Telomere dysfunction in ageing and age-related diseases

Nature Cell Biology, Год журнала: 2022, Номер 24(2), С. 135 - 147

Опубликована: Фев. 1, 2022

Язык: Английский

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Somatic mutation rates scale with lifespan across mammals

Nature, Год журнала: 2022, Номер 604(7906), С. 517 - 524

Опубликована: Апрель 13, 2022

Abstract The rates and patterns of somatic mutation in normal tissues are largely unknown outside humans 1–7 . Comparative analyses can shed light on the diversity mutagenesis across species, long-standing hypotheses about evolution their role cancer ageing. Here we performed whole-genome sequencing 208 intestinal crypts from 56 individuals to study landscape 16 mammalian species. We found that was dominated by seemingly endogenous mutational processes all including 5-methylcytosine deamination oxidative damage. With some differences, signatures other species resembled those described 8 , although relative contribution each signature varied Notably, rate per year greatly exhibited a strong inverse relationship with lifespan, no life-history trait studied showing comparable association. Despite widely different life histories among examined—including variation around 30-fold lifespan 40,000-fold body mass—the burden at end only factor 3. These data unveil common mammals, suggest evolutionarily constrained may be contributing

Язык: Английский

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Atrial fibrillation

Nature Reviews Disease Primers, Год журнала: 2022, Номер 8(1)

Опубликована: Апрель 7, 2022

Atrial fibrillation (AF) is the most common cardiac arrhythmia despite substantial efforts to understand pathophysiology of condition and develop improved treatments. Identifying underlying causative mechanisms AF in individual patients difficult efficacy current therapies suboptimal. Consequently, incidence steadily rising there a pressing need for novel therapies. Research has revealed that defects specific molecular pathways underlie pathogenesis, resulting electrical conduction disorders drive AF. The severity this so-called electropathology correlates with stage disease progression determines response treatment. Therefore, unravelling expected fuel development innovative personalized diagnostic tools mechanism-based Moreover, co-creation studies implement prerequisite successful management. Currently, various treatment modalities targeting AF-related electropathology, including lifestyle changes, pharmaceutical nutraceutical therapy, substrate-based ablative neuromodulation, are available maintain sinus rhythm might offer holistic strategy treat increasing prevalence as populations age. This Primer provides an overview epidemiology, AF, approaches treatments, highlights important directions improve understanding management patients.

Язык: Английский

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Meta-hallmarks of aging and cancer

Cell Metabolism, Год журнала: 2023, Номер 35(1), С. 12 - 35

Опубликована: Янв. 1, 2023

Язык: Английский

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Chemotherapy Side-Effects: Not All DNA Damage Is Equal

Cancers, Год журнала: 2022, Номер 14(3), С. 627 - 627

Опубликована: Янв. 26, 2022

Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment later in life they are frequently confronted with the severe negative side-effects their life-saving treatment. The occurrence numerous features accelerated aging, seriously affecting quality life, has now become one most pressing problems associated (pediatric) Chemotherapies target damage DNA, causing mutations or genome instability, a major hallmark both aging. there types chemotherapeutic drugs that genotoxic interfere DNA metabolism different ways, each own biodistribution, kinetics, biological fate. Depending on type lesion produced (e.g., interference replication RNA transcription), organ cell inflicted cycle differentiation status, metabolic state, activity clearance detoxification mechanisms, cellular condition micro-environment), degree exposure, outcomes can largely differ. These considerations provide conceptual framework which classes chemotherapeutics contribute development toxicities aging systems. Here, we summarize observed ex-cancer patients discuss might be responsible.

Язык: Английский

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The landscape of aging

Science China Life Sciences, Год журнала: 2022, Номер 65(12), С. 2354 - 2454

Опубликована: Сен. 2, 2022

Язык: Английский

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Making sense of the ageing methylome

Nature Reviews Genetics, Год журнала: 2022, Номер 23(10), С. 585 - 605

Опубликована: Май 2, 2022

Язык: Английский

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The p53 network: cellular and systemic DNA damage responses in cancer and aging

Trends in Genetics, Год журнала: 2022, Номер 38(6), С. 598 - 612

Опубликована: Март 25, 2022

Язык: Английский

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From imbalance to impairment: the central role of reactive oxygen species in oxidative stress-induced disorders and therapeutic exploration

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Окт. 18, 2023

Increased production and buildup of reactive oxygen species (ROS) can lead to various health issues, including metabolic problems, cancers, neurological conditions. Our bodies counteract ROS with biological antioxidants such as SOD, CAT, GPx, which help prevent cellular damage. However, if there is an imbalance between these antioxidants, it result in oxidative stress. This cause genetic epigenetic changes at the molecular level. review delves into how plays a role disorders caused by We also look animal models used for researching pathways. study offers insights mechanism, pathology, changes, assist drug development disease understanding.

Язык: Английский

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Connecting aging biology and inflammation in the omics era

Journal of Clinical Investigation, Год журнала: 2022, Номер 132(14)

Опубликована: Июль 14, 2022

Aging is characterized by the accumulation of damage to macromolecules and cell architecture that triggers a proinflammatory state in blood solid tissues, termed inflammaging. Inflammaging has been implicated pathogenesis many age-associated chronic diseases as well loss physical cognitive function. The search for mechanisms underlie inflammaging focused initially on hallmarks aging, but it rapidly expanding multiple directions. Here, we discuss threads connecting cellular senescence mitochondrial dysfunction impaired mitophagy DNA damage, which may act hub We explore emerging multi-omics efforts aspire define complexity - identify molecular signatures novel targets interventions aimed at counteracting excessive inflammation its deleterious consequences while preserving physiological immune response. Finally, review evidence involved brain aging neurodegenerative diseases. Our goal broaden research agenda with an eye new therapeutic opportunities.

Язык: Английский

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