Publications

BACKGROUND: Approximately 35% of individuals over age 70 report difficulty with mobility. Muscle weakness has been demonstrated to be one contributor to mobility limitations in older adults. The purpose of this study was to examine the moderating effect of brain-predicted age difference (an index of biological brain age/health derived from structural neuroimaging) on the relationship between leg strength and mobility. METHODS: In community dwelling older adults (N = 57, 74.7 +/- 6.93 years; 68% women), we assessed the relationship between isokinetic leg extensor strength and a composite measure of mobility [mobility battery assessment (MBA)] using partial Pearson correlations and multifactorial regression modeling. Brain predicted age (BPA) was calculated from T1 MR-images using a validated machine learning Gaussian Process regression model to explore the moderating effect of BPA difference (BPAD; BPA minus chronological age). RESULTS: Leg strength was significantly correlated with BPAD (r = -0.317, p 0.05) and MBA score (r = 0.541, p 0.001). Chronological age, sex, leg strength, and BPAD explained 63% of the variance in MBA performance (p 0.001). BPAD was a significant moderator of the relationship between strength and MBA, accounting for 7.0% of MBA score variance [ big up tri, openR (2) = 0.044, F(1,51) = 6.83, p = 0.01]. Conditional moderation effects of BPAD indicate strength was a stronger predictor of mobility in those with a great BPAD. CONCLUSION: The relationship between strength and mobility appears to be influenced by brain aging, with strength serving as a possible compensation for decline in neural integrity.

BACKGROUND: Approximately 35% of individuals over age 70 report difficulty with mobility. Muscle weakness has been demonstrated to be one contributor to mobility limitations in older adults. The purpose of this study was to examine the moderating effect of brain-predicted age difference (an index of biological brain age/health derived from structural neuroimaging) on the relationship between leg strength and mobility. METHODS: In community dwelling older adults (N = 57, 74.7 +/- 6.93 years; 68% women), we assessed the relationship between isokinetic leg extensor strength and a composite measure of mobility [mobility battery assessment (MBA)] using partial Pearson correlations and multifactorial regression modeling. Brain predicted age (BPA) was calculated from T1 MR-images using a validated machine learning Gaussian Process regression model to explore the moderating effect of BPA difference (BPAD; BPA minus chronological age). RESULTS: Leg strength was significantly correlated with BPAD (r = -0.317, p 0.05) and MBA score (r = 0.541, p 0.001). Chronological age, sex, leg strength, and BPAD explained 63% of the variance in MBA performance (p 0.001). BPAD was a significant moderator of the relationship between strength and MBA, accounting for 7.0% of MBA score variance [ big up tri, openR (2) = 0.044, F(1,51) = 6.83, p = 0.01]. Conditional moderation effects of BPAD indicate strength was a stronger predictor of mobility in those with a great BPAD. CONCLUSION: The relationship between strength and mobility appears to be influenced by brain aging, with strength serving as a possible compensation for decline in neural integrity.

There is increasing interest in using motor function tests to identify risk of cognitive impairment in older adults (OA). This study examined associations among grip strength, with and without adjustment for muscle mass, manual dexterity and Trail Making Test (TMT) A and B in 77 OA (73.4 +/- 5.2 years) with globally intact cognition. A subset of OA who exhibited mismatched motor function (e.g., in the highest strength and lowest dexterity tertiles, or vice versa) was identified and analyzed. Dexterity showed stronger associations with TMT-A and -B than grip strength (absolute or adjusted). OA with mismatched motor function scored worse on tests of TMT-B, but not -A than those with matched motor function. Dexterity may have more promise than grip strength for identifying increased risk of cognitive impairment. Intriguing, though limited, data suggest that mismatched motor function (strength vs. dexterity) in OAs might be an even more robust marker of such risk.

BACKGROUND: Weakness is a common clinical symptom reported in individuals with chronic alcohol use disorder. However, it remains unclear whether low strength in these individuals is directly related to excessive ethanol intake, other deleterious factors (lifestyle, environment, genetics, etc.), or a combination of both. Therefore, we examined whether (and how) ethanol reduces the muscle's force-producing capacity using a controlled in vivo preclinical mouse model of excessive ethanol intake. METHODS: To establish whether chronic ethanol consumption causes weakness, C57BL/6 female mice consumed 20% ethanol for 40 weeks (following a 2-week ethanol ramping period), and various measures of muscular force were quantified. Functional measures included all-limb grip strength and in vivo contractility of the left ankle dorsiflexors and plantarflexors. Once confirmed that mice consuming ethanol were weaker than age-matched controls, we sought to determine the potential neuromuscular mechanisms of muscle dysfunction by assessing neuromuscular excitation, muscle quantity, and muscle quality. RESULTS: Mice consuming chronic ethanol were 13 to 16% weaker (p /= 0.268). No significant changes were observed between groups for indices of neuromuscular excitation at the level of the motor unit, neuromuscular junction, or plasmalemma (p >/= 0.259, n(2) /= 0.695, n(2)

BACKGROUND: Dietary fat quality is important for health and physical functioning in older adults. Linoleic acid is a dietary polyunsaturated fatty acid that is necessary for optimal inner-mitochondrial membrane function. However, limited evidence exists for examining the role of linoleic acid intake on indices of mobility and physical function. In this pilot study, we sought to examine the associations between linoleic acid intake and physical functioning in older adults. METHODS: This secondary analysis of data from the Health, Aging, and Body Composition energy expenditure sub-study was conducted for our investigation. Ability to complete physical tasks such as climbing a flight of stairs, walking a quarter mile, and lifting 10 lbs. was self-reported. Daily linoleic acid intake was estimated from a food frequency questionnaire. Persons with daily linoleic acid intake below approximately 85% of Adequate Intake were considered as having low linoleic acid intake. Covariate-adjusted logistic models were used for the analyses. RESULTS: The final analytical sample included 317 participants aged 74.4 +/- 2.8 years who consumed 18.9 +/- 11.4 g/day of linoleic acid, with 78 (24.6%) participants having low daily linoleic acid intake. Persons with low daily linoleic acid intake had 2.58 (95% confidence interval: 1.27-5.24) greater odds for a limitation in climbing stairs. CONCLUSIONS: Our pilot investigation found that low daily linoleic acid intake could be associated with physical function in older adults. Dietitians working with older patients may want to consider the importance of daily linoleic acid intake for health and certain physical function tasks.

Sarcopenia, or pathological loss of muscle mass and strength during aging, is an important contributor to loss of physical function in older adults. Sarcopenia is a multifactorial syndrome associated with intrinsic muscle and upstream neurological dysfunction. Exercise is well-established as an effective intervention for sarcopenia, but less is known about the long-term neurobiological impact of exercise. The goals of this study were to investigate the effects of exercise, alone or in combination with follistatin (FST) overexpression (antagonist of myostatin), on neuromuscular junction transmission and motor unit numbers in mice between the age of 22 and 27 months, ages at which prior studies have demonstrated that some motor unit loss is already evident. C57BL/6J mice underwent baseline assessment and were randomized to housing with or without voluntary running wheels and injection with adeno-associated virus to overexpress FST or vehicle. Groups for comparison included sedentary and running with and without FST. Longitudinal assessments showed significantly increased muscle mass and contractility in the 'running plus FST' group, but running, with and without FST, showed no effect on motor unit degeneration. In contrast, running, with and without FST, demonstrated marked improvement of neuromuscular junction transmission stability.

BACKGROUND: Serum zinc (Zn) levels have been shown to be associated with functional status; however, it is not clear whether this association differs by other sociodemographic characteristics. We examined the association between serum Zn levels and physical functioning difficulty in a representative sample of older adults in the US. DESIGN AND METHODS: A cross-sectional study was conducted on participants 50 years and older from the 2011-12 and 2013-14 National Health and Nutrition Examination Surveys (n = 1136). Serum Zn levels were analyzed as tertiles. The main outcome of interest was physical functioning difficulty, defined as self-reported difficulty of basic physical functioning that included walking, transferring, dressing, and feeding. RESULTS: Mean Zn levels (SE) were 0.67(0.1), 0.81(0.1), and 0.98(0.1) mug/mL in the low, middle, and high Zn groups, respectively. Approximately 24.9% participants reported physical functioning difficulty. In the multivariable model, we found a significant multiplicative interaction between sex and serum Zn (P for interaction =0.028) and between education and serum Zn (P for interaction = 0.001) on basic physical functioning difficulty. The stratified analysis revealed that among men, compared to those with low serum Zn, the odds of having physical functioning difficulty were lower in men who had high serum Zn [aOR 0.43 (95% CI: 0.25-0.76)]. For women, compared to those with low serum Zn the odds of having physical functioning difficulty were higher in women who had middle serum Zn [aOR 2.67 (1.58-4.50)]. Among individuals with less than high school education, the odds of having physical functioning difficulty were lower in those who had middle serum Zn compared to those who had low serum Zn [aOR 0.48 (0.26-0.89)]. However, the odds of having physical functioning difficulty were higher in those who had middle serum Zn compared to those who had low serum Zn for individuals with high school [aOR 5.72 (1.92-17.00)] and beyond high school education [aOR 1.77 (1.05-2.97)], respectively. CONCLUSION: Sex and educational attainment interact with serum Zn levels to influence basic physical functioning difficulty in older adults.