About

Christiaan Leeuwenburgh, PhD, is a faculty member associated with UF Health. The available page text does not provide specific details about his research focus, background, or key contributions. Therefore, a detailed biography cannot be generated from the provided information.

Research topics

• Medicine
• Internal medicine
• Intensive care medicine
• Physical therapy
• Physical medicine and rehabilitation
• Psychiatry
• Bioinformatics
• Gerontology
• Cardiology
• Immunology
• Pathology
• Genetics
• Neuroscience
• Psychology

Selected publications

• Feasibility of home-based, remotely delivered exercise training to improve physical function in older sepsis survivors: a pilot randomized controlled trial

  GeroScience · 2026-05-21

  articleOpen access

  Sepsis survivors frequently experience post-discharge physical function decline and encounter logistical barriers to participation in traditional outpatient rehabilitation. This pilot study examined the feasibility, safety, and preliminary efficacy of a remotely delivered, home-based exercise program on physical function in older sepsis survivors. In this single-blinded, randomized controlled trial (RCT), sepsis survivors aged ≥ 55 years were randomized to (a) 12 weeks of avatar-guided, progressive exercise training group (EX) or (b) a standard care control group (CO). Primary outcomes were feasibility (retention, adherence) and safety (adverse events), whereas secondary outcomes were changes in the 30-s Sit-to-Stand (30SSTS), 4-Stage Balance Test (4SBT), Timed Up-and-Go (TUG) tests, and Eastern Cooperative Oncology Group/Zubrod's (ECOG/Zubrod) performance status score. Twenty-one participants were randomized to either EX (n = 10, mean age = 69.6 ± 8.5 years, 40% females) or CO (n = 11, mean age = 72.3 ± 7.9 years, 45% females). Mean retention was 95% and adherence to exercise training was 76%. Thirty-four adverse events (AEs) occurred (EX = 11; CO = 16; consented but not randomized = 7 events), including four serious AEs that were unrelated to the study. The EX group showed trends toward improvements in lower-extremity strength (30SSTS: 1.14 ± 2.91 repetitions, Cohen's d = 0.393) and balance (4SBT: 5.07 ± 4.75 s, d = 1.07), whereas the CO group showed no change in balance on the 4SBT (0.01 ± 4.38 s, d = 0.003) and trends toward decline in lower-extremity strength on the 30SSTS (- 0.88 ± 0.99 repetitions, d = - 0.883). TUG performance showed modest trends toward reductions in completion time in both groups (EX: - 1.42 ± 6.58 s, d = - 0.216; CO: - 1.27 ± 2.73 s, d = - 0.466). ECOG/Zubrod scores showed a modest trend toward improvement in the EX group subset. This pilot RCT demonstrated that a 12-week, remotely delivered exercise program was safe and feasible for older sepsis survivors and showed preliminary signals of positive change in lower-extremity strength, balance, and functional status, which warrants testing efficacy in an adequately powered Phase IIb RCT. ClinicalTrials.gov NCT05568511.

  PublisherOA PDFDOI

• Intrinsic capacity–frailty phenotypes and subclinical inflammation in community-dwelling octogenarians: A cross-sectional analysis from the ilSIRENTE study

  Experimental Gerontology · 2026-01-06 · 4 citations

  articleOpen access

  Chronic low-grade inflammation contributes to frailty and functional decline in aging. Intrinsic capacity (IC), defined as the composite of physical and mental reserves, complements frailty assessment by reflecting functional resilience. This cross-sectional analysis used baseline data from the ilSIRENTE cohort to examine the relationship between IC–frailty phenotypes and systemic inflammation in community-dwelling octogenarians and identify IC domains most closely related to inflammatory burden. IC was assessed across five domains (locomotion, cognition, vitality, psychological well-being, and sensory function), rescaled to a 0–100 range, and combined with frailty status to define four IC–frailty phenotypes (concordant frail, discordant low IC, discordant high IC, concordant robust). Plasma C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured, and a composite inflammatory burden score (0–3) was derived. The analysis included 311 participants (mean age 85.4 ± 4.7 years, 66.6 % women). Median CRP, IL-6, and TNF-α levels increased progressively from concordant robust to concordant frail groups ( p < 0.01). In the fully adjusted model, concordant frail participants had higher inflammation compared with concordant robust (β = 0.71; 95 % CI 0.04–1.37; p = 0.03), while discordant high IC and discordant low IC showed intermediate values without statistical significance. A significant linear trend was observed across ordered phenotypes (β per category increment = 0.21, 95 % CI 0.06 to 0.37). Locomotion and vitality emerged as the domains most strongly linked to inflammation. IC–frailty phenotypes show a biological gradient of subclinical inflammation, with higher IC having lower inflammation levels. Preserved locomotion reflects key functional correlates of resilience and vitality in advanced age. • Intrinsic capacity–frailty phenotypes display a biological inflammation gradient. • Reduced intrinsic capacity is associated with elevated CRP, IL-6, and TNF-α levels. • Locomotion and vitality drive the link between functional decline and inflammation. • Results suggest impaired resilience as a pathway of inflammaging in late life. • Integrating intrinsic capacity with biomarkers refines geroscience models of aging.

  PublisherDOI

• Iron Metabolism and Muscle Aging: Where Ferritinophagy Meets Mitochondrial Quality Control

  Cells · 2025-05-03 · 10 citations

  reviewOpen accessCorresponding

  In older adults with reduced physical performance, an increase in the labile iron pool within skeletal muscle is observed. This accumulation is associated with an altered expression of mitochondrial quality control (MQC) markers and increased mitochondrial DNA damage, supporting the hypothesis that impaired MQC contributes to muscle dysfunction during aging. The autophagy-lysosome system plays a critical role in MQC by tagging and engulfing proteins and organelles for degradation in lysosomes. The endolysosomal system is also instrumental in transferrin recycling, which, in turn, regulates cellular iron uptake. In the neuromuscular system, the autophagy-lysosome system supports the structural integrity of neuromuscular junctions, and its dysfunction contributes to muscle atrophy. While MQC was thought to protect against iron-induced cell death, the discovery of ferroptosis, a form of iron-dependent cell death, has highlighted a complex interplay between MQC and iron-inflicted damage. Ferritinophagy, the autophagic degradation of ferritin, if overactivated, can induce ferroptosis. Alternatively, aging may impair ferritinophagy, leading to ferritin accumulation and the release of toxic labile iron under stress, exacerbating oxidative damage and cellular senescence. Physical activity supports muscle health also by preserving mitochondrial quantity and quality and enhancing bioenergetics. However, therapeutic strategies for preventing or reversing physical function decline in aging are still lacking due to the insufficient understanding of the underlying mechanisms. Unveiling how disruptions in iron homeostasis impact muscle quality in older adults may allow for the development of therapeutic strategies targeting iron handling to alleviate age-associated muscle decline.

  PublisherOA PDFDOI

• Senescence-Associated Secretory Phenotypes in Middle-to-Older Age Individuals with High Impact Pain at Risk for Knee Osteoarthritis

  Journal of Pain · 2025-04-01

  article
  PublisherDOI

• Disentangling the Distinct Effects of Calorie Restriction versus Time-Restricted Eating on Longevity Pathways: Calorie Deficit or Fasting Window?

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• Metformin to Improve Walking Performance in Lower Extremity Peripheral Artery Disease

  JAMA · 2025-11-08 · 3 citations

  articleOpen access

  Importance: Lower extremity peripheral artery disease (PAD) is a disabling cardiovascular condition that impairs walking ability. Few effective therapies improve walking performance in people with PAD. Metformin is a widely available and inexpensive therapy for type 2 diabetes with pleiotropic effects that include activating AMP-activated protein kinase, reducing oxidative stress, and stimulating endothelial nitric oxide synthase (eNOS). Objective: To determine whether metformin improves 6-minute walk distance, compared with placebo, in people with PAD and without diabetes at 6-month follow-up. Design, Setting, and Participants: Randomized double-blind clinical trial involving 4 centers in the US. Enrollment began May 23, 2017, and ended on February 17, 2025, with 202 of the targeted 212 (95%) enrolled, due to funding limitations. Participants were adults aged 50 years and older with PAD. Final follow-up occurred August 19, 2025. Interventions: Participants with PAD were randomized to receive either metformin (n = 97) or placebo (n = 105) for 6 months. Main Outcomes and Measures: The primary outcome was 6-month change in 6-minute walk distance (minimum clinically important difference, 8 to 20 m). Secondary outcomes were maximal treadmill walking time, pain-free treadmill walking time, the Walking Impairment Questionnaire distance and speed scores, the Short-Form 36 physical functioning score, and brachial artery flow-mediated dilation. Results were adjusted for site and the baseline value for each outcome measure. Results: Of 202 randomized patients (mean [SD] age, 69.6 [8.4] years, 56 [28%] female, 79 [39%] Black), 179 (89%) completed 6-month follow-up. Metformin did not significantly improve 6-minute walk distance compared with placebo (metformin: 358.6 to 353.2 m, within-group change: -5.4 m; placebo: 359.8 to 354.5 m, within-group change: -5.3 m, adjusted between-group difference: 1.1 m [95% CI, -16.3 to 18.6 m]; P = .90). Compared with placebo, metformin did not significantly improve any secondary outcomes. The most common serious adverse events were cardiovascular events (3.1% for metformin and 1.9% for placebo). The most common nonserious adverse events were indigestion/stomach upset (64.9% for metformin and 40.6% for placebo) and headache (37.2% for metformin and 49.5% for placebo). Conclusions and Relevance: Among people with PAD without diabetes, metformin did not improve 6-minute walk distance at 6-month follow-up compared with placebo. These results do not support metformin for improving walking performance in patients with PAD. Trial Registration: ClinicalTrials.gov Identifier: NCT03054519.

  PublisherOA PDFDOI

• Exploring age-related iron dysregulation: effects on longevity, body size, and behavior in C. elegans

  Experimental Gerontology · 2025-07-03

  articleOpen accessCorresponding

  Age-related iron accumulation is widely observed in various species and significantly impacts physiological processes. However, systematic investigation into how age-related iron dysregulation affects different life traits is still limited. This study utilizes the model organism C. elegans to examine the roles of iron regulatory genes throughout different life stages, focusing on their effects on iron homeostasis, longevity, mobility, size, and mechanosensation. Our expression analysis indicated that most iron-related genes are generally upregulated by day 15, with some peaking earlier, suggesting their crucial role in mid-life iron regulation. Lifespan assays revealed that certain mutants of non-transferrin bound iron (NTBI) uptake regulators, such as smf-1 and smf-3, are linked to extended lifespans, while zipt-17 mutants showed slightly reduced longevity. Mobility assessments indicated significant declines in speed among several mutant strains by day 7, pointing to mobility issues related to altered iron metabolism. Body size measurements varied considerably among mutant strains, with some demonstrating significant changes over time. Behavioral analyses found that most strains exhibited mechanosensory responses similar to wild-type worms at day 1; however, certain mutants displayed different rates of response reduction by day 7. FerroOrange staining confirmed increased iron accumulation with age in most mutant strains, except for zipt-16 and zipt-17, highlighting the connection between iron regulation and aging. Collectively, our current findings demonstrate that iron regulatory genes in C. elegans play diverse and critical roles in maintaining iron homeostasis, influencing lifespan, mobility, body size, and behavioral responses throughout the organism's life. These findings deepen our understanding of iron regulation's impact on health and aging in C. elegans.

  PublisherDOI

• Exploring senescence markers as potential drivers of osteoarthritis pain in aging adults

  Experimental Gerontology · 2025-10-30 · 3 citations

  reviewOpen access

  Senescent cells (SnCs) contribute to various age-related diseases, such as osteoarthritis (OA), a degenerative joint condition that causes persistent pain and reduces physical functioning in older adults. The pathogenesis of OA includes subchondral bone remodeling, synovial inflammation, and cartilage breakdown. Cellular senescence, particularly the pro-inflammatory senescence-associated secretory phenotype (SASP), may have a pivotal role in the progression of OA. SASP factors could exacerbate OA by releasing inflammatory cytokines, chemokines, and proteases, which sensitize nociceptors and accelerate degenerative joint processes, thereby contributing to the chronic pain experienced by OA patients. This contribution of SASPs in chronic pain may lead to mobility limitations and decreased independence of individuals. Thus, the interplay between SASP-driven inflammation and OA pathogenesis may be critical for understanding knee OA pain and functional impairment in older adults. Here, we aim to discuss the parallels between SASP-driven inflammation and OA pathophysiology, which could identify novel therapeutic targets for improving pain management and treatment outcomes in OA. • Cellular senescence and SASP may drive age-related OA and pain through inflammation, joint degeneration, and sensitization of joint nociceptors. • Replicative and stress-induced senescence, triggered by factors like DNA damage and oxidative stress, accelerates aging and potentially OA progression. • Cellular senescence accelerates epigenetic modifications, which may contribute to OA pathogenesis. • Senotherapeutics targeting SASP factors may slow OA progression and manage pain.

  PublisherDOI

• Home-Based, Remotely-Delivered Exercise Training to Improve Physical Function of Middle-aged and Older Sepsis Survivors – the HEAL Sepsis Trial (Preprint)

  2025-09-16

  articleOpen access

  <sec> <title>BACKGROUND</title> Sepsis survivors frequently experience post-discharge physical function decline and encounter logistical barriers to participation in traditional outpatient rehabilitation. </sec> <sec> <title>OBJECTIVE</title> This pilot study examined the feasibility, safety, and preliminary efficacy of a remotely delivered, home-based exercise program on physical function in middle-age and older sepsis survivors. </sec> <sec> <title>METHODS</title> In this single-blinded, randomized controlled trial (RCT), we included sepsis survivors aged ≥55 years old and randomized them to 12 weeks of avatar-guided, progressive exercise training group (EX) or to a standard care control group (CO). Primary outcomes were feasibility (retention, adherence) and safety (adverse events), whereas secondary outcomes were changes in the 30-second Sit-to-Stand (30SSTS), 4-Stage Balance Test (4SBT), Timed Up-and-Go tests, and Eastern Cooperative Oncology Group/Zubrod's (ECOG/Zubrod) performance status score. Secondary outcomes were summarized as mean change, standard deviation, and effect sizes. </sec> <sec> <title>RESULTS</title> Twenty-one participants were randomized to either EX (n=10, mean age=69.6±8.5 years, 40% females) or CO (n=11, mean age=72.3±7.9 years, 45% females). Mean retention in the study was 95% and adherence to exercise training was 76%. Thirty-four adverse events (AEs) occurred (EX=12; CO=22 events), including four serious AEs that were unrelated to the study. The EX group demonstrated positive direction of change in lower-extremity strength (30SSTS: 1.14±2.91 repetitions, Cohen’s d=0.393) and balance (4SBT: 5.07±4.75 seconds, d=1.07). In contrast, the CO group showed minimal change in balance on the 4SBT (0.01±4.38 seconds, d=0.003) and a negative direction of change in lower-extremity strength on the 30SSTS (−0.88±0.99 repetitions, d=−0.883). Timed Up-and-Go performance showed modest reductions in completion time in both groups (EX: −1.42±6.58 seconds, d=−0.216; CO: −1.27±2.73 seconds, d=−0.466). ECOG/Zubrod scores also showed a positive direction of change in the EX group. </sec> <sec> <title>CONCLUSIONS</title> This pilot RCT demonstrated that a 12-week, remotely delivered exercise program was safe and feasible for middle-aged and older sepsis survivors. Preliminary signals of positive change in lower-extremity strength, balance, and functional status were observed, supporting the need for evaluation in a fully powered Phase IIb RCT targeting individuals at risk for post-discharge physical function decline. </sec> <sec> <title>CLINICALTRIAL</title> ClinicalTrials.gov NCT05568511. </sec>

  PublisherDOI

• Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice

  GeroScience · 2025-09-19 · 4 citations

  articleOpen access

  Mice bred in 2021 were tested by the Interventions Testing Program (ITP) for possible lifespan benefits of 2BAct (2BA), dichloroacetate (DCA), Epicatechin (EPI), Forskolin (FSK), Halofuginone (HAL) and Mitoglitazone (MIT). All agents were administered in the diet ad libitum beginning at 7 months of age. In male mice, EPI increased median lifespan by ~ 5%, and HAL and MIT each increased median lifespan by ~ 9%. EPI and HAL, but not MIT, increased 90% survival. In addition to adding 3 new agents to the list of interventions identified by the ITP that extend lifespan, this report continues the strong male bias in the efficacy of life-extending drugs identified so far.

  PublisherDOI

Recent grants

• NIH Grant R01AG017994

  NIH · $2.9M · 2013

• PICS: A New Horizon for Surgical Critical Care

  NIH · $17.0M · 2014–2020

• PICS: A New Horizon for Surgical Critical Care

  NIH · $4.5M · 2014–2019

• NIH Grant R01AG021042

  NIH · $1.7M · 2009

• NIH Grant R01DK09011504

  NIH · $319k · 2017

Frequent coauthors

• Emanuele Marzetti

  Università Cattolica del Sacro Cuore

  260 shared

• Lyle L. Moldawer

  Florida College

  143 shared

• Stephen D. Anton

  University of Florida

  142 shared

• Stephanie E. Wohlgemuth

  University of Florida

  125 shared

• Riccardo Calvani

  Agostino Gemelli University Polyclinic

  120 shared

• Philip A. Efron

  University of Florida

  113 shared

• Marco Pahor

  University of Florida

  113 shared

• Frederick A. Moore

  University Hospitals Birmingham NHS Foundation Trust

  111 shared