Alexander R. Keeble

ORCID: 0000-0001-5895-4315
Publications
Citations
Views
---
Saved
---
About
Contact & Profiles
Research Areas
  • Muscle Physiology and Disorders
  • Knee injuries and reconstruction techniques
  • Muscle metabolism and nutrition
  • Nutrition and Health in Aging
  • Adipose Tissue and Metabolism
  • Sports injuries and prevention
  • Vitamin D Research Studies
  • Cardiovascular and exercise physiology
  • Sports Performance and Training
  • Exercise and Physiological Responses
  • Histone Deacetylase Inhibitors Research
  • Telomeres, Telomerase, and Senescence
  • Tendon Structure and Treatment
  • Cardiovascular Effects of Exercise
  • Vitamin C and Antioxidants Research
  • Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Total Knee Arthroplasty Outcomes
  • Chronic Obstructive Pulmonary Disease (COPD) Research
  • Tissue Engineering and Regenerative Medicine
  • Immune cells in cancer
  • Hydrogen's biological and therapeutic effects
  • Osteoarthritis Treatment and Mechanisms
  • Intensive Care Unit Cognitive Disorders
  • Mitochondrial Function and Pathology
  • Cancer-related gene regulation

University of Kentucky
2021-2025

University of Illinois Urbana-Champaign
2019-2022

Abstract Muscle inflammation and fibrosis underlie disuse‐related complications may contribute to impaired muscle recovery in aging. Cellular senescence is an emerging link between inflammation, extracellular matrix (ECM) remodeling poor after disuse. In rodents, metformin has been shown prevent cellular senescence/senescent associated secretory phenotype (SASP), making it a potentially practical therapeutic solution. Thus, the purpose of this study was determine older adults if monotherapy...

10.1111/acel.13936 article EN cc-by Aging Cell 2023-07-24

Murine exercise models can provide information on factors that influence muscle adaptability with aging, but few translatable solutions exist. Progressive weighted wheel running (PoWeR) is a simple, voluntary, low-cost, high-volume endurance/resistance approach for training young mice. In the current investigation, aged mice (22-mo-old) underwent modified version of PoWeR 8 wk. Muscle functional, cellular, biochemical, transcriptional, and myonuclear DNA methylation analyses an encompassing...

10.1093/function/zqac027 article EN cc-by-nc Function 2022-01-01

Exercise is a potent stimulus for combatting skeletal muscle ageing. To study the effects of exercise on in preclinical setting, we developed combined endurance-resistance training mice called progressive weighted wheel running (PoWeR). PoWeR improves molecular, biochemical, cellular and functional characteristics promotes aspects partial epigenetic reprogramming when performed late life (22-24 months age). In this investigation, leveraged pan-mammalian DNA methylome arrays tandem...

10.1113/jp286681 article EN cc-by-nc-nd The Journal of Physiology 2024-07-26

Musculoskeletal disorders contribute substantially to worldwide disability. Anterior cruciate ligament (ACL) tears result in unresolved muscle weakness and posttraumatic osteoarthritis (PTOA). Growth differentiation factor 8 (GDF8) has been implicated the pathogenesis of musculoskeletal degeneration following ACL injury. We investigated GDF8 levels ACL-injured human skeletal serum tested a humanized monoclonal antibody against placebo mouse model PTOA (surgically induced tear). In patients,...

10.1126/sciadv.adi9134 article EN cc-by-nc Science Advances 2023-11-29

Skeletal muscle aging is a multidimensional pathology of atrophy, reduced strength, and oxidative damage. Although some molecular targets may mediate both hypertrophic adaptations in muscle, their responsiveness humans relationship with functional outcomes like strength remain unclear. Promising therapeutic to combat apelin, vitamin D receptor (VDR), spermine oxidase (SMOX) have been investigated preclinical models but the adaptive response not well defined. In an exploratory investigation,...

10.1152/japplphysiol.00186.2022 article EN Journal of Applied Physiology 2022-07-14

Abstract Skeletal muscle adaptation to external stimuli, such as regeneration following injury and hypertrophy in response resistance exercise, are blunted with advanced age. The accumulation of senescent cells, along defects myogenic progenitor cell (MPC) proliferation, have been strongly linked contributing factors age-associated impairment adaptation. p53 plays an integral role all these processes, upregulation causes apoptosis cells prevents mitotic catastrophe MPCs from old mice. goal...

10.1007/s11357-023-00976-2 article EN cc-by GeroScience 2023-10-24

Background: Anterior cruciate ligament (ACL) tear (ACLT) leads to protracted quadriceps muscle atrophy. Protein turnover largely dictates size and is highly responsive injury loading. Regulation of molecular protein synthetic machinery after ACLT has been unexplored, limiting development targeted therapies. Purpose: To define the effect on (1) activation catabolic signaling within biopsy specimens from human participants (2) time course alterations synthesis its regulation in a mouse ACL...

10.1177/03635465221135769 article EN The American Journal of Sports Medicine 2022-12-07

Abstract Human hallmarks of sarcopenia include muscle weakness and a blunted response to exercise. Nicotinamide N-methyltransferase inhibitors (NNMTis) increase strength promote the regenerative capacity aged muscle, thus offering promising treatment for sarcopenia. Since human are recapitulated in (24-month-old) mice, we treated mice from 22 24 months age with NNMTi, intensive exercise, or combination both, compared skeletal adaptations, including grip strength, longitudinal running...

10.1038/s41598-024-66034-9 article EN cc-by Scientific Reports 2024-07-05

Knee osteoarthritis contributes substantially to worldwide disability. Post-traumatic (PTOA) develops secondary joint injury, such as ligament rupture, and there is increasing evidence suggesting a key role for inflammation in the aetiology of PTOA associated functional deficits. Colony stimulating factor 1 receptor (CSF1-R) has been implicated pathogenesis musculoskeletal degeneration following anterior cruciate (ACL) injury. We sought assess efficacy CSF1-R inhibition mitigate muscle...

10.1113/jp286815 article EN The Journal of Physiology 2024-12-22

Carbohydrate (CHO) ingestion is an established strategy to improve endurance performance. Race fuels should not only sustain performance but also be readily digested and absorbed. Potatoes are a whole-food-based option that fulfills these criteria, yet their impact on remains unexamined. We investigated the effects of potato purée during prolonged cycling subsequent vs. commercial CHO gel or water-only condition. Twelve cyclists (70.7 ± 7.7 kg, 173 8 cm, 31 9 yr, 22 5.1% body fat; means SD)...

10.1152/japplphysiol.00567.2019 article EN cc-by Journal of Applied Physiology 2019-10-17

BACKGROUND. Although 25-hydroxyvitamin D (25(OH)D) concentrations ≥30ng/mL are known to reduce injury risk and boost strength, the influence on anterior cruciate ligament reconstruction (ACLR) outcomes remains unexamined. This study aimed define vitamin signaling response ACLR, assess relationship between status muscle fiber cross-sectional area (CSA) bone density outcomes, discover receptor (VDR) targets post-ACLR.

10.1172/jci.insight.170518 article EN cc-by JCI Insight 2023-10-19

The ingestion of protein potentiates the stimulation myofibrillar synthesis rates after an acute bout resistance exercise. Protein supplementation (eating above Recommended Dietary Allowance) during training has been shown to maximize lean mass and strength gains in healthy young older adults. Here, contractile, oxidative, structural were assessed skeletal muscle response a moderate or higher diet early adaptive phase middle-aged myofibrillar, mitochondrial collagen 0-3 weeks is not further...

10.1113/jp281907 article EN The Journal of Physiology 2021-07-28

Joint injury is associated with protracted atrophy and weakness that poorly recovers; our objective was to define molecular effectors of lost muscle size, strength, plasticity following joint injury. We hypothesized epigenetic imprinting in impairs contributes poor functional recovery surgical repair. recruited a total sixteen ACL-injured participants from whom we obtained vastus lateralis biopsies Pre-, 7-days post-, 4-months post- reconstruction surgery (Sx) strength measures up 6-months...

10.1152/physiol.2024.39.s1.1574 article EN Physiology 2024-05-01

Injury to the acute cruciate ligament (ACL) disrupts musculoskeletal tissue architecture and function, leading atrophy weakness associated with development of posttraumatic osteoarthritis (PTOA). The objective this study was profile senescent cell burden across skeletal muscle knee joint capsule compartments ascertain effectiveness senolytic treatment in mitigation PTOA. Given unique features these tissues, we hypothesized that composition physiological consequence would differ among...

10.1152/physiol.2024.39.s1.1544 article EN Physiology 2024-05-01

Abstract Background Sepsis, mainly caused by bacterial infections, is the leading cause of in-patient hospitalizations. After discharge, most sepsis survivors suffer from long-term medical complications, particularly chronic skeletal muscle weakness. To investigate this condition in detail, we previously developed a murine severe sepsis-survival model that exhibits post-sepsis While mitochondrial abnormalities were present surviving mice, relationship between abnormal mitochondria and...

10.1186/s10020-024-00982-w article EN cc-by Molecular Medicine 2024-11-19

ABSTRACT Type 1 diabetes (T1D) is associated with low bone and muscle mass, increased fracture risk, impaired skeletal function. Myostatin, a myokine that systemically elevated in humans T1D, negatively regulates mass formation. We investigated whether pharmacologic myostatin inhibition mouse model of insulin‐deficient, streptozotocin (STZ)‐induced protective for muscle. DBA/2J male mice were injected low‐dose STZ (diabetic) or vehicle (non‐diabetic). Subsequently, insulin palmitate Linbits...

10.1002/jbm4.10833 article EN cc-by JBMR Plus 2023-10-26

The loss of muscle mass with age increases not only risk functional impairment, but also development and exacerbation cardiometabolic disease. While dietary protein intake habitual resistance exercise are traditional strategies to offset age-related decrements in lean mass, it is important define the role other regulatory nutrients this process. Dietary vitamin D (VD) has received particular interest as receptor (VDR) associated hypertrophy. Importantly, beyond being a significant source...

10.1093/cdn/nzab041_027 article EN cc-by-nc-nd Current Developments in Nutrition 2021-06-01

Anterior cruciate ligament (ACL) tears are debilitating sport-related injuries resulting in protracted quadriceps atrophy. Our group has previously shown lower satellite cell abundance with atrophy following ACL injury. Canonically, cells fuse into muscle fibers to maintain myonuclear density and injury, reduced compromises recovery. We aimed determine whether this loss of is causative or a consequence PURPOSE: To the role recovery from METHODS: Pax7CreER/CreER:Rosa26DTA/DTA mice were...

10.1249/01.mss.0000979804.51803.f5 article EN Medicine & Science in Sports & Exercise 2023-09-01

Yes-Associated Protein (YAP) is implicated as a regulator of the post-exercise skeletal muscle response through mechanical transduction. We recently observed that resistance exercise (RE) increased both total (t) and phosphorylated (p) YAP content, which correlated with extracellular signal-regulated kinase 1/2 (Erk1/2). Other anabolic signaling pathways (i.e., mTORC1) are known to be potentiated by combined stimuli RE protein ingestion during recovery. However, impact on t- p-muscle content...

10.1093/cdn/nzaa049_049 article EN cc-by-nc-nd Current Developments in Nutrition 2020-05-29
Coming Soon ...