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CONCLUSIONS AND IMPLICATIONS: The risk of all-cause mortality declined among older adults with a reversal of frailty. Hemoglobin concentration and exercise contributed to the reversal of frailty among older adults. In contrast, aging, long daily sedentary time, cigarette smoking, and illiteracy were risk factors for the reversal of frailty. These findings may provide better strategies for frailty intervention.

Haemophilia A and B are congenital X-linked bleeding disorders resulting from deficiencies in clotting factors VIII (haemophilia A) and IX (haemophilia B). Patients with severe deficiency, defined as having less than 1% of normal plasma factor activivity, often have spontaneous bleeding within the first few years of life. Those with moderate and mild deficiencies typically present with post-traumatic or post-surgical bleeding later in life. A high index of suspicion and measurement of factor...

Recent studies have reported that the spaceflight environment lengthens leukocyte telomeres. We propose that this baffling finding reflects changes in the composition of leukocyte subsets rather than an actual increase in telomere length within individual leukocytes. Since leukocyte telomere length is associated with aging-related diseases and longevity in humans, it is crucial to understand the underlying factors driving telomere length changes in space.

Oxidative stress is widely recognized as a key contributor to the pathogenesis of Alzheimer's disease (AD). While not the sole factor, it is closely linked to critical pathological features, such as the formation of senile plaques and neurofibrillary tangles. The development of agents with antioxidant properties has become an area of growing interest in AD research. Between 2015 and 2024, several antioxidant-targeted drugs for AD progressed to clinical trials, with increasing attention to the...

Alzheimer's disease (AD) is a globally recognized neurodegenerative disorder that severely impairs cognitive function and imposes substantial psychological and financial burdens on patients and their families. The hallmark pathological features of AD include progressive neurodegeneration, extracellular beta-amyloid (Aβ) plaque accumulation, and intracellular hyperphosphorylated tau protein tangles. However, recent studies have identified a subset of patients exhibiting cognitive resilience,...

CONCLUSIONS: Neuropsychiatric symptoms occur commonly in MCI participants, and are mainly related to defect of language and memory function. A better understanding of the relationship between specific cognition and NPS may alert clinicians to pay close attention to the NPS in MCI patient, which may need early intervention.

CONCLUSION: Elevated late-life cholesterol may protect cognitive function in healthy individuals and those with mild impairment, with a sex-specific impact in dementia, beneficial for women but detrimental for men.

CONCLUSIONS: We developed an explainable machine learning model to predict SO in aging community and nursing populations. This model offers a novel, accessible, and interpretable approach to SO prediction with potential to enhance early detection and intervention strategies. Further studies are warranted to validate our model in diverse populations and evaluate its impact on patient outcomes when integrated into comprehensive geriatric assessments.

Retinoic acid (RA) is a standard-of-care neuroblastoma drug thought to be effective by inducing differentiation. Curiously, RA has little effect on primary human tumors during upfront treatment but can eliminate neuroblastoma cells from the bone marrow during post-chemo maintenance therapy-a discrepancy that has never been explained. To investigate this, we treat a large cohort of neuroblastoma cell lines with RA and observe that the most RA-sensitive cells predominantly undergo apoptosis or...

Senescence-associated secretory phenotype (SASP) mediates the biological effects of senescent cells on the tissue microenvironment and contributes to ageing-associated disease progression. ACSS2 produces acetyl-CoA from acetate and epigenetically controls gene expression through histone acetylation under various circumstances. However, whether and how ACSS2 regulates cellular senescence remains unclear. Here, we show that pharmacological inhibition and deletion of Acss2 in mice blunts SASP and...

The brain is a high-energy tissue, and although aging is associated with dysfunctional inflammatory and neuron-specific functional pathways, a direct connection to metabolism is not established. Here, we show that isoforms of mitochondrial regulator PGC-1α are driven from distinct brain cell-type specific promotors, repressed with aging, and integral in coordinating metabolism and growth signaling. Transcriptional and proteomic profiles of cortex from male adult, middle age, and advanced age...

The accuracy of protein synthesis and its relation to ageing has been of long-standing interest. To study whether spontaneous changes in the rate of ribosomal error occur as a function of age, we first determined that stop-codon readthrough is a more sensitive read-out of mistranslation due to codon-anticodon mispairing than missense amino acid incorporation. Subsequently, we developed knock-in mice for in-vivo detection of stop-codon readthrough using a gain-of-function Kat2-TGA-Fluc...

Human lifespan is shaped by genetic and environmental factors. To enable precision health, understanding how genetic variants influence mortality is essential. We conducted a survival analysis in European ancestry participants of the UK Biobank, using age-at-death (N=35,551) and last-known-age (N=358,282). The associations identified were predominantly driven by cancer. We found lifespan-associated loci (APOE, ZSCAN23) for common variants and six genes where burden of loss-of-function variants...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting millions worldwide. There is no known cure for AD, highlighting an urgent need for new, innovative treatments. Recent studies have shed light on a promising, noninvasive approach using sensory stimulation as a potential therapy for AD. Exposing patients to light and sound pulses at a frequency of 40 hertz induces brain rhythms in the gamma frequency range that are important for healthy brain activity. Using this...

Fraud undermines Alzheimer's disease research.

The Parkinson's disease-linked kinase, PINK1, is a short-lived protein that undergoes cleavage upon mitochondrial import leading to its proteasomal degradation. Under depolarizing conditions, it accumulates on mitochondria where it becomes activated, phosphorylating both ubiquitin and the ubiquitin E3 ligase Parkin, at Ser^(65). Our experiments reveal that in retinal pigment epithelial cells, only a fraction of PINK1 becomes stabilized after depolarization by electron transport chain inhibitors....

Neurogenesis and gliogenesis continue in the ventricular-subventricular zone (V-SVZ) of the adult rodent brain. V-SVZ astroglial cells with apical contact with the ventricle (B1 cells) function as neural stem cells (NSCs). B1 cells sharply decline during early postnatal life; in contrast, neurogenesis decreases at a slower rate. Here, we show that a second population of astroglia (B2 cells) that do not contact the ventricle also function as NSCs in the adult mouse brain. B2 cell numbers increase...

How and why is working memory (WM) capacity limited? Traditional cognitive accounts focus either on limitations on the number or items that can be stored (slots models), or loss of precision with increasing load (resource models). Here, we show that a neural network model of prefrontal cortex and basal ganglia can learn to reuse the same prefrontal populations to store multiple items, leading to resource-like constraints within a slot-like system, and inducing a trade-off between quantity and...

The buildup of knot-like RNA structures in brain cells may be the key to understanding how uncontrolled protein aggregation drives Alzheimer's disease.

The buildup of knot-like RNA structures in brain cells may be the key to understanding how uncontrolled protein aggregation drives Alzheimer's disease.