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Chronic, low-grade inflammation increases with aging, contributing to functional declines and diseases that reduce healthspan. Growing evidence suggests that transcripts from repetitive elements (RE) in the genome contribute to this "inflammaging" by stimulating innate immune activation, but evidence of RE-associated inflammation with aging in humans is limited. Here, we present transcriptomic and clinical data showing that RE transcript levels are positively related to gene expression of innate immune sensors, and to serum interleukin 6 (a marker of systemic inflammation), in a large group of middle-aged and older adults. We also: (1) use transcriptomics and whole-genome bisulfite (methylation) sequencing to show that many RE may be hypomethylated with aging, and that aerobic exercise, a healthspan-extending intervention, reduces RE transcript levels and increases RE methylation in older adults; and (2) extend our findings in a secondary dataset demonstrating age-related changes in RE chromatin accessibility. Collectively, our data support the idea that age-related RE transcript accumulation may play a role in inflammaging in humans, and that RE dysregulation with aging may be due in part to upstream epigenetic changes. [ABSTRACT FROM AUTHOR]

Introduction: Cannabis, commonly known for both therapeutic and intoxicating effects, is gaining accessibility on legal markets and traction as a potential alternative therapy for pain mediation, particularly in those suffering from chronic low back pain. However, the effectiveness in this population of legal market forms of cannabis, particularly commonly used edibles, is unknown. Methods: Therefore, this study utilized a naturalistic prospective design where participants with chronic low back pain with intentions to initiate cannabis use for treatment were recruited and self-selected edible cannabis products containing varying amounts of delta- 9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Products were categorized as CBD-dominant, THC-dominant, or combined THC and CBD (THC + CBD). Results: 249 participants [140 female (56.62%), mean (SD) age of 46.30 (16.02), 90% White] were tracked over 2 weeks of ad libitum use and assessed during a naturalistic acute cannabis administration session on changes in pain, mood, and subjective drug effects. During acute administration, a significant correlation between THC dose and short-term pain relief was found, suggesting that higher THC doses were associated with greater pain reduction (p <.05). In addition, THC was associated with higher levels of subjective cannabis drug effects (p <.001), regardless of whether CBD was also in the edible product. Acute CBD dose was primarily associated with short-term tension relief (p <.05); however, there were no associations between CBD dose and acute pain. Over the 2-week ad libitum administration period results suggested pain reductions across participants using all forms of cannabis. However, trends suggested that more frequent use of CBD-dominant edible cannabis may be associated with greater reductions in perceived pain over the 2-week observation period (p =.07). Discussion: These findings support the short-term analgesic effects of THC and anxiolytic effects of CBD and further suggest that orally-administered THC and CBD should continue to be evaluated for the potential to provide both acute and extended relief from chronic low back pain. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT03522324?locStr=Boulder,%20CO&country=United%20States&state=Colorado&city=Boulder&cond=chronic%20low%20back%20pain&intr=Cannabis&rank=1, identifier NCT03522324. [ABSTRACT FROM AUTHOR]

Introduction: Cannabis, commonly known for both therapeutic and intoxicating effects, is gaining accessibility on legal markets and traction as a potential alternative therapy for pain mediation, particularly in those suffering from chronic low back pain. However, the effectiveness in this population of legal market forms of cannabis, particularly commonly used edibles, is unknown. Methods: Therefore, this study utilized a naturalistic prospective design where participants with chronic low back pain with intentions to initiate cannabis use for treatment were recruited and self-selected edible cannabis products containing varying amounts of delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Products were categorized as CBD-dominant, THC-dominant, or combined THC and CBD (THC + CBD). Results: 249 participants [140 female (56.62%), mean (SD) age of 46.30 (16.02), 90% White] were tracked over 2 weeks of ad libitum use and assessed during a naturalistic acute cannabis administration session on changes in pain, mood, and subjective drug effects. During acute administration, a significant correlation between THC dose and short-term pain relief was found, suggesting that higher THC doses were associated with greater pain reduction (p < .05). In addition, THC was associated with higher levels of subjective cannabis drug effects (p < .001), regardless of whether CBD was also in the edible product. Acute CBD dose was primarily associated with short-term tension relief (p < .05); however, there were no associations between CBD dose and acute pain. Over the 2-week ad libitum administration period results suggested pain reductions across participants using all forms of cannabis. However, trends suggested that more frequent use of CBDdominant edible cannabis may be associated with greater reductions in perceived pain over the 2-week observation period (p = .07). Discussion: These findings support the short-term analgesic effects of THC and anxiolytic effects of CBD and further suggest that orally-administered THC and CBD should continue to be evaluated for the potential to provide both acute and extended relief from chronic low back pain. [ABSTRACT FROM AUTHOR]

Background: As cannabis legalization continues to spread across the United States, average Δ9-tetrahydrocannabinol concentrations in recreational products have significantly increased, and no prior study has evaluated effective treatments to reduce cannabis use among high potency cannabis users. Some research has found that the non-intoxicating cannabinoid cannabidiol reduces cannabis use and cannabis use disorder-related symptoms, such as affective disturbance and withdrawal. Results of these studies are promising but limited to synthetic or isolated forms of cannabidiol. Objective: Conduct a placebo-controlled randomized control trial comparing the effects of hemp-derived cannabidiol on reducing Δ9-tetrahydrocannabinol use in concentrate users with cannabis use disorder. Methods: Design. Double-blind, three-arm randomized placebo-controlled trial. Setting. University in the Denver-Boulder, CO, USA area. Study population. Community members who are heavy, stable cannabis concentrate users that meet criteria for at least moderate cannabis use disorder and are seeking to decrease or stop cannabis use. Data. Self-report demographics, substance use, and mental health characteristics, blood and urine based biomarkers and anthropometrics. Outcomes. Affective, physiological, and physical withdrawal symptoms, Δ9-tetrahydrocannabinol use. Analysis. Three-group ANOVAs and χ2 tests will be used to compare baseline variables between groups. Characteristics that differ between groups will be evaluated as potential covariates in subsequent analyses. A multilevel modeling framework will be used for primary outcome analysis to account for the repeated observations nested within participants over time. Pairwise post-hoc simple effects tests will be conducted to confirm patterns of differences. Trial registration: ClinicalTrials.gov NCT06107062. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to examine the acute effects of legal-market cannabis on regular cannabis users' subjective responses to exercise in a controlled laboratory environment. Background: Given the stereotype that cannabis is associated with extreme sedentary behavior, there are concerns that cannabis legalization may exacerbate the US physical inactivity epidemic. However, despite these concerns, recent years have seen considerable public interest in the use of cannabis concurrently with exercise (e.g., running). Methods: The present study compared participants' experiences of exercise without cannabis to their experiences of exercise after acute ad libitum use of one of two commercially available cannabis flower products: a Δ9-tetrahydrocannabinol-dominant or a cannabidiol-dominant product. Participants (N = 42) were regular cannabis users between the ages of 21 and 39 years (mean = 30.81 years, standard deviation = 4.72 years). Results: Although participants reported a more positive affect (p < 0.001), enjoyment (p < 0.001), and runner's high symptoms (p < 0.001) during their cannabis (vs non-cannabis) exercise appointment, they also reported more exertion (p = 0.04). Pain levels were very low and did not differ between appointments (p = 0.45). Effects appeared to depend, in part, on cannabinoid content; there was a larger difference in enjoyment (p = 0.02), and a smaller difference in exertion (p = 0.02), between the cannabis and non-cannabis exercise appointments among participants in the cannabidiol (vs Δ9-tetrahydrocannabinol) condition. Conclusions: To our knowledge, this is the first study to investigate the acute effects of commercially available cannabis on subjective responses to exercise in a laboratory environment. Our findings suggest that, among regular cannabis users who use cannabis in combination with exercise, cannabis use prior to exercise may lead to increases in both positive and negative aspects of the subjective exercise experience. Research using diverse samples, exercise modalities, and methodologies (e.g., placebo-controlled trials) is needed to establish the generalizability of these findings. [ABSTRACT FROM AUTHOR]

This study utilized a randomized control trial to examine whether structural changes in the precuneus, insula, caudate, hippocampus, and putamen were related to exercise. A total of 197 healthy older adults with no evidence of dementia participated in moderate-intensity interval training or low-intensity continuous training for 16 weeks. Size decreased in the right hippocampus such that the effect of time was significant but the interaction with condition was not. For the left hippocampus, size decreased in the low-intensity continuous training condition but increased in the moderate-intensity continuous training plus interval training condition at the trend level. Finally, there was a significant time-by-condition interaction such that the thickness of the left insula increased for low-intensity continuous training and decreased for moderate-intensity continuous training plus interval training. Few structural changes were associated with the exercise intervention. Future studies should examine the effects of exercise on brain structure in high-risk or clinical populations for a longer period of time. [ABSTRACT FROM AUTHOR]

Background: The increasing availability of legal-market cannabis products has raised many questions about potential harms and benefits of increased use. In particular, concerns have been raised about the possible negative impact of cannabis use on behavioral determinants of obesity and chronic disease, including diet and exercise. However, previous research is mixed and has largely relied on cross-sectional survey data and coarse measurements of cannabis use, underscoring the need for more rigorous research designs. Purpose: The present study utilized longitudinal daily diary data to assess whether exercise and diet patterns differed between cannabis users and non-users and, within cannabis users, whether legal-market cannabis use, diet, and exercise covaried within individuals across time and based on cannabinoid content. Methods: A sample of 98 participants (77 cannabis users, 21 non-users) completed a baseline appointment and a 30-day daily diary study assessing their daily cannabis use, diet, and exercise. Cannabis users were quasi-randomly assigned to use either a THC-dominant flower product (n = 36) or a CBD-containing flower product (n = 41) ad libitum over the course of the daily diary study. Participants were between the ages of 21 and 41 (M = 29.28) and were majority male (61.2%). Results: At baseline, there were no differences in BMI or exercise behavior between users and non-users. Likelihood of exercising and exercise minutes per day over the 30-day period also did not differ between users and non-users, nor did these outcomes differ on cannabis use vs. non-use days among cannabis using participants. In contrast, there was some evidence for a relationship between cannabis use and dietary measures. At baseline, non-users scored higher on the Healthy Eating Index than users. Daily data also indicated that users consumed marginally more salty snacks and fast food per day relative to non-users, and users consumed more fruits/vegetables and marginally more salty snacks on cannabis use days vs. non-use days. Interestingly, among users, no associations were dependent on the cannabinoid content of their assigned product. Conclusion: Findings suggest little association between cannabis use and exercise but underscore the need for further research on how cannabis use may impact dietary patterns. Future research should examine the impact of cannabis on non-behavioral pathways to obesity and chronic disease (e.g., metabolism). [ABSTRACT FROM AUTHOR]

Cannabis use is increasing among older adults. We examined whether cannabis use impacted results of an intervention to increase physical activity in sedentary adults aged 60 and over. Methods: We measured differences in body mass index (BMI), exercise behavior, and cardiovascular fitness between older adult cannabis users (N = 28) and nonusers (N = 136) participating in an exercise intervention trial. Results: BMI of cannabis users was significantly lower than non-users (p = .007). Cannabis users reported .70 more days of exercise on the Stanford 7-Day Physical Activity Recall than non-users at the 8-week timepoint (p = .068) and were 4.1 points higher on the exercise subscale of the Community Healthy Activities Model Program for Seniors at 16-weeks (p = .045). Neither baseline nor post-intervention fitness differed by cannabis use status, and cardiovascular fitness improved after intervention in the full sample. Conclusion: These preliminary data suggest that current cannabis use status is not associated with a negative impact on fitness and efforts to increase exercise in sedentary older adults. Future studies should collect more detailed information on patterns and forms of cannabis use to understand their potential health effects for older adults. [ABSTRACT FROM AUTHOR]

Insulin resistance and obesity are characterized by low nitric oxide (NO) bioavailability. Insulin sensitivity is improved with stimulation of NO generating pathways. Consumption of dietary nitrate (NO3-) increases NO formation, via NO3- reduction to nitrite (NO2-) by oral bacteria. We hypothesized that acute dietary nitrate (beet juice) ingestion improves insulin sensitivity in obese but not in nonobese adults. 12 nonobese (body mass index: 26.3±0.8 kg/m2 (mean ± SE)) and 10 obese adults (34.0±0.8 kg/m2) ingested beet juice, supplemented with 25 g of glucose (carbohydrate load: 75 g), with and without prior use of antibacterial mouthwash to inhibit NO3- reduction to NO2-. Blood glucose concentrations after beet juice and glucose ingestion were greater in obese compared with nonobese adults at 60 and 90 minutes (P=0.004). Insulin sensitivity, as represented by the Matsuda Index (where higher values reflect greater insulin sensitivity), was lower in obese compared with nonobese adults (P=0.009). Antibacterial mouthwash rinsing decreased insulin sensitivity in obese (5.7±0.7 versus 4.9±0.6) but not in nonobese (8.1±1.0 versus 8.9±0.9) adults (P=0.048). In conclusion, insulin sensitivity was improved in obese but not in nonobese adults following coingestion of beet juice and glucose when oral bacteria nitrate reduction was not inhibited. Obese adults may benefit from ingestion of healthy nitrate-rich foods during meals. [ABSTRACT FROM AUTHOR]

Intravenous administration of vitamin C has been shown to decrease oxidative stress and, in some instances, improve physiological function in adult humans. Oral vitamin C administration is typically less effective than intravenous, due in part to inferior vitamin C bioavailability. The purpose of this study was to determine the efficacy of oral delivery of vitamin C encapsulated in liposomes. On 4 separate randomly ordered occasions, 11 men and women were administered an oral placebo, or 4 g of vitamin C via oral, oral liposomal, or intravenous delivery. The data indicate that oral delivery of 4 g of vitamin C encapsulated in liposomes (1) produces circulating concentrations of vitamin C that are greater than unencapsulated oral but less than intravenous administration and (2) provides protection from ischemia--reperfusion-mediated oxidative stress that is similar to the protection provided by unencapsulated oral and intravenous administrations. [ABSTRACT FROM AUTHOR]

Improved endurance exercise performance in adult humans after sprint interval training (SIT) has been attributed to mitochondrial biogenesis. However, muscle protein synthesis (MPS) and mitochondrial biogenesis during SIT have not been measured, nor have sex-specific differences. We hypothesized that males and females would have similar rates of MPS, mitochondrial biogenesis, and synthesis of individual proteins during SIT. Deuterium oxide (D2O) was orally administered to 21 adults [11 male, 10 female; mean age, 23±1 yr; body mass index (BMI), 22.8±0.6 kg/m ; mean± se] for 4 wk, to measure protein synthesis rates while completing 9 sessions of 4-8 bouts of 30 s duration on a cycle ergometer separated by 4 min of active recovery. Samples of the vastus lateralis were taken before and 48 h after SIT. SIT increased maximum oxygen uptake (VO2max, males 43.4±2.1-44.0±2.3; females 39.5 + 0.942.5+1.3 ml/kg/min; P=0.002). MPS was greater in the males than in the females in the mixed (~150%; P < 0.001), cytosolic (~135%; P=0.038), and mitochondrial (~135%; P=0.056) fractions. The corresponding ontological clusters of individual proteins were significantly greater in the males than in the females (all P< 0.00001). For the first time, we document greater MPS and mitochondrial biogenesis during SIT in males than in females and describe the synthetic response of individual proteins in humans during exercise training. [ABSTRACT FROM AUTHOR]

The conversion of white adipose to the highly thermogenic beige adipose tissue has been proposed as a potential strategy to counter the unfavorable consequences of obesity. Three regulators of this conversion have recently emerged but information regarding their control is limited, and contradictory. We present two studies examining the control of these regulators. Study 1: In 10 young men, the plasma concentrations of irisin and fibroblast growth factor 21 (FGF21) were determined prior to and during activation of the sympathetic nervous system via hypoxic gas breathing (FIO2 = 0.11). The measurements were performed twice, once with and once without prior/concurrent sympathetic inhibition via transdermal clonidine administration. FGF21 was unaffected by basal sympathetic inhibition (338±113 vs. 295±80 pg/mL; P = 0.43; mean±SE), but was increased during hypoxia mediated sympathetic activation (368±135); this response was abrogated (P = 0.035) with clonidine (269±93). Irisin was unaffected by sympathetic inhibition and/or hypoxia (P>0.21). Study 2: The plasma concentration of irisin and FGF21, and the skeletal muscle protein content of fibronectin type III domain containing 5 (FNDC5) was determined in 19 young adults prior to and following three weeks of sprint interval training (SIT). SIT decreased FGF21 (338±78 vs. 251±36; P = 0.046) but did not affect FNDC5 (P = 0.79). Irisin was decreased in males (127±18 vs. 90±23 ng/mL; P = 0.045) and increased in females (139±14 vs. 170±18). Collectively, these data suggest a potential regulatory role of acute sympathetic activation pertaining to the browning of white adipose; further, there appears to be a sexual dimorphic response of irisin to SIT. [ABSTRACT FROM AUTHOR]