Aging & Longevity

Active growth signaling promotes senescence and cancer cell sensitivity to CDK7 inhibition

2 weeks 1 day ago
Tumor growth is driven by continued cellular growth and proliferation. Cyclin-dependent kinase 7's (CDK7) role in activating mitotic CDKs and global gene expression makes it therefore an attractive target for cancer therapies. However, what makes cancer cells particularly sensitive to CDK7 inhibition (CDK7i) remains unclear. Here, we address this question. We show that CDK7i, by samuraciclib, induces a permanent cell-cycle exit, known as senescence, without promoting DNA damage signaling or cell...
Gemma A Wilson

Age-associated H3K9me2 loss alters the regenerative equilibrium between murine lung alveolar and bronchiolar progenitors

2 weeks 1 day ago
The lung contains multiple progenitor cell types, but how their responses are choreographed during injury repair and whether this changes with age is poorly understood. We report that histone H3 lysine 9 di-methylation (H3K9me2), mediated by the methyltransferase G9a, regulates the dynamics of distal lung epithelial progenitor cells and that this regulation deteriorates with age. In aged mouse lungs, H3K9me2 loss coincided with fewer alveolar type 2 (AT2) cell progenitors and reduced alveolar...
Samuel P Rowbotham

Vitamin B<sub>12</sub> is a limiting factor for induced cellular plasticity and tissue repair

2 weeks 1 day ago
Transient reprogramming by the expression of OCT4, SOX2, KLF4 and MYC (OSKM) is a therapeutic strategy for tissue regeneration and rejuvenation, but little is known about its metabolic requirements. Here we show that OSKM reprogramming in mice causes a global depletion of vitamin B(12) and molecular hallmarks of methionine starvation. Supplementation with vitamin B(12) increases the efficiency of reprogramming both in mice and in cultured cells, the latter indicating a cell-intrinsic effect. We...
Marta Kovatcheva

Leukotriene A4 hydrolase inhibition improves age-related cognitive decline via modulation of synaptic function

2 weeks 1 day ago
Leukotrienes, a class of inflammatory bioactive lipids, are well studied in the periphery, but less is known of their importance in the brain. We identified that the enzyme leukotriene A4 hydrolase (LTA4H) is expressed in healthy mouse neurons, and inhibition of LTA4H in aged mice improves hippocampal dependent memory. Single-cell nuclear RNA sequencing of hippocampal neurons after inhibition reveals major changes to genes important for synaptic organization, structure, and activity. We propose...
Julia M Adams

Global, regional, and national prevalence of hearing loss from 1990 to 2019: A trend and health inequality analyses based on the Global Burden of Disease Study 2019

2 weeks 2 days ago
As a severe public health issue, hearing loss has caused an increasingly disease burden, especially in the elderly population. Hearing loss may inevitably induce asymmetric hearing, which makes it difficult for elderly individuals to locate sound sources, therefore resulting in increased postural instability and falling risk. To emphasize the public health emergence of hearing loss, we investigated the temporal trend of prevalence of hearing loss over the last 30 years and further predicted its...
Chuan-Ya Jiang

Cellular age explains variation in age-related cell-to-cell transcriptome variability

2 weeks 2 days ago
Organs and tissues age at different rates within a single individual. Such asynchrony in aging has been widely observed at multiple levels, from functional hallmarks, such as anatomical structures and physiological processes, to molecular endophenotypes, such as the transcriptome and metabolome. However, we lack a conceptual framework to understand why some components age faster than others. Just as demographic models explain why aging evolves, here we test the hypothesis that demographic...
Ming Yang

Circadian disturbances and frailty risk in older adults

2 weeks 2 days ago
Frailty is characterized by diminished resilience to stressor events. It is associated with adverse future health outcomes and impedes healthy aging. The circadian system orchestrates ~24-h rhythms in bodily functions in synchrony with the day-night cycle, and disturbed circadian regulation plays an important role in many age-related health consequences. We investigated prospective associations of circadian disturbances with incident frailty in over 1000 older adults who had been followed...
Ruixue Cai

Circulating monocytes expressing senescence-associated features are enriched in COVID-19 patients with severe disease

2 weeks 2 days ago
Accurate biomarkers for predicting COVID-19 severity have remained an unmet need due to an incomplete understanding of virus pathogenesis and heterogeneity among patients. Cellular senescence and its pro-inflammatory phenotype are suggested to be a consequence of SARS-CoV-2 infection and potentially drive infection-dependent pathological sequelae. Senescence-associated markers in infected individuals have been identified primarily in the lower respiratory tract, while little is known about their...
Y Lin

Proteome-wide profiling reveals dysregulated molecular features and accelerated aging in osteoporosis: A 9.8-year prospective study

2 weeks 2 days ago
The role of circulatory proteomics in osteoporosis is unclear. Proteome-wide profiling holds the potential to offer mechanistic insights into osteoporosis. Serum proteome with 413 proteins was profiled by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline, and the 2nd, and 3rd follow-ups (7704 person-tests) in the prospective Chinese cohorts with 9.8 follow-up years: discovery cohort (n = 1785) and internal validation cohort (n = 1630). Bone mineral density (BMD) was measured...
Jinjian Xu

Sex hormone signaling and regulation of immune function

2 weeks 3 days ago
Immune responses to antigens, including innocuous, self, tumor, microbial, and vaccine antigens, differ between males and females. The quest to uncover the mechanisms for biological sex differences in the immune system has intensified, with considerable literature pointing toward sex hormonal influences on immune cell function. Sex steroids, including estrogens, androgens, and progestins, have profound effects on immune function. As such, drastic changes in sex steroid concentrations that occur...
Joseph P Hoffmann

Factors affecting the GABAergic synapse function in Alzheimer's disease: Focus on microRNAs

2 weeks 3 days ago
Alzheimer's disease (AD) is a progressive neurological disease characterized by the loss of cognitive function, confusion, and memory deficit. Accumulation of abnormal proteins, amyloid beta (Aß), and phosphorylated Tau (p-tau) forms plaques and tangles that deteriorate synapse function, resulting in neurodegeneration and cognitive decline in AD. The human brain is composed of different types of neurons and/or synapses that are functionally defective in AD. The GABAergic synapse, the most...
Jazmin Rivera

The extracellular matrix dictates regional competence for tumour initiation

2 weeks 3 days ago
The skin epidermis is constantly renewed throughout life^(1,2). Disruption of the balance between renewal and differentiation can lead to uncontrolled growth and tumour initiation³. However, the ways in which oncogenic mutations affect the balance between renewal and differentiation and lead to clonal expansion, cell competition, tissue colonization and tumour development are unknown. Here, through multidisciplinary approaches that combine in vivo clonal analysis using intravital microscopy,...
Nordin Bansaccal

Parathyroid hormone treatment partially reverses endplate remodeling and attenuates low back pain in animal models of spine degeneration

2 weeks 3 days ago
Low back pain (LBP) is one of the most prevalent diseases affecting quality of life, with no disease-modifying therapy. During aging and spinal degeneration, the balance between the normal endplate (EP) bilayers of cartilage and bone shifts to more bone. The aged/degenerated bony EP has increased porosity because of osteoclastic remodeling activity and may be a source of LBP due to aberrant sensory innervation within the pores. We used two mouse models of spinal degeneration to show that...
Zemin Ling

rDNA magnification is a unique feature of germline stem cells

2 weeks 3 days ago
Ribosomal DNA (rDNA) encodes ribosomal RNA and exists as tandem repeats of hundreds of copies in the eukaryotic genome to meet the high demand of ribosome biogenesis. Tandemly repeated DNA elements are inherently unstable; thus, mechanisms must exist to maintain rDNA copy number (CN), in particular in the germline that continues through generations. A phenomenon called rDNA magnification was discovered over 50 y ago in Drosophila as a process that recovers the rDNA CN on chromosomes that harbor...
Jonathan O Nelson

Impaired end joining induces cardiac atrophy in a Hutchinson-Gilford progeria mouse model

2 weeks 3 days ago
Patients with Hutchinson-Gilford progeria syndrome (HGPS) present with a number of premature aging phenotypes, including DNA damage accumulation, and many of them die of cardiovascular complications. Although vascular pathologies have been reported, whether HGPS patients exhibit cardiac dysfunction and its underlying mechanism is unclear, rendering limited options for treating HGPS-related cardiomyopathy. In this study, we reported a cardiac atrophy phenotype in the Lmna^(G609G/G609G) mice...
Yu Chen

Mechanical loading and hyperosmolarity as a daily resetting cue for skeletal circadian clocks

2 weeks 4 days ago
Daily rhythms in mammalian behaviour and physiology are generated by a multi-oscillator circadian system entrained through environmental cues (e.g. light and feeding). The presence of tissue niche-dependent physiological time cues has been proposed, allowing tissues the ability of circadian phase adjustment based on local signals. However, to date, such stimuli have remained elusive. Here we show that daily patterns of mechanical loading and associated osmotic challenge within physiological...
Michal Dudek

Single-cell atlas of healthy human blood unveils age-related loss of NKG2C<sup>+</sup>GZMB<sup>-</sup>CD8<sup>+</sup> memory T cells and accumulation of type 2 memory T cells

2 weeks 4 days ago
Extensive, large-scale single-cell profiling of healthy human blood at different ages is one of the critical pending tasks required to establish a framework for the systematic understanding of human aging. Here, using single-cell RNA/T cell receptor (TCR)/BCR-seq with protein feature barcoding, we profiled 317 samples from 166 healthy individuals aged 25-85 years old. From this, we generated a dataset from ∼2 million cells that described 55 subpopulations of blood immune cells. Twelve...
Marina Terekhova

Stress, epigenetics, and aging: Unraveling the intricate crosstalk

2 weeks 4 days ago
Aging, as a complex process involving multiple cellular and molecular pathways, is known to be exacerbated by various stresses. Because responses to these stresses, such as oxidative stress and genotoxic stress, are known to interplay with the epigenome and thereby contribute to the development of age-related diseases, investigations into how such epigenetic mechanisms alter gene expression and maintenance of cellular homeostasis is an active research area. In this review, we highlight recent...
Zeming Wu
4 hours 43 minutes ago
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