Aggregator

Within neurons, the misfolding and aggregation of certain proteins has been identified as a common feature of many late-onset neurodegenerative diseases (NDs). These aggregate-prone proteins include tau (in both primary tauopathies and in Alzheimer's disease) and alpha-synuclein in Parkinson's disease. There is strong experimental evidence that the upregulation of intracellular clearance pathways (autophagy and ubiquitin-proteasome pathways) can clear aggregate-prone proteins in experimental...

Parkinson's disease (PD) is a chronic neurological disorder characterized by loss of body movement control due to dopamine abnormalities. PD leads to various pathological symptoms, including muscle stiffness, bradykinesia, tremors, and postural disturbances. As a severe disease, PD caused approximately 329,000 deaths worldwide in 2019. However, PD treatment is very challenging; thus, alternative therapeutic strategies are in high demand. The primary therapeutic hurdle in PD therapy is the...

Parkinson's Disease (PD) is a neurodegenerative disorder primarily characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to classical motor symptoms such as tremors, rigidity, and bradykinesia. In later stages, patients frequently develop non-classical symptoms, including respiratory dysfunctions, which may result from neurodegeneration in brainstem regions involved in respiratory control, such as the pre-Bötzinger Complex (preBötC) and the retrotrapezoid...

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Frailty increasingly is recognized as a factor that modifies the relationship between disease biomarkers, including neuropathology, and dementia expression. The mechanisms underlying the relationship between frailty and dementia remain unclear, but blood biomarkers can offer insight into these mechanisms. We completed a scoping review of research examining the associations between blood biomarkers, frailty, and cognition. Three online databases were searched to identify original research...

Genome regulation is shaped not only by DNA sequence but also by epigenetic mechanisms that influence chromatin structure and gene expression. While epigenetics has classically focused on heritable DNA and histone modifications, growing evidence indicates that certain forms of DNA damage can also generate persistent changes in transcriptional states that are heritable in some scenarios. This review examines how diverse DNA damage-associated processes-including oxidative lesions, R-loops,...

CONCLUSIONS AND IMPLICATIONS: Higher total sugar intake and moderate added sugar intake were associated with lower frailty risk in older Korean adults. These findings highlight the importance of considering both the amount and source of dietary sugars when developing nutritional guidelines for healthy aging. Future policies should focus on nuanced dietary recommendations rather than universal restriction for the elderly population.

Protein misfolding and aggregation are cardinal features of neurodegenerative disease (NDD) and they contribute to pathophysiology by both loss-of-function (LOF) and gain-of-function (GOF) mechanisms. This is well exemplified by TDP-43 which aggregates and mislocalizes in several NDDs. The depletion of nuclear TDP-43 leads to reduction in its normal function in RNA metabolism and the cytoplasmic accumulation of TDP-43 leads to aberrant protein homeostasis. A modifier screen found that loss of...

Evidence suggests that cancer-related accelerated aging contributes to an earlier onset of chronic diseases; persistent symptoms; and decrements in patients' quality of life. This review presents the Multifactorial Model of Cancer-related Accelerated Aging (MMCRAA), a conceptual framework that is grounded in Life Course Theory and supported by empiric evidence. The model includes six inter-related concepts: person, behavioral, biological, treatment, symptom, and life course factors. The MMCRAA...

Chronic inflammation promotes aging and age-associated diseases. While metabolic interventions can modulate inflammation, how metabolism and inflammation are connected remains unclear. Cytoplasmic chromatin fragments (CCFs) drive chronic inflammation through the cGAS-STING pathway in senescence and aging. However, CCFs are larger than nuclear pores, and how they translocate from the nucleus to the cytoplasm remains uncharacterized. Here we report that chromatin fragments exit the nucleus via...

CONCLUSIONS: A sense of physical and mental health has a key impact on SA. Important moderators of SA include individual agency, sociodemographic factors, and, in particular, education level and household type. Due to the difficulties in defining unambiguous quality criteria, SA should be treated as a linear variable.

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Aging of the blood system impacts systemic health and can be traced to hematopoietic stem cells (HSCs). Despite multiple reports on human HSC aging, a unified map detailing their molecular age-related changes is lacking. We developed a consensus map of gene expression in HSCs by integrating seven single-cell datasets. This map reveals previously unappreciated heterogeneity within the HSC population. It also links inflammatory pathway activation (TNF/NFκB, AP-1) and quiescence within a single...

Infection triggers one of the most dramatic systemic responses in the body, and the coordinated activation and function of immune cells requires a dynamic regulation of transcriptomes and proteomes. This is achieved by RNA-binding proteins, which, together with RNA, form ribonucleoproteins. These proteins expand the information content of the genome and determine the lifespan, localization and function of RNA. Moreover, they control when, where and how much protein is produced. They can also...

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Aging and DNA damage increase the risk of chronic inflammation and autoimmunity, yet the molecular underpinnings remain unclear. In this study, we uncover a DNA damage-driven mechanism in macrophages that triggers immune autoreactivity. Here, using Er1^(Lyz2/)^(-) mice with a macrophage-specific DNA repair defect in ERCC1-XPF, we demonstrate that monocyte-derived macrophages accumulate DNA damage, activate the immune system, drive polyclonal T cell responses and generate antinuclear...

CONCLUSION: Community activation is a complex, multidisciplinary process that requires inclusive collaboration and local ownership. The Community Activation Compass offers a promising framework to guide such efforts, but further implementation and evaluation are needed to assess its impact on ageing in place.

The aging of the hematopoietic system is central to physiological aging, with profound consequences for immune competence, tissue regeneration, and systemic health. Age-related changes manifest as altered blood cell composition, functional decline in hematopoietic stem cells (HSCs), and deterioration of the bone marrow niche. Beyond hematologic dysfunction, hematopoietic aging acts as a systemic amplifier of age-related diseases through clonal hematopoiesis and inflammatory remodeling. This...

Aging populations require scalable strategies to delay or prevent dementia. Beyond the prevention of neurological injury associated with seasonal influenza, vaccination may help mitigate vascular and neuroinflammatory injury underlying cognitive impairment. Influenza infection can cause a marked short‑term increase in myocardial infarction risk, and acute infections have also been associated with transient increases in stroke risk. Experimental models show prolonged microglial activation and...

Replicative senescence frequently occurs in in vitro cell cultures and certain in vivo pathological conditions, characterized by multiple phenotypes, including cell cycle arrest. Previous studies suggested that the main mechanism underlying replicative senescence is that under continuous subculture, cells sense DNA damage during G1, which triggers G1/S arrest and the subsequent geroconversion. However, this explanation does not account for phenomena such as how DNA damage caused by replication...