A5014342029- Telomeres, Telomerase, and Senescence
- Nutrition and Health in Aging
- Adipose Tissue and Metabolism
- Muscle Physiology and Disorders
- Genetics, Aging, and Longevity in Model Organisms
- Frailty in Older Adults
- Adipokines, Inflammation, and Metabolic Diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Muscle metabolism and nutrition
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- GDF15 and Related Biomarkers
- Diet and metabolism studies
- Circadian rhythm and melatonin
- Mitochondrial Function and Pathology
- Immune cells in cancer
- Metabolism, Diabetes, and Cancer
- Cerebral Palsy and Movement Disorders
- Single-cell and spatial transcriptomics
- MicroRNA in disease regulation
- Peroxisome Proliferator-Activated Receptors
- Neuroinflammation and Neurodegeneration Mechanisms
- Resilience and Mental Health
- Hormonal and reproductive studies
- Balance, Gait, and Falls Prevention
- Mesenchymal stem cell research
Mayo Clinic
2016-2025
Mayo Clinic in Arizona
2016-2025
Mayo Clinic in Florida
2016-2025
WinnMed
2014-2025
University of Leicester
2021
COPD Foundation
2021
Pain and Rehabilitation Medicine
2009-2020
Individual Differences
2020
John Wiley & Sons (United States)
2016
Hudson Institute
2016
The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene. Achieving the same small molecules would have tremendous impact on quality life and burden age-related chronic diseases. Here, we describe rationale for identification validation new class drugs termed senolytics, which selectively kill cells. By transcript analysis, discovered increased expression pro-survival networks in cells, consistent with their established resistance to apoptosis. Using...
Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety efficacy of testosterone treatment men who have limitations mobility not studied.
Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by interstitial remodelling, leading to compromised lung function. Cellular senescence markers are detectable within IPF tissue and senescent cell deletion rejuvenates health in aged mice. Whether how cells regulate or if their removal may be an efficacious intervention strategy unknown. Here we demonstrate elevated abundance of biomarkers lung, with p16 expression increasing severity. We show that the secretome...
Senescent cells, which can release factors that cause inflammation and dysfunction, the senescence-associated secretory phenotype (SASP), accumulate with ageing at etiological sites in multiple chronic diseases. Senolytics, including combination of Dasatinib Quercetin (D + Q), selectively eliminate senescent cells by transiently disabling pro-survival networks defend them against their own apoptotic environment. In first clinical trial senolytics, D Q improved physical function patients...
BackgroundCellular senescence is a key mechanism that drives age-related diseases, but has yet to be targeted therapeutically in humans. Idiopathic pulmonary fibrosis (IPF) progressive, fatal cellular senescence-associated disease. Selectively ablating senescent cells using dasatinib plus quercetin (DQ) alleviates IPF-related dysfunction bleomycin-administered mice.MethodsA two-center, open-label study of intermittent DQ (D:100 mg/day, Q:1250 three-days/week over three-weeks) was conducted...
Significance A hallmark of aging is chronic sterile inflammation, which closely associated with frailty and age-related diseases. We found that senescent fat progenitor cells accumulate in adipose tissue acquire a senescence-associated secretory phenotype (SASP), increased production proinflammatory cytokines compared nonsenescent cells. These provoked inflammation induced macrophage migration. The JAK pathway activated aging, the SASP can be suppressed by inhibiting JAK1/2 inhibitors...
The transcriptional coactivator peroxisome proliferator-activated receptor gamma 1alpha (PGC-1alpha) is a key integrator of neuromuscular activity in skeletal muscle. Ectopic expression PGC-1alpha muscle results increased mitochondrial number and function as well an increase oxidative, fatigue-resistant fibers. Whole body knock-out mice have very complex phenotype but do not marked phenotype. We thus analyzed muscle-specific to identify specific role for function. These exhibit shift from...
Senescent cells accumulate in fat with aging. We previously found genetic clearance of senescent from progeroid INK-ATTAC mice prevents lipodystrophy. Here we show that primary human progenitors secrete activin A and directly inhibit adipogenesis non-senescent progenitors. Blocking partially restored lipid accumulation expression key adipogenic markers differentiating exposed to cells. Mouse tissue increased Clearing 18-month-old naturally-aged reduced circulating A, blunted loss, enhanced...
Adipose tissue inflammation and dysfunction are associated with obesity-related insulin resistance diabetes, but mechanisms underlying this relationship unclear. Although senescent cells accumulate in adipose of obese humans rodents, a direct pathogenic role for these the development diabetes remains to be demonstrated. Here, we show that reducing cell burden mice, either by activating drug-inducible "suicide" genes driven p16
ABSTRACT Cellular senescence is a fundamental mechanism by which cells remain metabolically active yet cease dividing and undergo distinct phenotypic alterations, including upregulation of p16Ink4a, profound secretome changes, telomere shortening, decondensation pericentromeric satellite DNA. Because senescent accumulate in multiple tissues with aging, these the dysfunctional factors they secrete, termed senescence-associated secretory phenotype (SASP), are increasingly recognized as...
Although cellular senescence drives multiple age-related co-morbidities through the senescence-associated secretory phenotype, in vivo senescent cell identification remains challenging. Here, we generate a gene set (SenMayo) and validate its enrichment bone biopsies from two aged human cohorts. We further demonstrate reductions SenMayo following genetic clearance of cells mice adipose tissue humans pharmacological clearance. next use to identify hematopoietic or mesenchymal at single level...
OBJECTIVES: Peak power declines more precipitously than strength with advancing age and is a reliable measure of impairment strong predictor functional performance. We tested the hypothesis that high‐velocity resistance‐training program (HI) would increase muscle traditional low‐velocity (LO).
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Abstract Cellular senescence is characterized by an irreversible cell cycle arrest and a pro‐inflammatory senescence‐associated secretory phenotype (SASP), which major contributor to aging age‐related diseases. Clearance of senescent cells has been shown improve brain function in mouse models neurodegenerative However, it still unknown whether clearance alleviates cognitive dysfunction during the process. To investigate this, we first conducted single‐nuclei single‐cell RNA‐seq hippocampus...
Produced by senescent cells, the senescence-associated secretory phenotype (SASP) is a potential driver of age-related dysfunction. We tested whether circulating concentrations SASP proteins reflect age and medical risk in humans. first screened endothelial fibroblasts, preadipocytes, epithelial myoblasts to identify candidates for human profiling. then associations between clinical data from individuals throughout life span older adults undergoing surgery prevalent but distinct diseases. A...
Abstract Senescent cells drive age-related tissue dysfunction partially through the induction of a chronic senescence-associated secretory phenotype (SASP) 1 . Mitochondria are major regulators SASP; however, underlying mechanisms have not been elucidated 2 often essential for apoptosis, cell fate distinct from cellular senescence. During widespread mitochondrial outer membrane permeabilization (MOMP) commits to die 3 Here we find that MOMP occurring in subset mitochondria is feature This...
The COVID-19 pandemic has revealed the pronounced vulnerability of elderly and chronically ill to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced morbidity mortality. Cellular senescence contributes inflammation, multiple chronic diseases, age-related dysfunction, but effects on responses viral infection are unclear. Here, we demonstrate that senescent cells (SnCs) become hyper-inflammatory in response pathogen-associated molecular patterns (PAMPs), including SARS-CoV-2...