Hallmarks of aging: An expanding universe

Cell, Год журнала: 2023, Номер 186(2), С. 243 - 278

Опубликована: Янв. 1, 2023

Язык: Английский

---

Why does COVID-19 disproportionately affect older people?

Aging, Год журнала: 2020, Номер 12(10), С. 9959 - 9981

Опубликована: Май 29, 2020

The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient's age. Adults over 65 years age represent 80% hospitalizations have 23-fold greater risk death than those under 65. In the clinic, COVID-19 patients most commonly present with fever, cough dyspnea, from there can progress to acute respiratory distress syndrome, lung consolidation, cytokine release endotheliitis, coagulopathy, multiple organ failure death. Comorbidities such as cardiovascular disease, diabetes obesity increase chances fatal but they alone do not explain why is an independent factor. Here, we molecular differences between young, middle-aged older people that may mild illness in some life-threatening others. We also discuss several biological clocks could be used conjunction genetic tests identify both mechanisms individuals at risk. Finally, based these mechanisms, treatments survival people, simply by inhibiting virus, restoring patients' ability clear infection effectively regulate immune responses.

Язык: Английский

---

The central role of DNA damage in the ageing process

Nature, Год журнала: 2021, Номер 592(7856), С. 695 - 703

Опубликована: Апрель 28, 2021

Язык: Английский

---

Loss of epigenetic information as a cause of mammalian aging

Cell, Год журнала: 2023, Номер 186(2), С. 305 - 326.e27

Опубликована: Янв. 1, 2023

Язык: Английский

---

The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy

Frontiers in Cell and Developmental Biology, Год журнала: 2020, Номер 8

Опубликована: Сен. 29, 2020

Genetic mutations and abnormal gene regulation are key mechanisms underlying tumorigenesis. Nucleosomes, which consist of DNA wrapped around histone cores, represent the basic units chromatin. The fifth amino group (Nε) lysine residues is a common site for post-translational modifications (PTMs), these, acetylation second most common. Histone modulated by acetyltransferases (HATs) deacetylases (HDACs), involved in expression. Over past two decades, numerous studies characterizing HDACs HDAC inhibitors (HDACi) have provided novel exciting insights concerning their biological potential anti-cancer treatments. In this review, we detail diverse structures functions, including transcriptional regulation, metabolism, angiogenesis, damage response, cell cycle, apoptosis, protein degradation, immunity other several physiological processes. We also highlight avenues to use HDACi as novel, precision cancer

Язык: Английский

---

The landscape of aging

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

Опубликована: Сен. 2, 2022

Язык: Английский

---

DNA damage and repair in age-related inflammation

Nature reviews. Immunology, Год журнала: 2022, Номер 23(2), С. 75 - 89

Опубликована: Июль 13, 2022

Язык: Английский

---

DNA damage—how and why we age?

eLife, Год журнала: 2021, Номер 10

Опубликована: Янв. 29, 2021

Aging is a complex process that results in loss of the ability to reattain homeostasis following stress, leading, thereby, increased risk morbidity and mortality. Many factors contribute aging, such as time-dependent accumulation macromolecular damage, including DNA damage. The integrity nuclear genome essential for cellular, tissue, organismal health. damage constant threat because nucleic acids are chemically unstable under physiological conditions vulnerable attack by endogenous environmental factors. To combat this, all organisms possess highly conserved mechanisms detect repair Persistent (genotoxic stress) triggers signaling cascades drive cells into apoptosis or senescence avoid replicating damaged genome. drawback these cancer avoidance promote aging. Here, we review evidence plays causal role We also provide genotoxic stress linked other cellular processes implicated drivers mitochondrial metabolic dysfunction, altered proteostasis inflammation. These links between genetic code pillars aging support notion could be root

Язык: Английский

---

SIRT6 Protects Smooth Muscle Cells From Senescence and Reduces Atherosclerosis

Circulation Research, Год журнала: 2020, Номер 128(4), С. 474 - 491

Опубликована: Дек. 23, 2020

Rationale: Vascular smooth muscle cell (VSMC) senescence promotes atherosclerosis and features of plaque instability, in part, through lipid-mediated oxidative DNA damage telomere dysfunction. SIRT6 (Sirtuin 6) is a nuclear deacetylase involved response signaling, inflammation, metabolism; however, its role regulating VSMC unclear. Objective: We examined expression human VSMCs, the role, regulation, downstream pathways activated by SIRT6, how regulates atherogenesis. Methods Results: protein, but not mRNA, was markedly reduced VSMCs mouse atherosclerotic plaques, derived from plaques or undergoing replicative palmitate-induced versus healthy aortic VSMCs. The ubiquitin ligase CHIP (C terminus HSC70-interacting protein) promoted stability, palmitate p38- c-Jun N-terminal kinase-dependent manner. bound to telomeres, while inhibition using shRNA deacetylase-inactive mutant (SIRT6 H133Y ) shortened lifespan induced senescence, associated with telomeric H3K9 (histone H3 lysine 9) hyperacetylation 53BP1 (p53 binding protein 1) binding, indicative damage. In contrast, overexpression preserved integrity, delayed cellular inflammatory cytokine changes metabolism senescence. , proliferation prevented senescence-associated metabolic changes. ApoE −/− (apolipoprotein E) mice were generated that overexpress only. SM22α-hSIRT6/ApoE had atherosclerosis, markers inflammation compared littermate controls, SM22α-hSIRT6 /ApoE showed increased instability. Conclusions: positively regulated CHIP. maintenance inhibits atherogenesis, all dependent on activity. Our data show endogenous an important unrecognized inhibitor atherosclerosis.

Язык: Английский

---

Melatonin attenuates diabetic cardiomyopathy and reduces myocardial vulnerability to ischemia‐reperfusion injury by improving mitochondrial quality control: Role of SIRT6

Journal of Pineal Research, Год журнала: 2020, Номер 70(1)

Опубликована: Окт. 5, 2020

Abstract Targeting mitochondrial quality control with melatonin has been found promising for attenuating diabetic cardiomyopathy (DCM), although the underlying mechanisms remain largely undefined. Activation of SIRT6 and membrane receptors exerts cardioprotective effects while little is known about their roles during DCM. Using high‐fat diet‐streptozotocin‐induced rat model, we that prolonged diabetes significantly decreased nocturnal circulatory heart levels, reduced expressions cardiac receptors, myocardial AMPK‐PGC‐1α‐AKT signaling. 16 weeks treatment inhibited progression DCM following ischemia‐reperfusion (MI/R) injury by reducing fission, enhancing biogenesis mitophagy via re‐activating After induction diabetes, adeno‐associated virus carrying SIRT6‐specific small hairpin RNA or luzindole was delivered to animals. We showed knockdown antagonizing abolished protective against dysfunction as evidenced aggravated fission mitophagy. Additionally, shRNA melatonin‐induced activation well its actions. Collectively, demonstrated long‐term attenuated vulnerability MI/R through preserving control. Melatonin receptor‐mediated SIRT6‐AMPK‐PGC‐1α‐AKT axis played a key role in this process. may be strategy patients.

Язык: Английский

---