Citations

Autophagy is a process through which damaged cytoplasmic structures are recycled and degraded within the cell. Aging can affect autophagy regulation in different steps and lead to the accumulation of altered proteins, leading to cell damage and death. Motor neuron (MN) loss is an important contributor to sarcopenia age-dependent motor dysfunction. Understanding the regulatory mechanisms of autophagy can help elucidate the motor dysfunction that occurs with aging and provide a target for developing future therapeutic agents. Previous immunofluorescence imaging studies in phrenic MNs showed an age-dependent increase in key autophagy proteins LC3 and p62, reflecting autophagosome accumulation and autophagy impairment. Accordingly, we hypothesized that aging in lumbar MNs leads to autophagy impairment reflected in regulatory protein expression. The current study assessed autophagy in choline acetyltransferase-positive MNs from spinal levels L1-L6, focused on crural muscles (extensor digitorum longus and soleus), using confocal immunofluorescence imaging. Expression of LC3 and p62 proteins in MNs were determined in male and female C57BL/6 mice at 6-, 18- and 24- months of age. Increased expression of LC3 in lumbar MNs was observed with aging across all three age groups and p62 expression in lumbar MNs was significantly increased by 24- and 18-months compared to 6-months (p<0.001). There was no sex effect observed in LC3, but p62 was significantly higher in lumbar MNs of female mice (p=0.007). Expression of both LC3 and p62 increased diffusely in ventral lumbar gray matter regions with age (p<0.001), an effect that was predominant in male and not female mice. Taken together, the results of this study provide evidence for that age-dependent changes in autophagy markers expression occurs in regions of the spinal cord (motor neurons and ventral horn gray matter). The neuronal mechanisms of aging effects include dysregulation of autophagy. Supported by NIH R01 AG057052. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract Women with premenopausal bilateral oophorectomy (PBO) are at increased risk for physical function (PF) declines. This study investigated the relationships of field-based physical activity measures with clinical PF and strength parameters in post-menopausal women with and without PBO. Women with (n=21; age=64±4 years; BMI=32±8 kg.m-2) and without (n=15; age=67±6 years; BMI=28±6 kg.m-2) PBO performed PF and strength tests (walking speed, distance walked, short physical performance battery (SPBB), leg and chest strength), and wore ankle accelerometers for 7 days (daily step count and loading index [the cumulative sum of each step’s skeletal loading]). Age, BMI, step count and loading index were entered into stepwise multiple regression to identify significant predictors of PF and strength parameters. Step count was a predictor of SPBB score in both groups. In women without PBO, step count was a predictor of walking speed; loading index was a predictor of leg strength; step count and loading index were predictors of distance; and step count and age were predictors of chest strength. For PBO women, loading index and BMI were predictors of walking speed and distance; BMI was a predictor of leg strength; and there were no predictors of chest strength. These data suggest while field-based physical activity was strongly and positively associated with clinical PF and strength measures for women without PBO, BMI was a dominant negative factor for PF in women with PBO. Future work will include a larger sample size and additional confounders to further elucidate underlying factors of reduced PF and mobility after PBO.

Background: Individuals with spinal cord injury (SCI) who use manual wheelchairs (MWCs) have a higher rate of rotator cuff pathology progression than able-bodied individuals. Objectives: This study aimed to test the ability of risk and recovery metrics of arm use to differentiate between (1) MWC users with SCI and matched able-bodied participants (cross-sectional matched-sample study) and (2) MWC users with rotator cuff pathology progression over 1 year from those without pathology progression (longitudinal study). Methods: Thirty-four MWC users and 34 age- and sex-matched able-bodied individuals were recruited. Upper arm risk (humeral elevation >60°) and recovery (static ≥5 seconds and humeral elevation <40°) metrics were calculated from wireless inertial measurement units (IMUs) worn on the upper arms and torso in the free-living environment. Two separate magnetic resonance imaging studies were completed and assessed for a subset of 16 MWC users approximately 1 year apart. Results: The frequency of risk events ( p = .019), summated duration of recovery events ( p = .025), and duration of each recovery event ( p = .003) were higher for MWC users than able-bodied participants. The summated duration of risk events ( p = .047), frequency of risk events ( p = .027), and risk to recovery ratio ( p = .02) were higher and the summated duration of recovery events ( p = .036) and frequency of recovery events ( p = .047) were lower for MWC users with rotator cuff pathology progression ( n = 5) compared to those without progression ( n = 11). Conclusion: IMU-derived metrics quantifying arm use at postures >60° and risk to recovery ratios may provide insights of potential risk factors for rotator cuff pathology progression.

Arm use in manual wheelchair (MWC) users is characterized by a combination of overuse and a sedentary lifestyle. This study aimed to describe the percentage of daily time MWC users and able-bodied individuals spend in each arm use intensity level utilizing accelerometers. Arm use intensity levels of the upper arms were defined as stationary, low, mid, and high from the signal magnitude area (SMA) of the segment accelerations based on in-lab MWC activities performed by eight MWC users. Accelerometry data were collected in the free-living environments from forty MWC users and 40 sex- and age-matched able-bodied individuals. The SMA intensity levels were applied to the free-living data and the percentage of time spent in each level was calculated. The SMA intensity levels were defined as, stationary: ≤0.67 g, low: 0.671–3.27 g, mid: 3.27–5.87 g, and high: >5.871 g. The dominant arm of both MWC users and able-bodied individuals was stationary for most of the day and less than one percent of the day was spent in high intensity arm activities. Increased MWC user age correlated with increased stationary arm time (R = 0.368, p = 0.019). Five and eight days of data are needed from MWC users and able-bodied individuals, respectively, to achieve reliable representation of their daily arm use intensities.