Publications by authors named "Robert T Mankowski"

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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Critical illness-induced muscle wasting is associated with poor in-hospital and long-term outcomes, but prevention strategies are lacking. Critical illness elicits muscle wasting through upregulation of protein degradation and downregulation of protein synthesis via primary (i.e.

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Excess cellular senescence contributes to age-related increases in frailty and reductions in skeletal muscle strength. In the present study, we determined the efficacy of oral intermittent treatment (1 week on-2 weeks off-1 week on) with the natural flavonoid senolytic fisetin to improve frailty and grip strength in old mice. Further, the effects of fisetin on physical function were evaluated in young mice.

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Article Synopsis
  • Ageing is a growing global concern, with projections that by 2030, one in six people will be 60 or older, highlighting the need to understand the biological processes and healthcare challenges associated with ageing.
  • The World Health Organization defines intrinsic capacity (IC) as the collective physical and mental abilities of an individual, with five vital components: locomotion, cognition, psychological, sensory, and vitality capacity (VC).
  • The review emphasizes the benefits of exercise in maintaining VC among older adults, discussing its positive effects on energy metabolism, neuromuscular function, immune response, mitochondrial health, and gene methylation, while also identifying potential areas for future research and interventions.
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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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Objective: To evaluate the persistence of intestinal microbiome dysbiosis and gut-plasma metabolomic perturbations following severe trauma or sepsis weeks after admission in patients experiencing chronic critical illness (CCI).

Summary: Trauma and sepsis can lead to gut dysbiosis and alterations in the plasma and fecal metabolome. However, the impact of these perturbations and correlations between gut dysbiosis and the plasma metabolome in chronic critical illness have not been studied.

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  • * 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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Background: Sepsis and trauma are known to disrupt gut bacterial microbiome communities, but the impacts and perturbations in the fungal (mycobiome) community after severe infection or injury, particularly in patients experiencing chronic critical illness (CCI), remain unstudied.

Methods: We assess persistence of the gut mycobiome perturbation (dysbiosis) in patients experiencing CCI following sepsis or trauma for up to two-to-three weeks after intensive care unit hospitalization.

Results: We show that the dysbiotic mycobiome arrays shift toward a pathobiome state, which is more susceptible to infection, in CCI patients compared to age-matched healthy subjects.

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By definition, aging is a natural, gradual and continuous process. On the other hand, frailty reflects the increase in vulnerability to stressors and shortens the time without disease (health span) while longevity refers to the length of life (lifespan). The average life expectancy has significantly increased during the last few decades.

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Mobile technology (MT) has become essential in receiving information and services during the COVID-19 pandemic. Imposed quarantines could have led to varying adaptations of MT use. This study explored how COVID-19 impacted behavior, perception, and attitudes toward MT use in the United States.

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Sepsis is a global health challenge, with over 49 million cases annually. Recent medical advancements have increased in-hospital survival rates to approximately 80%, but the escalating incidence of sepsis, owing to an ageing population, rise in chronic diseases, and antibiotic resistance, have also increased the number of sepsis survivors. Subsequently, there is a growing prevalence of "post-sepsis syndrome" (PSS).

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Mechanical ventilation during cardiothoracic surgery is life-saving but can lead to ventilator-induced diaphragm dysfunction (VIDD) and prolong ventilator weaning and hospital length of stay. Intraoperative phrenic nerve stimulation may preserve diaphragm force production to offset VIDD; we also investigated changes in mitochondrial function after stimulation. During cardiothoracic surgeries ( = 21), supramaximal, unilateral phrenic nerve stimulation was performed every 30 min for 1 min.

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Altered mitochondrial quality and function in muscle may be involved in age-related physical function decline. The role played by the autophagy-lysosome system, a major component of mitochondrial quality control (MQC), is incompletely understood. This study was undertaken to obtain initial indications on the relationship between autophagy, mitophagy, and lysosomal markers in muscle and measures of physical performance and lower extremity tissue composition in young and older adults.

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Objectives: Individuals with prior cancer diagnosis are more likely to have low muscle mass (LMM) than their cancer-free counterparts. Understanding the effects of LMM on the prognosis of cancer survivors can be clinically important. The aim of this study was to investigate whether risks for all-cause and cardiovascular disease (CVD)-specific mortality differ by status of LMM in cancer survivors and a matched cohort without cancer history.

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Background: Sepsis-induced gut microbiome alterations contribute to sepsis-related morbidity and mortality. Given evidence for improved postsepsis outcomes in females compared with males, we hypothesized that female mice maintain microbiota resilience versus males.

Methods: Mixed-sex C57BL/6 mice underwent cecal ligation and puncture (CLP) with antibiotics, saline resuscitation, and daily chronic stress and were compared with naive (nonsepsis/no antibiotics) controls.

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Sepsis is currently defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The skeletal muscle system is among the host organ systems compromised by sepsis. The resulting neuromuscular dysfunction and impaired regenerative capacity defines sepsis-induced myopathy and manifests as atrophy, loss of strength, and hindered regeneration after injury.

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Spexin (SPX) is a 14-amino acid neuropeptide, discovered recently using bioinformatic techniques. It is encoded by the Ch12:orf39 gene that is widely expressed in different body tissues/organs across species, and secreted into systemic circulation. Recent reports have highlighted a potentially important regulatory role of SPX in obesity and related comorbidities.

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Sepsis survivors experience a persistent myopathy characterized by skeletal muscle weakness, atrophy, and an inability to repair/regenerate damaged or dysfunctional myofibers. The origins and mechanisms of this persistent sepsis-induced myopathy are likely complex and multifactorial. Nevertheless, the pathobiology is thought to be triggered by the interaction between circulating pathogens and impaired muscle metabolic status.

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Background: Hospital deaths after sepsis have decreased substantially and most young adult survivors rapidly recover (RAP). However, many older survivors develop chronic critical illness (CCI) with poor long-term outcomes. The etiology of CCI is multifactorial and the relative importance remains unclear.

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With the ever-expanding population of patients infected with SARS-CoV-2, we are learning more about the immediate and long-term clinical manifestations of coronavirus disease 2019 (COVID-19). Ischemic stroke (IS) is now one of the well-documented additional clinical manifestations of COVID-19. Most COVID-19 related IS cases have been categorized as cryptogenic or embolic stroke of undetermined source (ESUS), which are most often suspected to have an undiagnosed cardioembolic source.

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Aging-related changes to biological structures such as cardiovascular and musculoskeletal systems contribute to the development of comorbid conditions including cardiovascular disease and frailty, and ultimately lead to premature death. Although, frail older adults often demonstrate both cardiovascular and musculoskeletal comorbidities, the etiology of sarcopenia, and especially the contribution of cardiovascular aging is unclear. Aging-related vascular calcification is prevalent in older adults and is a known risk factor for cardiovascular disease and death.

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Mitochondrial dysfunction and iron (Fe) dyshomeostasis are invoked among the mechanisms contributing to muscle aging, possibly via a detrimental mitochondrial-iron feed-forward loop. We quantified the labile Fe pool, Fe isotopes, and the expression of mitochondrial Fe handling proteins in muscle biopsies obtained from young and older adults. The expression of key proteins of mitochondrial quality control (MQC) and the abundance of the mitochondrial DNA common deletion (mtDNA) were also assessed.

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