMMA) participants aged 70-94 were surveyed for number of falls (total), recurrent falls (2+), and fall-related injuries over the past 12 months at baseline and again after one year. Skeletal muscle energetics were assessed at baseline in vivo using 31P Magnetic Resonance Spectroscopy (MRS) after an acute bout of exercise (ATPmax) and ex vivo by High Resolution Respirometry (HRR) of permeabilized muscle fibers from the vastus lateralis (MaxOXPHOS).ResultsAt least one fall was reported in 28.7% of SOMMA participants in the first year of the study, with 12% of older adults reporting recurrent falls (2+). Individuals who experienced recurrent falls had a slower 400m walk gait speed (1.0 ± 0.2 vs. 1.1 ± 0.2, p

Oxidative stress is considered a contributor to declining muscle function and mobility during aging; however, the underlying molecular mechanisms remain poorly described. We hypothesized that greater levels of cysteine (Cys) oxidation on muscle proteins are associated with decreased measures of mobility. Herein, we applied a novel redox proteomics approach to measure reversible protein Cys oxidation in vastus lateralis muscle biopsies collected from 56 subjects in the Study of Muscle, Mobility and Aging (SOMMA), a community‐based cohort study of individuals aged 70 years and older. We tested whether levels of Cys oxidation on key muscle proteins involved in muscle structure and contraction were associated with muscle function (leg power and strength), walking speed, and fitness (VO2 peak on cardiopulmonary exercise testing) using linear regression models adjusted for age, sex, and body weight. Higher oxidation levels of select nebulin Cys sites were associated with lower VO2 peak, while greater oxidation of myomesin‐1, myomesin‐2, and nebulin Cys sites was associated with slower walking speed. Higher oxidation of Cys sites in key proteins such as myomesin‐2, alpha‐actinin‐2, and skeletal muscle alpha‐actin were associated with lower leg power and strength. We also observed an unexpected correlation (R = 0.48) between a higher oxidation level of eight Cys sites in alpha‐actinin‐3 and stronger leg power. Despite this observation, the results generally support the hypothesis that Cys oxidation of muscle proteins impairs muscle power and strength, walking speed, and cardiopulmonary fitness with aging. [ABSTRACT FROM AUTHOR]

The age-related decline in muscle mitochondrial energetics contributes to the loss of mobility in older adults. Women experience a higher prevalence of mobility impairment compared to men, but it is unknown whether sex-specific differences in muscle energetics underlie this disparity. In the Study of Muscle, Mobility and Aging (SOMMA), muscle energetics were characterized using in vivo phosphorus-31 magnetic resonance spectroscopy and high-resolution respirometry of vastus lateralis biopsies in 773 participants (56.4% women, age 70–94 years). A Short Physical Performance Battery (SPPB) score ≤8 was used to define lower-extremity mobility impairment. Muscle mitochondrial energetics were lower in women compared to men (eg, Maximal Complex I&II OXPHOS: Women = 55.06 ± 15.95; Men = 65.80 ± 19.74; p  < .001) and in individuals with mobility impairment compared to those without (eg, Maximal Complex I&II OXPHOS in women: SPPB ≥ 9 = 56.59 ± 16.22; SPPB ≤ 8 = 47.37 ± 11.85; p  < .001). Muscle energetics were negatively associated with age only in men (eg, Maximal ETS capacity: R  = −0.15, p  = .02; age/sex interaction, p  = .04), resulting in muscle energetics measures that were significantly lower in women than men in the 70–79 age group but not the 80+ age group. Similarly, the odds of mobility impairment were greater in women than men only in the 70–79 age group (70–79 age group, odds ratio [OR]age-adjusted = 1.78, 95% confidence interval [CI] = 1.03, 3.08, p  = .038; 80+ age group, ORage-adjusted = 1.05, 95% CI = 0.52, 2.15, p  = .89). Accounting for muscle energetics attenuated up to 75% of the greater odds of mobility impairment in women. Women had lower muscle mitochondrial energetics compared to men, which largely explain their greater odds of lower-extremity mobility impairment. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial energetics are an important property of aging muscle, as generation of energy is pivotal to the execution of muscle contraction. However, its association with functional outcomes, including leg power and cardiorespiratory fitness is largely understudied.Methods: In the Study of Muscle, Mobility, and Aging (SOMMA), we collected vastus lateralis biopsies from older adults (n=879,70-94 years,59.2% women). Maximal state 3 respiration (Max OXPHOS) was assessed in permeabilized fiber bundles by high-resolution respirometry. Capacity for maximal adenosine triphosphate production (ATPmax) was measured in vivo by 31P magnetic resonance spectroscopy. Leg extension power was measured with a Keiser press system, and VO2 peak was determined using a standardized cardiopulmonary exercise test. Gender-stratified multivariate linear regression models were adjusted for age, race, technician/site, adiposity, and physical activity with beta-coefficients expressed per 1 SD increment in the independent variable.Results: Max OXPHOS was associated with leg power for both women (β=0.12Watts/kg,p<0.001) and men (β=0.11Watts/kg,p<0.050). ATPmax was associated with leg power for men (β=0.09Watts/kg p<0.05) but was not significant for women (β=0.03Watts/kg,p=0.11). Max OXPHOS and ATPmax were associated with VO2 peak in women and men (Max OXPHOS, βwomen=1.03mL/kg/min, βmen=1.32 mL/kg/min; ATPmax βwomen=0.87mL/kg/min, βmen=1.50mL/kg/min;all p<0.001).Conclusions: Higher muscle mitochondrial energetics measures were associated with both better cardiorespiratory fitness and greater leg power in older adults. Muscle mitochondrial energetics explained a greater degree of variance in VO2 peak compared to leg power. [ABSTRACT FROM AUTHOR]

This study examines how a state system of higher education, located in the Rocky Mountains area of the United States, allowed faculty members from the state's public institutions of higher education to control the design and implementation of a pilot assessment of statewide general education courses. One of the primary reasons faculty were allowed to control the assessment process was to assuage the commonly held fear by faculty, academic departments, and institutions that they could be punished for the poor assessment results of their students who took the pilot assessment. An important conclusion of this study is that the promise of anonymity, given by the state board of regents (and tacitly by the legislature) to individual faculty members, academic departments, and institutions, was essential to the success of the assessment process. (Contains 2 notes.)

People who become educational leadership professors usually come to their new occupation with a range of skills and experiences. Most doctoral preparation programs in educational leadership however do not always prepare future faculty members to address conflicts that arise when the actual roles and responsibilities of the new faculty member conflict with either their own norms and values or the institutions' norms, values, or mission. This case is an opportunity to consider how new faculty prepare for entrance into the professoriate. This case guides the reader through an exploration of faculty expectations of their students and themselves and how to plan student evaluations given students' characteristics in the context and the culture of the institution. Future faculty members can benefit from a thoughtful consideration of themselves and how their expectations for themselves and their students affect the teaching and learning process.

Introduction: Despite evidence for systemic mitochondrial dysfunction early in Alzheimer's disease (AD) pathogenesis, reliable approaches monitoring these key bioenergetic alterations are lacking. We used peripheral blood mononuclear cells (PBMCs) and platelets as reporters of mitochondrial function in the context of cognitive impairment and AD. Methods: Mitochondrial function was analyzed using complementary respirometric approaches in intact and permeabilized cells from older adults with normal cognition, mild cognitive impairment (MCI), and dementia due to probable AD. Clinical outcomes included measures of cognitive function and brain morphology. Results: PBMC and platelet bioenergetic parameters were lowest in dementia participants. MCI platelets exhibited higher maximal respiration than normocognitives. PBMC and platelet respiration positively associated with cognitive ability and hippocampal volume, and negatively associated with white matter hyperintensities. Discussion: Our findings indicate blood‐based bioenergetic profiling can be used as a minimally invasive approach for measuring systemic bioenergetic differences associated with dementia, and may be used to monitor bioenergetic changes associated with AD risk and progression. Highlights: Peripheral cell bioenergetic alterations accompanied cognitive decline in older adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD) and related dementia (DEM).Peripheral blood mononuclear cells (PBMC) and platelet glucose‐mediated respiration decreased in participants with dementia compared to normocognitive controls (NC).PBMC fatty‐acid oxidation (FAO)‐mediated respiration progressively declined in MCI and AD compared to NC participants, while platelet FAO‐mediated respiration exhibited an inverse‐Warburg effect in MCI compared to NC participants.Positive associations were observed between bioenergetics and Modified Preclinical Alzheimer's Cognitive Composite, and bioenergetics and hippocampal volume %, while a negative association was observed between bioenergetics and white matter hyperintensities.Systemic mitochondrial dysfunction is associated with cognitive decline. [ABSTRACT FROM AUTHOR]

Many college faculty react to student outcomes assessment the way most people react when they see a rattlesnake within striking distance. Common faculty reactions to the perceived threat of assessment include metaphorically running away and throwing rocks or sticks at it. Like a hiker in the desert doing her best to avoid being struck when she encounters a rattlesnake, a number of faculty members react to assessment activities by doing what they can to avoid or resist them. In this article, the author suggests that one way to address faculty avoidance or resistance is to create an antidote. In a way similar to how anti-venom is created for venomous bites or stings--that is, by receiving small doses of assessment over time--faculty may be able to build up their assessment immunity. Put another way, when assessment work is introduced to faculty in a way that is both collegial and collaborative, and when it is given in small, manageable doses while emphasizing the positive aspects of assessment, faculty resistance may be reduced significantly.