Publications by authors named "Christiaan Leeuwenburgh"

Article Synopsis
  • Nuclear insertions of mitochondrial DNA segments (NUMTs) are dynamic genetic elements that arise from the ancient relationship between mitochondria and host cells, primarily found in areas of the genome linked to regulatory functions.
  • Recent research shows that stress-induced mitochondrial damage can trigger the release of mtDNA, leading to NUMT integration, which may be more common in aging tissues and linked to cognitive decline and cancer development.
  • The review emphasizes the importance of NUMTs in understanding aging and disease mechanisms, suggesting they could influence mitochondrial-nuclear communication, inflammation, and cellular aging, opening avenues for new biomarkers and treatments.
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Aerobic exercise lowers blood pressure (BP) with varying effects in hypertensive adults, potentially due to age-related nicotinamide adenine dinucleotide (NAD) metabolism dysregulation. This pilot randomized clinical trial (RCT) tested the efficacy of combining aerobic exercise with the NAD booster nicotinamide riboside (NR) to enhance BP control. In this double-blinded RCT, 54 sedentary adults (≥ 55 years) with mean daytime systolic BP (SBP) ≥ 130 mmHg were randomized to 6 weeks of 1000 mg/day of NR combined with 3 days/week of supervised 30-min walking exercise (NR + Ex), Placebo combined with the same exercise regimen (PL + Ex), or NR alone (NR).

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This substudy utilised data from a prospective, longitudinal study aimed to investigate associations between systemic inflammation, wound bioburden, total bacterial counts and wound healing outcomes over 8 weeks in older adults with chronic venous leg ulcers (CVLUs). Participants were receiving standardised weekly wound debridement. Blood and wound tissue samples were collected at baseline and Weeks 2, 4, 6 and 8, or until the wound was healed.

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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.

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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.

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Thoracic surgery rapidly induces weakness in human diaphragm fibers. The dysfunction is thought to arise from combined effects of the surgical procedures and inactivity. This project tested whether brief bouts of intraoperative hemidiaphragm stimulation would mitigate slow and fast fiber loss of force in the human diaphragm.

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Objectives: Cellular senescence, characterized by a marked and multifactorial senescence-associated secretory phenotype (SASP), is a potential unifying mechanism of aging and chronic disease. Most studies of the SASP have focused on frailty and other functional outcomes. Senescent cells have been detected in the brains of patients with Alzheimer's disease, but few studies have examined associations between plasma SASP markers and cognition.

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Medium-sized scientific conferences held in hotels large enough to accommodate all participants increase opportunities for constructive discussion during breaks, and for evenings that bring together young and senior experts of basic sciences and clinical specialties. Time for group discussions offer opportunities for new collaborations and for jobs for young researchers. Since 1991 the Padova Muscle Days have offered collaborative opportunities that have matured into innovative multidisciplinary results to the point that it came naturally for us to underline it with a neologism now included in the title of the 2025 event: "Mobility Medicine".

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Background: VM202 is a plasmid encoding two isoforms of hepatocyte growth factor. In preclinical studies, hepatocyte growth factor stimulated angiogenesis and muscle regeneration. This preliminary clinical trial tested the hypothesis that VM202 injections in gastrocnemius muscle would improve walking performance in people with mild to moderate and symptomatic lower extremity peripheral artery disease (PAD).

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This special issue of the Journal of Experimental Gerontology explores the dynamic interplay between microbiomes and aging-related conditions. The four selected studies highlight the role of microbiota in Alzheimer's disease, cancer immunotherapy, myocardial infarction and tryptophan metabolism, providing insights into how microbiomes influence health and disease in aging. These studies underscore the potential for microbiome-targeted interventions to mitigate aging-related disorders and improve the quality of life for older adults.

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Mega scientific conferences increasingly suffer from the need for short and poster presentations without discussion. An alternative is to organize workshops in hotels large enough to accommodate all participants. This significantly increases the opportunities for constructive discussion during breakfasts, lunches, dinners and long evenings that can bring together experts of scientific and clinical sub-specialties and young fellows.

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Article Synopsis
  • The study examined the relationship between mitochondrial quality control markers, serum inflammatory markers, and muscle power in older adults, utilizing data from a project at the University of Florida.
  • Forty-three older adults participated, with muscle power assessed using two different tests and various methodologies implemented to measure muscle and inflammatory markers.
  • Results showed significant associations between certain mitochondrial and inflammatory markers and muscle power, with differences noted based on the specific assessment method used.
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Article Synopsis
  • * The study aims to evaluate a remotely delivered exercise program through a mobile app for improving physical function in older sepsis survivors, addressing challenges related to traditional rehabilitation.
  • * The ongoing research will enroll 40 participants, randomly assigning them to either the exercise intervention or a control group, with both using a tablet-based health app for monitoring progress.
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Article Synopsis
  • Globally, while people are living longer, many experience a decline in health due to age-related diseases, highlighting the need for better classification systems to address these issues.
  • A consensus meeting with 150 experts established criteria for identifying ageing-related pathologies, requiring a 70% agreement for approval among participants.
  • The agreed criteria focus on conditions that progress with age, contribute to functional decline, and are backed by human studies, setting a foundation for future classification and staging efforts.
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Background: Mitochondrial abnormalities exist in lower-extremity peripheral artery disease (PAD), yet the association of the ankle-brachial index (ABI) with mitochondrial respiration in gastrocnemius muscle is unknown. The association of gastrocnemius mitochondrial respiration with 6-minute walk distance in PAD is unknown. This objective of this study was to describe associations of the ABI with mitochondrial respiratory function in gastrocnemius muscle biopsies and associations of gastrocnemius mitochondrial respirometry with 6-minute walk distance in people with and without PAD.

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Background: Chat Generative Pre-trained Transformer (ChatGPT) and other ChatBots have emerged as tools for interacting with information in manners resembling natural human speech. Consequently, the technology is used across various disciplines, including business, education, and even in biomedical sciences. There is a need to better understand how ChatGPT can be used to advance gerontology research.

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The natural polyphenol resveratrol (RSV) might counteract the skeletal muscle age-related loss of muscle mass and strength/function partly acting on mitochondria. This work analysed the effects of a six-week administration of RSV (50 mg/kg/day) in the oxidative Soleus (Sol) skeletal muscle of old rats (27 months old). RSV effects on key mitochondrial biogenesis proteins led to un unchanged amount of SIRT1 protein and a marked decrease (60 %) in PGC-1α protein.

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People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans.

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Among all non-communicable diseases, Cardiovascular Diseases (CVDs) stand as the leading global cause of mortality. Within this spectrum, Myocardial Infarction (MI) strikingly accounts for over 15 % of all deaths. The intricate web of risk factors for MI, comprising family history, tobacco use, oral health, hypertension, nutritional pattern, and microbial infections, is firmly influenced by the human gut and oral microbiota, their diversity, richness, and dysbiosis, along with their respective metabolites.

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Article Synopsis
  • * The body regulates iron levels through intestinal absorption, as excretion is inefficient; aging can disrupt this balance, leading to deficiencies or excess iron.
  • * Regular assessment of iron status and adherence to daily intake guidelines is crucial for older adults to maintain healthy iron levels and minimize health risks.
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Objectives: Low cholesterol levels in early sepsis patients are associated with mortality. We sought to test if IV lipid emulsion administration to sepsis patients with low cholesterol levels would prevent a decline or increase total cholesterol levels at 48 hours.

Design: Phase II, adaptive, randomized pilot clinical trial powered for 48 patients.

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Aging is associated with multiple physiological changes that contribute synergistically and independently to physical disability and the risk of chronic disease. Although the etiology of age-related physical disability is complex and multifactorial, the decline in mitochondrial function appears to coincide with the progression of functional decline in many older adults. The reason why there is a decrease in mitochondrial function with aging remains elusive, but emerging science indicates that both fuel metabolism and circadian rhythms can influence mitochondrial function.

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Article Synopsis
  • * The research assessed how proteins from senescent cells relate to mobility disabilities in older adults and examined the impact of physical activity on these proteins.
  • * Among nearly 1,400 participants, significant links were found between certain senescence proteins and mobility issues, while physical activity was associated with notable decreases in several senescence-related proteins over time.
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