Perspectives on Aging and Quality of Life

Healthcare, Journal Year: 2023, Volume and Issue: 11(15), P. 2131 - 2131

Published: July 26, 2023

The aging of the world's population and health problems accompanying it are becoming increasingly severe. Healthcare policies in developed countries focus on how to prevent treat diseases associated with maintain quality life. Typical age-related include deafness, cataracts, osteoarthritis, chronic obstructive pulmonary disease, diabetes mellitus, dementia. Although mechanisms by which these develop differ, they all caused accumulation molecular cellular damage over time. In addition, can cause a decline physical mental functions ability perform activities daily living, as well loss roles society sense fulfillment Therefore, there is need for treatment measures accurately grasp This review aims introduce areas representative papers expected be contributed special issue "Aging Quality Life".

Language: Английский

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High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 18, 2024

Abstract Telomeres are the protective nucleoprotein structures at end of linear eukaryotic chromosomes. Telomeres’ repetitive nature and length have traditionally challenged precise assessment composition individual human telomeres. Here, we present Telo-seq to resolve bulk, chromosome arm-specific allele-specific telomere lengths using Oxford Nanopore Technologies’ native long-read sequencing. resolves shortening in five population doubling increments reveals intrasample, arm-specific, heterogeneity. can reliably discriminate between telomerase- ALT-positive cancer cell lines. Thus, is a tool study biology during development, aging, unprecedented resolution.

Language: Английский

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Redox regulation: mechanisms, biology and therapeutic targets in diseases

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both onset progression of various diseases. Under physiological conditions, oxidative free radicals generated by mitochondrial respiratory chain, endoplasmic reticulum, NADPH oxidases can be effectively neutralized NRF2-mediated antioxidant responses. These responses elevate synthesis superoxide dismutase (SOD), catalase, well key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption this finely tuned equilibrium is closely linked to pathogenesis wide range Recent advances have broadened our understanding molecular mechanisms underpinning dysregulation, highlighting pivotal roles genomic instability, epigenetic modifications, protein degradation, metabolic reprogramming. findings provide foundation for exploring regulation mechanistic basis improving therapeutic strategies. While antioxidant-based therapies shown early promise conditions where stress plays primary pathological role, efficacy diseases characterized complex, multifactorial etiologies remains controversial. A deeper, context-specific signaling, particularly redox-sensitive proteins, designing targeted aimed at re-establishing balance. Emerging small molecule inhibitors that target specific cysteine residues proteins demonstrated promising preclinical outcomes, setting stage forthcoming clinical trials. In review, we summarize current intricate relationship disease also discuss how these insights leveraged optimize strategies practice.

Language: Английский

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Extracellular vesicles in tumor immunity: mechanisms and novel insights

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Feb. 14, 2025

Extracellular vesicles (EVs), nanoscale secreted by cells, have attracted considerable attention in recent years due to their role tumor immunomodulation. These facilitate intercellular communication transporting proteins, nucleic acids, and other biologically active substances, they exhibit a dual development immune evasion mechanisms. Specifically, EVs can assist cells evading surveillance attack impairing cell function or modulating immunosuppressive pathways, thereby promoting progression metastasis. Conversely, also transport release immunomodulatory factors that stimulate the activation regulation of system, enhancing body's capacity combat malignant diseases. This functionality presents promising avenues targets for immunotherapy. By examining biological characteristics influence on immunity, novel therapeutic strategies be developed improve efficacy relevance cancer treatment. review delineates complex immunomodulation explores potential implications approaches, aiming establish theoretical foundation provide practical insights advancement future EVs-based immunotherapy strategies.

Language: Английский

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Thymidine nucleotide metabolism controls human telomere length

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(4), P. 568 - 580

Published: March 23, 2023

Language: Английский

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Digital telomere measurement by long-read sequencing distinguishes healthy aging from disease

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 18, 2024

Abstract Telomere length is an important biomarker of organismal aging and cellular replicative potential, but existing measurement methods are limited in resolution accuracy. Here, we deploy digital telomere (DTM) by nanopore sequencing to understand how distributions human change with age disease. We measure attrition de novo elongation up 30 bp genetically defined populations cells, blood cells from healthy donors patients genetic defects maintenance. find that accompanied a progressive loss long telomeres accumulation shorter telomeres. In maintenance, the short more pronounced correlates phenotypic severity. apply machine learning train binary classification model distinguishes individuals those biology disorders. This bioinformatic pipeline will advance our understanding maintenance mechanisms use as clinical

Language: Английский

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Genetic architecture of telomere length in 462,666 UK Biobank whole-genome sequences

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(9), P. 1832 - 1840

Published: Aug. 27, 2024

Telomeres protect chromosome ends from damage and their length is linked with human disease aging. We developed a joint telomere metric, combining quantitative PCR whole-genome sequencing measurements 462,666 UK Biobank participants. This metric increased SNP heritability, suggesting that it better captures genetic regulation of length. Exome-wide rare-variant gene-level collapsing association studies identified 64 variants 30 genes significantly associated length, including allelic series in ACD RTEL1. Notably, 16% these are known drivers clonal hematopoiesis-an age-related somatic mosaicism myeloid cancers several nonmalignant diseases. Somatic variant analyses revealed gene-specific associations lengthened telomeres individuals large SRSF2-mutant clones, compared shortened expansions driven by other genes. Collectively, our findings demonstrate the impact rare on larger effects observed among also hematopoiesis.

Language: Английский

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Systemic aging fuels heart failure: Molecular mechanisms and therapeutic avenues

ESC Heart Failure, Journal Year: 2024, Volume and Issue: unknown

Published: July 22, 2024

Abstract Systemic aging influences various physiological processes and contributes to structural functional decline in cardiac tissue. These alterations include an increased incidence of left ventricular hypertrophy, a diastolic function, atrial dilation, fibrillation, myocardial fibrosis amyloidosis, elevating susceptibility chronic heart failure (HF) the elderly. Age‐related dysfunction stems from prolonged exposure genomic, epigenetic, oxidative, autophagic, inflammatory regenerative stresses, along with accumulation senescent cells. Concurrently, age‐related changes vascular system, attributed endothelial dysfunction, arterial stiffness, impaired angiogenesis, oxidative stress inflammation, impose additional strain on heart. Dysregulated mechanosignalling nitric oxide signalling play critical roles associated HF. Metabolic drives intricate shifts glucose lipid metabolism, leading insulin resistance, mitochondrial within cardiomyocytes. contribute contractility, ultimately propelling low‐grade conjunction senescence‐associated secretory phenotype, aggravates age by promoting immune cell infiltration into myocardium, fostering This is further exacerbated comorbidities like coronary artery disease (CAD), atherosclerosis, hypertension, obesity, diabetes kidney (CKD). CAD atherosclerosis induce ischaemia adverse remodelling, while hypertension hypertrophy fibrosis. Obesity‐associated inflammation dyslipidaemia create profibrotic environment, whereas diabetes‐related metabolic disturbances impair function. CKD‐related fluid overload, electrolyte imbalances uraemic toxins exacerbate HF through systemic neurohormonal renin‐angiotensin‐aldosterone system (RAAS) activation. Recognizing as modifiable process has opened avenues target both lifestyle interventions therapeutics. Exercise, known for its antioxidant effects, can partly reverse pathological remodelling elderly countering linked HF, such senescence declining cardiomyocyte regeneration. Dietary plant‐based ketogenic diets, caloric restriction macronutrient supplementation are instrumental maintaining energy balance, reducing adiposity addressing micronutrient Therapeutic advancements targeting underway. Key approaches senomorphics senolytics limit senescence, antioxidants stress, anti‐inflammatory drugs interleukin (IL)‐1β inhibitors, rejuvenators nicotinamide riboside, resveratrol sirtuin (SIRT) activators autophagy enhancers metformin sodium‐glucose cotransporter 2 (SGLT2) all which offer potential preserving function alleviating burden.

Language: Английский

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Inherited Bone Marrow Failure Syndromes

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 51 - 94

Published: Jan. 1, 2024

Language: Английский

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Human Oncostatin M deficiency underlies an inherited severe bone marrow failure syndrome

Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Oncostatin M (OSM) is a cytokine with the unique ability to interact both OSM receptor (OSMR) and leukemia inhibitory factor (LIFR). On other hand, OSMR interacts IL31RA form interleukin-31 receptor. This intricate network of cytokines receptors makes it difficult understand specific function OSM. While monoallelic loss-of-function (LoF) mutations in underlie autosomal dominant familial primary localized cutaneous amyloidosis, vivo consequences human deficiency have never been reported so far. Here, we identified three young individuals from consanguineous family presenting inherited severe bone marrow failure syndromes (IBMFS) characterized by profound anemia, thrombocytopenia, neutropenia. Genetic analysis revealed homozygous one base-pair insertion sequence associated disease. Structural functional analyses showed that this variant causes frameshift replaces C-terminal portion OSM, which contains FxxK motif LIFR, neopeptide. The lack detection signaling mutant suggests LoF mutation. Analysis zebrafish models further supported role OSM/OSMR erythroid progenitor proliferation neutrophil differentiation. Our study provides previously uncharacterized unexpectedly limited consequence humans.

Language: Английский

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