Aging & Longevity
Modified lentiviral globin gene therapy for pediatric β<sup>0</sup>/β<sup>0</sup> transfusion-dependent β-thalassemia: A single-center, single-arm pilot trial
β⁰/β⁰ thalassemia is the most severe type of transfusion-dependent β-thalassemia (TDT) and is still a challenge facing lentiviral gene therapy. Here, we report the interim analysis of a single-center, single-arm pilot trial (NCT05015920) evaluating the safety and efficacy of a β-globin expression-optimized and insulator-engineered lentivirus-modified cell product (BD211) in β⁰/β⁰ TDT. Two female children were enrolled, infused with BD211, and followed up for an average of 25.5 months....
Understanding Role of Pesticides in Development of Parkinson's Disease: Insights from Drosophila and Rodent Models
Parkinson's disease is a neurodegenerative illness linked to ageing, marked by the gradual decline of dopaminergic neurons in the midbrain. The exact aetiology of Parkinson's disease (PD) remains uncertain, with genetic predisposition and environmental variables playing significant roles in the disease's frequency. Epidemiological data indicates a possible connection between pesticide exposure and brain degeneration. Specific pesticides have been associated with important characteristics of...
Monosymmetric Fe-N<sub>4</sub> sites enabling durable proton exchange membrane fuel cell cathode by chemical vapor modification
The limited durability of metal-nitrogen-carbon electrocatalysts severely restricts their applicability for the oxygen reduction reaction in proton exchange membrane fuel cells. In this study, we employ the chemical vapor modification method to alter the configuration of active sites from FeN(4) to the stable monosymmetric FeN(2)+N'(2), along with enhancing the degree of graphitization in the carbon substrate. This improvement effectively addresses the challenges associated with Fe active center...
High-throughput mechanical phenotyping and transcriptomics of single cells
The molecular system regulating cellular mechanical properties remains unexplored at single-cell resolution mainly due to a limited ability to combine mechanophenotyping with unbiased transcriptional screening. Here, we describe an electroporation-based lipid-bilayer assay for cell surface tension and transcriptomics (ELASTomics), a method in which oligonucleotide-labelled macromolecules are imported into cells via nanopore electroporation to assess the mechanical state of the cell surface and...
Breaking down causes, consequences, and mediating effects of telomere length variation on human health
CONCLUSIONS: Our study sheds light on the modulators, consequences, and the mediatory role of telomeres, portraying an intricate relationship between LTL, diseases, lifestyle, and socio-economic factors.
Remembering Judy Campisi: Fearless scientist and pioneer in cellular senescence
No abstract
Mitochondrial ACSS1-K635 acetylation knock-in mice exhibit altered metabolism, cell senescence, and nonalcoholic fatty liver disease
Acetyl-CoA synthetase short-chain family member 1 (ACSS1) uses acetate to generate mitochondrial acetyl-CoA and is regulated by deacetylation by sirtuin 3. We generated an ACSS1-acetylation (Ac) mimic mouse, where lysine-635 was mutated to glutamine (K635Q). Male Acss1^(K635Q/K635Q) mice were smaller with higher metabolic rate and blood acetate and decreased liver/serum ATP and lactate levels. After a 48-hour fast, Acss1^(K635Q/K635Q) mice presented hypothermia and liver aberrations, including...
Ketogenic diet induces p53-dependent cellular senescence in multiple organs
A ketogenic diet (KD) is a high-fat, low-carbohydrate diet that leads to the generation of ketones. While KDs improve certain health conditions and are popular for weight loss, detrimental effects have also been reported. Here, we show mice on two different KDs and, at different ages, induce cellular senescence in multiple organs, including the heart and kidney. This effect is mediated through adenosine monophosphate-activated protein kinase (AMPK) and inactivation of mouse double minute 2...
Identification of Prominin-2 as a new player of cardiomyocyte senescence in the aging heart
The aging heart is characterized by a number of structural changes leading to ventricular stiffness, impaired resistance to stress and increased risk of developing heart failure (HF). Genetic or pharmacological removal of senescent cells has recently demonstrated the possibility to relieve some cardiac aging features such as hypertrophy and fibrosis. However, the contribution of the different cell types in cardiac aging remains fragmentary due to a lack of cell-specific markers. Cardiomyocytes...
Humanin P3S, haplogroup N1b and the risk of Alzheimer's disease
A commentary of the paper 'Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4-induced brain pathology' that appeared recently in Aging Cell. The possible association of a mitochondrial haplogroup with a disease is frequently discussed. The Humanin peptide encoded by the mtDNA has been shown to play an important regulatory role in cell metabolism. There are variants of Humanin caused by different mutations and it is known that the potent form of Humanin, termed...
Age-related and species-specific methylation changes in the protein-coding marmoset sperm epigenome
The sperm epigenome is thought to affect the developmental programming of the resulting embryo, influencing health and disease in later life. Age-related methylation changes in the sperm of old fathers may mediate the increased risks for reproductive and offspring medical problems. The impact of paternal age on sperm methylation has been extensively studied in humans and, to a lesser extent, in rodents and cattle. Here, we performed a comparative analysis of paternal age effects on...
The integrated stress response promotes neural stem cell survival under conditions of mitochondrial dysfunction in neurodegeneration
Impaired mitochondrial function is a hallmark of aging and a major contributor to neurodegenerative diseases. We have shown that disrupted mitochondrial dynamics typically found in aging alters the fate of neural stem cells (NSCs) leading to impairments in learning and memory. At present, little is known regarding the mechanisms by which neural stem and progenitor cells survive and adapt to mitochondrial dysfunction. Using Opa1-inducible knockout as a model of aging and neurodegeneration, we...
Severe drought exposure in utero associates to children's epigenetic age acceleration in a global climate change hot spot
The goal of this study is to examine the association between in utero drought exposure and epigenetic age acceleration (EAA) in a global climate change hot spot. Calculations of EAA in adults using DNA methylation have been found to accurately predict chronic disease and longevity. However, fewer studies have examined EAA in children, and drought exposure in utero has not been investigated. Additionally, studies of EAA in low-income countries with diverse populations are rare. We assess EAA...
Sustainable thermal regulation improves stability and efficiency in all-perovskite tandem solar cells
Mixed Sn-Pb perovskites have emerged as promising photovoltaic materials for both single- and multi-junction solar cells. However, achieving their scale-up and practical application requires further enhancement in stability. We identify that their poor thermal conductivity results in insufficient thermal transfer, leading to heat accumulation within the absorber layer that accelerates thermal degradation. A thermal regulation strategy by incorporating carboranes into perovskites is developed;...
Magnetic voluntary head-fixation in transgenic rats enables lifespan imaging of hippocampal neurons
The precise neural mechanisms within the brain that contribute to the remarkable lifetime persistence of memory are not fully understood. Two-photon calcium imaging allows the activity of individual cells to be followed across long periods, but conventional approaches require head-fixation, which limits the type of behavior that can be studied. We present a magnetic voluntary head-fixation system that provides stable optical access to the brain during complex behavior. Compared to previous...
Quantifying stochasticity in the aging DNA methylome
No abstract
Autophagy counters inflammation-driven glycolytic impairment in aging hematopoietic stem cells
Autophagy is central to the benefits of longevity signaling programs and to hematopoietic stem cell (HSC) response to nutrient stress. With age, a subset of HSCs increases autophagy flux and preserves regenerative capacity, but the signals triggering autophagy and maintaining the functionality of autophagy-activated old HSCs (oHSCs) remain unknown. Here, we demonstrate that autophagy is an adaptive cytoprotective response to chronic inflammation in the aging murine bone marrow (BM) niche. We...
Bandgap-universal passivation enables stable perovskite solar cells with low photovoltage loss
The efficiency and longevity of metal-halide perovskite solar cells are typically dictated by nonradiative defect-mediated charge recombination. In this work, we demonstrate a vapor-based amino-silane passivation that reduces photovoltage deficits to around 100 millivolts (>90% of the thermodynamic limit) in perovskite solar cells of bandgaps between 1.6 and 1.8 electron volts, which is crucial for tandem applications. A primary-, secondary-, or tertiary-amino-silane alone negatively or barely...
NSF halts South Pole probe of cosmic inflation
Aging infrastructure there cannot support suite of new telescopes, agency says.
Long-term hematopoietic transfer of the anti-cancer and lifespan-extending capabilities of a genetically engineered blood system by transplantation of bone marrow mononuclear cells
A causal relationship exists among the aging process, organ decay and disfunction, and the occurrence of various diseases including cancer. A genetically engineered mouse model, termed Klf1^(K74R/K74R) or Klf1(K74R), carrying mutation on the well-conserved sumoylation site of the hematopoietic transcription factor KLF1/EKLF has been generated that possesses extended lifespan and healthy characteristics, including cancer resistance. We show that the healthy longevity characteristics of the...
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