npj aging最新文献

Senescence and epigenetic alterations stand out as two well-characterized hallmarks of aging. When cells become senescent, they cease proliferation and release inflammatory molecules collectively termed the Senescence-Associated Secretory Phenotype (SASP). Senescence and SASP are implicated in numerous age-related diseases. Senescent cell nuclei undergo epigenetic reprogramming, which intricately regulates SASP expression. This review outlines the current understanding of how senescent cells undergo epigenetic changes and how these alterations govern SASP expression.

Age-related changes in oligodendrocyte precursor cells (OPCs) contribute to white matter dysfunction. In aged mice, we hypothesized that myelin-dense fimbria OPCs possess niche-specific properties, compared to hippocampal OPCs. Aged fimbria OPCs were fewer, larger, and localized to neighboring microglia. We identified age-increased p16/Cdkn2a-expressing OPCs enriched for senescence-related pathways and distinct senescence signatures between hippocampus and fimbria. Aged brain OPC populations differ in microenvironment properties and responses to senescence-directed intervention.

Cellular senescence has been implicated in many age-related pathologies including atherosclerosis, heart failure, age-related cardiac remodeling, diabetic cardiomyopathy and the metabolic syndrome. Here, we will review the characteristics of senescent cells and their endogenous regulators, and summarize the metabolic stressors that induce cell senescence. We will discuss the evidence of cell senescence in the onset and progression of several cardiometabolic diseases and the therapeutic potential of anti-senescence therapies.

The senescence phenotype is heterogeneous, as observed by the context-dependent differential expression of senescence markers. Here, we provide evidence to demonstrate an inverse relationship in the expression pattern of the two murine variants of p21 (p21v1, and p21v2) in aging and hemorrhagic shock. While an upregulation of p21v1 was observed following hemorrhagic shock injury, p21v2 was upregulated in the aged mouse. We further show that the p21v1 response is, at least, partially independent of p53.

Patients with diabetes mellitus (DM) are at risk of developing frailty, but studies rarely addressed risk factors for frailty worsening. We investigated whether blood pressure (BP)-lowering agents influenced such risk in these patients. Adults with type 2 DM were identified from National Taiwan University Hospital, with the primary outcome, the worsening of frailty by ≧1 score increase of FRAIL scale determined. We used the Cox proportional hazards analysis to derive the risk of worsening frailty associated with BP-lowering agents. Among 41,440 patients with DM, 27.4% developed worsening frailty after 4.09 years of follow-up. Cox regression revealed that diuretics (hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06-1.18) and α-blocker (HR 1.14, 95% CI 1.06-1.23) users had a significantly higher risk of worsening frailty than non-users, whereas the risk was lower among β-blocker users (HR 0.93, 95% CI 0.88-0.98). It would be therefore prudent to weigh the advantages and disadvantages of using specific BP-lowering agent classes.

The prevalence of sleep disorders has been reported from 1.6% to 56.0%, worldwide. Sleep deprivation causes cardiovascular diseases (CVDs) including atherosclerosis, vascular aging, hypertension, heart dysfunction, reduced heart rate variability, and cardiac arrhythmia. Reduced tissue oxygen causes various CVDs by activating pro-inflammatory factors and increasing oxidative stress. Sleep disorders are more important and prevalent in older people and cause more severe cardiovascular complications. On the other hand, the reduction of Klotho level, an age-dependent protein whose expression decreases with age, is associated with age-related diseases. Sirtuins, class III histone deacetylases, also are among the essential factors in postponing cellular aging and increasing the lifespan of organisms, and they do this by regulating different pathways in the cell. Sirtuins and Klotho play an important role in the pathophysiology of CVDS and both have anti-oxidative stress and anti-inflammatory activity. Studies have shown that the levels of Klotho and sirtuins are altered in sleep disorders. In this article, alterations of Klotho and sirtuins in sleep disorders and in the development of sleep-related CVDs were reviewed and the possible signaling pathways were discussed. The inclusion criteria were studies with keywords of different types of sleep disorders and CVDs, klotho, SIRT1-7, and sirtuins in PubMed, Scopus, Embase، Science Direct، Web of Sciences and Google Scholar by the end of 2023. The studies revealed there is a bidirectional relationship between sleep disorders and the serum and tissue levels of Klotho and sirtuins and sleep related-CVDs.

Prenatal adversity affects cognitive and brain aging. Both lipid and leptin concentrations may be involved. We investigated if prenatal undernutrition is associated with a specific blood lipid profile and/or leptin concentrations, and if these relate to cognitive function and brain aging. 801 plasma samples of members of the Dutch famine birth cohort were assessed for lipidomics and leptin at age 58. Cognitive performance was measured with a Stroop task at 58, and MRI-based BrainAGE was derived in a subsample at 68. Out of 259 lipid signals, a signature of five identified individuals who were undernourished prenatally. These five lipids were not associated with cognitive performance, but three were predictive of BrainAGE. Leptin was not associated with prenatal famine exposure, Stroop performance, or BrainAGE. In conclusion, prenatal undernutrition was associated with an altered lipid profile predictive of BrainAGE 10 years later, demonstrating the potential of lipid profiles as early biomarkers for accelerated brain aging.

Senescence is an anti-tumour mechanism and hallmark of cancer. Loss or mutation of key senescence effectors, such as p16INK4A, are frequently observed in cancer. Intriguingly, some human tumours are both proliferative and senescent-marker positive (Sen-Mark+). Here, we explore this paradox, focusing on the prognostic consequences and the current challenges in classifying these cells. We discuss future strategies for Sen-Mark+ cell detection together with emerging opportunities to exploit senescence for cancer.

Early detection of cognitive decline is essential for timely intervention and effective management of age-related impairments. We monitored repetitive reaction times to a simple task on senior-friendly tablet computers among 72 functionally independent older adults, with a mean age of 82, ranging up to 100 years, within natural settings over two years. Functional principal component analyses revealed a consistent decrease in reaction time in line with their task experience among those without subjective cognitive decline. Conversely, individuals reporting subjective cognitive decline showed no consistent trend and exhibited wide variability over time. These distinctive reaction time trajectories in very old adults suggest the potential for monitoring as a non-invasive, convenient method for early detection of cognitive impairment.

Heterochronic parabiosis consists of surgically connecting the circulatory systems of a young and an old animal. This technique serves as a model to study circulating factors that accelerate aging in young organisms exposed to old blood or induce rejuvenation in old organisms exposed to young blood. Despite the promising results, the exact cellular and molecular mechanisms remain unclear, so this study aims to explore and elucidate them in more detail.