Safety and tolerability of chronic intranasal oxytocin in older men: results from a randomized controlled trial.

RATIONALE: Most studies evaluating the safety and tolerability of intranasal oxytocin (OT) have not reported consistent adverse events (AEs), but they have largely focused on young men and single-dose administration. Thus, it is unclear whether these findings translate to older individuals and with longer administration periods. OBJECTIVE: Extending previous work, this study investigated the safety and tolerability of chronic intranasal OT in generally healthy older men. METHODS: Data were from a randomized, placebo (P)-controlled, double-blind clinical trial evaluating the effects of 4 weeks of self-administered intranasal OT (24 IU twice daily) in older adults with no major physical or cognitive impairments. Heart rate, blood pressure, urine osmolality, and serum metabolic biomarkers were obtained before and at the end of the intervention. AEs were collected during the first 3 weeks and 1 week after cessation of treatment. RESULTS: Of 103 participants recruited, 95 were randomized and received the intervention (OT = 49, P = 46). OT had no significant impact on cardiovascular, urine, or serum measures. The AEs reported for both treatments were generally mild and few in number, though one participant assigned to OT and two assigned to P dropped out due to AEs. Relative to P, OT did not significantly increase the likelihood of reporting AEs, nor the number or severity of AEs reported. CONCLUSION: Chronic intranasal OT appears safe and well-tolerated in generally healthy older men. These findings provide support for continued human research on potential benefits of chronic OT in older adult populations.

Wearable Technology To Reduce Sedentary Behavior And CVD Risk In Older Adults: A Pilot Randomized Clinical Trial.

BACKGROUND: Physical exercise is associated with decreased cardiovascular disease (CVD) risk, but recent large-scale trials suggest that exercise alone is insufficient to reduce CVD events in high-risk older adults. PURPOSE: This pilot randomized clinical trial aimed to collect critical data on feasibility, safety, and protocol integrity necessary to design a fully powered randomized controlled trial (RCT) and evaluate the impact of combining structured exercise with an intervention designed to enhance non-exercise physical activity (EX+NEPA) compared to EX alone. METHODS: Forty participants aged ≥60 years with moderate-to-high risk of coronary heart disease events were randomly assigned to either the EX+NEPA or EX groups and followed for 20 weeks. Both groups underwent a twice-weekly, 8-week center-based exercise intervention with aerobic and resistance exercises. EX+NEPA group also received a wearable activity tracking device along with behavioral monitoring and feedback throughout the study. Study outcomes were evaluated at 8 and 20 weeks. RESULTS: Data are presented as adjusted mean change of the differences over time with 95% confidence intervals at 20 weeks. Relative to EX, the change in steps/day at 20 weeks was 1994 (-40.27, 4028) higher for EX+NEPA. For sedentary time at close-out, the EX+NEPA group was -6.8 (-45.2, 31.6) min/day relative to EX. The between-group differences for systolic and diastolic blood pressure were -9.9 (-19.6, -0.3) and -1.8 (-6.9, 3.3) mmHg, respectively. CONCLUSION: The addition of wearable technology intervention appeared to positively influence daily activity patterns and changes in blood pressure - potentially improving risk factors for CVD. A fully powered randomized trial is needed to ultimately test this hypothesis.

Multimodal Intervention to Improve Functional Status in Hypertensive Older Adults: A Pilot Randomized Controlled Trial.

This pilot randomized controlled trial (RCT) was designed to provide the preliminary data necessary to conduct a full-scale trial to compare the efficacy of differing first-line antihypertensive medications in improving functional status in older adults, when combined with exercise. The primary objectives were to assess study feasibility, safety, and protocol integrity. Dependent outcomes included gait speed, exercise capacity, body composition, and systemic cardiometabolic biomarkers. Thirty-one physically inactive older adults (70.6 ± 6.1 years) with hypertension and functional limitations were randomly assigned to 1) Perindopril (8 mg/day n = 10), 2) Losartan (100 mg/day; n = 13), or 3) Hydrochlorothiazide (HCTZ: 25 mg/day; n = 8). Participants were also assigned to a 24-week multimodal exercise intervention, separated into an aerobic and concurrent (aerobic + resistance) phase to evaluate potential mode effects. Retention was 84% (26/31), and compliance was >90% and >79% with medication and exercise, respectively. A total of 29 adverse events (Perindopril = 5; Losartan = 12; HCTZ = 11) and one unrelated serious adverse event were observed throughout the trial. Overall, this pilot RCT provided critical data and identified several challenges to ultimately designing and implementing a fully powered trial.

Resveratrol and exercise to treat functional limitations in late life: design of a randomized controlled trial.

Skeletal muscle mitochondrial function declines with age and is a key factor in the maintenance of physical function among older adults. Research studies from animals and humans have consistently demonstrated that exercise improves skeletal muscle mitochondrial function in early and middle adulthood. However, mitochondrial adaptations to both acute and chronic exercise are attenuated in late life. Thus, there is an important need to identify adjuvant therapies capable of augmenting mitochondrial adaptations to exercise (e.g. improved mitochondrial respiration, muscle mitochondria biogenesis) among older adults. This study is investigating the potential of resveratrol supplementation for this purpose. The objective of this randomized, double-masked pilot trial is to evaluate the efficacy of resveratrol supplementation combined with a comprehensive supervised exercise program exercise for improving physical function among older adults. Moderately functioning, sedentary participants aged ≥60 years will perform 24 sessions (2 day/wk for 12 weeks) of center-based walking and resistance training and are randomly assigned to receive either (1) 500 mg/day resveratrol (2) 1000 mg/day resveratrol or (3) placebo. Study dependent outcomes include changes in 1) knee extensor strength, 2) objective measures of physical function (e.g. 4m walk test, Short Physical Performance Battery), 3) subjective measures of physical function assessed by Late Life Function and Disability Instrument, and 4) skeletal muscle mitochondrial function. This study will provide novel information regarding the therapeutic potential of resveratrol supplementation combined with exercise while also informing about the long-term clinical viability of the intervention by evaluating participant safety and willingness to engage in the intervention.

Wearable technology to reduce sedentary behavior and CVD risk in older adults: design of a randomized controlled trial.

Persons aged over 65 years account for over the vast majority of healthcare expenditures and deaths attributable to cardiovascular disease (CVD). Accordingly, reducing CVD risk among older adults is an important public health priority. Structured physical activity (i.e. exercise) is a well-documented method of decreasing CVD risk, but recent large-scale trials suggest that exercise alone is insufficient to reduce CVD events in high-risk populations of older adults. Thus adjuvant strategies appear necessary to reduce CVD risk. Accumulating evidence indicates that prolonged sedentary behavior (e.g. sitting) has detrimental health effects that are independent of engagement in recommended levels of moderate-intensity exercise. Yet clinical trials in this area are lacking. We hypothesize that exercise, when combined with a novel technology based intervention specifically designed to reduce sedentary behavior will reduce CVD risk among sedentary older adults. The purpose of this study is to evaluate the feasibility and efficacy of combining a traditional, structured exercise intervention with an innovative intervention designed to decrease sedentary behavior and increase non-exercise physical activity (NEPA). This study will provide us with critical data necessary to design and implement a full-scale trial to test our central hypothesis. Participants aged ≥60 years with moderate to high risk of coronary heart disease (CHD) events are randomly assigned to either the exercise and technology intervention (EX+NEPA) or exercise alone (EX) groups. Study dependent outcomes include changes in 1) daily activity patterns, 2) blood pressure, 3) exercise capacity, 4) waist circumference, and 5) circulating indices of cardiovascular function. This study will provide critical information for designing a fully-powered clinical trial, which could have health implications for the ever increasing population of older adults.

Effects of blood-flow restriction on biomarkers of myogenesis in response to resistance exercise.

We investigated the acute myogenic response to resistance exercise with and without blood-flow restriction (BFR). Six men and women (age, 22 ± 1 years) performed unilateral knee extensions at 40% of 1-repetition maximum with or without (CNTRL) BFR applied via pressure cuff inflated to 220 mm Hg. Muscle biopsies were collected at 4 h and 24 h postexercise. Addition of BFR increased myoD and c-Met messenger RNA expression relative to CNTRL. Expression of hepatocyte growth factor protein was significantly higher following CNTRL.

Idiopathic chronic fatigue in older adults is linked to impaired mitochondrial content and biogenesis signaling in skeletal muscle.

Fatigue is a symptom of many diseases, but it can also manifest as a unique medical condition, such as idiopathic chronic fatigue (ICF). While the prevalence of ICF increases with age, mitochondrial content and function decline with age, which may contribute to ICF. The purpose of this study was to determine whether skeletal muscle mitochondrial dysregulation and oxidative stress is linked to ICF in older adults. Sedentary, old adults (n = 48, age 72.4 ± 5.3 years) were categorized into ICF and non-fatigued (NF) groups based on the FACIT-Fatigue questionnaire. ICF individuals had a FACIT score one standard deviation below the mean for non-anemic adults > 65 years and were excluded according to CDC diagnostic criteria for ICF. Vastus lateralis muscle biopsies were analyzed, showing reductions in mitochondrial content and suppression of mitochondrial regulatory proteins Sirt3, PGC-1α, NRF-1, and cytochrome c in ICF compared to NF. Additionally, mitochondrial morphology proteins, antioxidant enzymes, and lipid peroxidation were unchanged in ICF individuals. Our data suggests older adults with ICF have reduced skeletal muscle mitochondrial content and biogenesis signaling that cannot be accounted for by increased oxidative damage.

Successful aging: Advancing the science of physical independence in older adults.

The concept of 'successful aging' has long intrigued the scientific community. Despite this long-standing interest, a consensus definition has proven to be a difficult task, due to the inherent challenge involved in defining such a complex, multi-dimensional phenomenon. The lack of a clear set of defining characteristics for the construct of successful aging has made comparison of findings across studies difficult and has limited advances in aging research. A consensus on markers of successful aging is furthest developed is the domain of physical functioning. For example, walking speed appears to be an excellent surrogate marker of overall health and predicts the maintenance of physical independence, a cornerstone of successful aging. The purpose of the present article is to provide an overview and discussion of specific health conditions, behavioral factors, and biological mechanisms that mark declining mobility and physical function and promising interventions to counter these effects. With life expectancy continuing to increase in the United States and developed countries throughout the world, there is an increasing public health focus on the maintenance of physical independence among all older adults.

Active muscle regeneration following eccentric contraction-induced injury is similar between healthy young and older adults.

Repair of skeletal muscle after injury is a key aspect of maintaining proper musculoskeletal function. Studies have suggested that regenerative processes, including myogenesis and angiogenesis, are impaired during advanced age, but evidence from humans is limited. This study aimed to compare active muscle regeneration between healthy young and older adults. We evaluated changes in clinical, biochemical, and immunohistochemical indices of muscle regeneration at precisely 2 (T2) and 7 (T3) days following acute muscle injury. Men and women, aged 18-30 and ≥70 years, matched for gender and body mass index, performed 150 unilateral, eccentric contractions of the plantar flexors at 110% of one repetition maximum. Data were analyzed using analysis of covariance, adjusted for gender, habitual physical activity, and baseline level of the outcome. A total of 30 young (n = 15; 22.5 ± 3.7 yr) and older (n = 15; 75.8 ± 5.0 yr) adults completed the study. Following muscle injury, force production declined 16% and 14% in young and older adults, respectively, by T2 and in each group, returned to 93% of baseline strength by T3. Despite modest differences in the pattern of response, postinjury changes in intramuscular concentrations of myogenic growth factors and number of myonuclear (4',6-diamidino-2-phenylindole+ and paired box 7+) cells were largely similar between groups. Likewise, postinjury changes in serum and intramuscular indices of inflammation (e.g., TNF-α and monocyte chemoattractant protein-1) and angiogenesis (e.g., VEGF and kinase insert domain receptor) did not differ significantly between groups. These findings suggest that declines in physical activity and increased co-morbidity may contribute to age-related impairments in active muscle regeneration rather than aging per se.