Disruption of PCSK9 Suppresses Inflammation and Attenuates Abdominal Aortic Aneurysm Formation.

Background: Abdominal aortic aneurysm (AAA) is a chronic vascular inflammatory disease without effective medications. PCSK9 (proprotein convertase subtilisin/kexin 9), a serine protease from the proprotein convertase family, has recently been associated with AAA in human genome-wide association studies. However, its role in AAA is unknown.

Enhancing homology-directed repair efficiency with HDR-boosting modular ssDNA donor.

Despite the potential of small molecules and recombinant proteins to enhance the efficiency of homology-directed repair (HDR), single-stranded DNA (ssDNA) donors, as currently designed and chemically modified, remain suboptimal for precise gene editing. Here, we screen the biased ssDNA binding sequences of DNA repair-related proteins and engineer RAD51-preferred sequences into HDR-boosting modules for ssDNA donors. Donors with these modules exhibit an augmented affinity for RAD51, thereby enhancing HDR efficiency across various genomic loci and cell types when cooperated with Cas9, nCas9, and Cas12a.

Therapeutic potential of alternative splicing in cardiovascular diseases.

RNA splicing is an important RNA processing step required by multiexon protein-coding mRNAs and some noncoding RNAs. Precise RNA splicing is required for maintaining gene and cell function; however, mis-spliced RNA transcripts can lead to loss- or gain-of-function effects in human diseases. Mis-spliced RNAs induced by gene mutations or the dysregulation of splicing regulators may result in frameshifts, nonsense-mediated decay (NMD), or inclusion/exclusion of exons.

What we talk about when we talk about spinal cord aging.

Spinal cord-associated disorders are common in the elderly population; however, the mechanisms underlying spinal aging remain elusive. In a recent Nature paper, Sun et al. systemically analyzed aged spines in nonhuman primates and identified a new cluster of CHIT1-positive microglia that drives motor neuron senescence and subsequent spine aging.

[Study of senescence protein p66 on myocardial tissue repair in adult mice].

Our previous study has shown that p66 plays an important role in the process of myocardial regeneration in newborn mice, and p66 deficiency leads to weakened myocardial regeneration in newborn mice. This study aims to explore the role of p66 protein in myocardial injury repair after myocardial infarction in adult mice, in order to provide a new target for the treatment of myocardial injury after myocardial infarction. Mouse myocardial infarction models of adult wild-type (WT) and p66 knockout (KO) were constructed by anterior descending branch ligation.

A biomarker framework for cardiac aging: the Aging Biomarker Consortium consensus statement.

Cardiac aging constitutes a significant risk factor for cardiovascular diseases prevalent among the elderly population. Urgent attention is required to prioritize preventive and management strategies for age-related cardiovascular conditions to safeguard the well-being of elderly individuals. In response to this critical challenge, the Aging Biomarker Consortium (ABC) of China has formulated an expert consensus on cardiac aging biomarkers.

SIRT6 is an epigenetic repressor of thoracic aortic aneurysms via inhibiting inflammation and senescence.

Thoracic aortic aneurysms (TAAs) develop asymptomatically and are characterized by dilatation of the aorta. This is considered a life-threating vascular disease due to the risk of aortic rupture and without effective treatments. The current understanding of the pathogenesis of TAA is still limited, especially for sporadic TAAs without known genetic mutation.

Sirtuin 2 deficiency aggravates ageing-induced vascular remodelling in humans and mice.

Aims: The mechanisms underlying ageing-induced vascular remodelling remain unclear. This study investigates the role and underlying mechanisms of the cytoplasmic deacetylase sirtuin 2 (SIRT2) in ageing-induced vascular remodelling.

Methods And Results: Transcriptome and quantitative real-time PCR data were used to analyse sirtuin expression.

Lysine crotonylation of SERCA2a correlates to cardiac dysfunction and arrhythmia in Sirt1 cardiac-specific knockout mice.

Protein post-translational modifications (PTMs) are important regulators of protein functions and produce proteome complexity. SIRT1 has NAD-dependent deacylation of acyl-lysine residues. The present study aimed to explore the correlation between lysine crotonylation (Kcr) on cardiac function and rhythm in Sirt1 cardiac-specific knockout (ScKO) mice and related mechanism.

Biomarkers of aging.

Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need.

Mic60 is essential to maintain mitochondrial integrity and to prevent encephalomyopathy.

Mitochondrial encephalomyopathies (ME) are frequently associated with mutations of mitochondrial DNA, but the pathogenesis of a subset of ME (sME) remains elusive. Here we report that haploinsufficiency of a mitochondrial inner membrane protein, Mic60, causes progressive neurological abnormalities with insulted mitochondrial structure and neuronal loss in mice. In addition, haploinsufficiency of Mic60 reduces mitochondrial membrane potential and cellular ATP production, increases reactive oxygen species, and alters mitochondrial oxidative phosphorylation complexes in neurons in an age-dependent manner.

Single-cell analyses highlight the proinflammatory contribution of C1q-high monocytes to Behçet's disease.

Behçet's disease (BD) is a chronic vasculitis characterized by systemic immune aberrations. However, a comprehensive understanding of immune disturbances in BD and how they contribute to BD pathogenesis is lacking. Here, we performed single-cell and bulk RNA sequencing to profile peripheral blood mononuclear cells (PBMCs) and isolated monocytes from BD patients and healthy donors.

Comprehensive assessment of cellular senescence in the tumor microenvironment.

Cellular senescence (CS), a state of permanent growth arrest, is intertwined with tumorigenesis. Due to the absence of specific markers, characterizing senescence levels and senescence-related phenotypes across cancer types remain unexplored. Here, we defined computational metrics of senescence levels as CS scores to delineate CS landscape across 33 cancer types and 29 normal tissues and explored CS-associated phenotypes by integrating multiplatform data from ~20 000 patients and ~212 000 single-cell profiles.

Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing.

The age-dependent decline in remyelination potential of the central nervous system during ageing is associated with a declined differentiation capacity of oligodendrocyte progenitor cells (OPCs). The molecular players that can enhance OPC differentiation or rejuvenate OPCs are unclear. Here we show that, in mouse OPCs, nuclear entry of SIRT2 is impaired and NAD levels are reduced during ageing.

Targeting senescent cells for vascular aging and related diseases.

Cardiovascular diseases are a serious threat to human health, especially in the elderly. Vascular aging makes people more susceptible to cardiovascular diseases due to significant dysfunction or senescence of vascular cells and maladaptation of vascular structure and function; moreover, vascular aging is currently viewed as a modifiable cardiovascular risk factor. To emphasize the relationship between senescent cells and vascular aging, we first summarize the roles of senescent vascular cells (endothelial cells, smooth muscle cells and immune cells) in the vascular aging process and inducers that contribute to cellular senescence.

Histone Deacetylase SIRT1, Smooth Muscle Cell Function, and Vascular Diseases.

Vascular smooth muscle cells (VSMCs), located in the media of artery, play key roles in maintaining the normal vascular physiological functions. Abnormality in VSMCs is implicated in vascular diseases (VDs), including atherosclerosis, abdominal aortic aneurysm (AAA), aortic dissection, and hypertension by regulating the process of inflammation, phenotypic switching, and extracellular matrix degradation. Sirtuins (SIRTs), a family of proteins containing seven members (from SIRT1 to SIRT7) in mammals, function as NAD-dependent histone deacetylases and ADP-ribosyltransferases.

A research agenda for ageing in China in the 21st century (2nd edition): Focusing on basic and translational research, long-term care, policy and social networks.

One of the key issues facing public healthcare is the global trend of an increasingly ageing society which continues to present policy makers and caregivers with formidable healthcare and socio-economic challenges. Ageing is the primary contributor to a broad spectrum of chronic disorders all associated with a lower quality of life in the elderly. In 2019, the Chinese population constituted 18 % of the world population, with 164.

Metabolic regulation of immune cells in proinflammatory microenvironments and diseases during ageing.

The process of ageing includes molecular changes within cells and interactions between cells, eventually resulting in age-related diseases. Although various cells (immune cells, parenchymal cells, fibroblasts and endothelial cells) in tissues secrete proinflammatory signals in age-related diseases, immune cells are the major contributors to inflammation. Many studies have emphasized the role of metabolic dysregulation in parenchymal cells in age-related inflammatory diseases.

Global Lysine Crotonylation Profiling of Mouse Liver.

Lysine crotonylation (Kcr) is a recently discovered post-translational modification that potentially regulates multiple biological processes. With an objective to expand the available crotonylation datasets, LC-MS/MS is performed using mouse liver samples under normal physiological conditions to obtain in vivo crotonylome. A label-free strategy is used and 10 034 Class I (localization probabilities > 0.

Cardiomyocyte Senescence and Cellular Communications Within Myocardial Microenvironments.

Cardiovascular diseases have become the leading cause of human death. Aging is an independent risk factor for cardiovascular diseases. Cardiac aging is associated with maladaptation of cellular metabolism, dysfunction (or senescence) of cardiomyocytes, a decrease in angiogenesis, and an increase in tissue scarring (fibrosis).