Aging, Lifespan & Longevity

Human neocortical expansion involves glutamatergic neuron diversification

1 month 3 weeks ago
The neocortex is disproportionately expanded in human compared with mouse^(1,2), both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers composed of neurons that selectively make connections within the neocortex and with other telencephalic structures. Single-cell transcriptomic analyses of human and mouse neocortex show an increased diversity of glutamatergic neuron types in supragranular layers in human neocortex and pronounced...
Jim Berg

The cellular modifier MOAG-4/SERF drives amyloid formation through charge complementation

1 month 3 weeks ago
While aggregation-prone proteins are known to accelerate aging and cause age-related diseases, the cellular mechanisms that drive their cytotoxicity remain unresolved. The orthologous proteins MOAG-4, SERF1A, and SERF2 have recently been identified as cellular modifiers of such proteotoxicity. Using a peptide array screening approach on human amyloidogenic proteins, we found that SERF2 interacted with protein segments enriched in negatively charged and hydrophobic, aromatic amino acids. The...
Anita Pras

Modulation of fracture healing by the transient accumulation of senescent cells

1 month 3 weeks ago
Senescent cells have detrimental effects across tissues with aging but may have beneficial effects on tissue repair, specifically on skin wound healing. However, the potential role of senescent cells in fracture healing has not been defined. Here, we performed an in silico analysis of public mRNAseq data and found that senescence and senescence-associated secretory phenotype (SASP) markers increased during fracture healing. We next directly established that the expression of senescence...
Dominik Saul

Continuous variable responses and signal gating form kinetic bases for pulsatile insulin signaling and emergence of resistance

1 month 3 weeks ago
Understanding kinetic control of biological processes is as important as identifying components that constitute pathways. Insulin signaling is central for almost all metazoans, and its perturbations are associated with various developmental disorders, metabolic diseases, and aging. While temporal phosphorylation changes and kinetic constants have provided some insights, constant or variable parameters that establish and maintain signal topology are poorly understood. Here, we report kinetic...
Namrata Shukla

Dopamine, sleep, and neuronal excitability modulate amyloid-β-mediated forgetting in Drosophila

1 month 3 weeks ago
Alzheimer disease (AD) is one of the main causes of age-related dementia and neurodegeneration. However, the onset of the disease and the mechanisms causing cognitive defects are not well understood. Aggregation of amyloidogenic peptides is a pathological hallmark of AD and is assumed to be a central component of the molecular disease pathways. Pan-neuronal expression of Aβ42Arctic peptides in Drosophila melanogaster results in learning and memory defects. Surprisingly, targeted expression to...
Jenifer C Kaldun

A replication-linked mutational gradient drives somatic mutation accumulation and influences germline polymorphisms and genome composition in mitochondrial DNA

1 month 3 weeks ago
Mutations in mitochondrial DNA (mtDNA) cause maternally inherited diseases, while somatic mutations are linked to common diseases of aging. Although mtDNA mutations impact health, the processes that give rise to them are under considerable debate. To investigate the mechanism by which de novo mutations arise, we analyzed the distribution of naturally occurring somatic mutations across the mouse and human mtDNA obtained by Duplex Sequencing. We observe distinct mutational gradients in G→A and T→C...
Monica Sanchez-Contreras

Targeting senescent immune cells to rejuvenate the aging skeleton

1 month 3 weeks ago
Accumulation of senescent cells in the bone marrow leads to age-related bone degeneration. Identifying the key senescent cell types and the factors they release that are responsible for skeletal aging is of keen interest. In a new study by Li et al. (2021), it is shown that immune cells, including neutrophils and macrophages, are critical cell types in this aging process, and that they secrete grancalcin to promote such aging.
Ge Zhang

Senescent immune cells release grancalcin to promote skeletal aging

1 month 3 weeks ago
Skeletal aging is characterized by low bone turnover and marrow fat accumulation. However, the underlying mechanism for this imbalance is unclear. Here, we show that during aging in rats and mice proinflammatory and senescent subtypes of immune cells, including macrophages and neutrophils, accumulate in the bone marrow and secrete abundant grancalcin. The injection of recombinant grancalcin into young mice was sufficient to induce premature skeletal aging. In contrast, genetic deletion of Gca in...
Chang-Jun Li

Aging impairs human bone marrow function and cardiac repair following myocardial infarction in a humanized chimeric mouse

1 month 3 weeks ago
Ventricular remodeling following myocardial infarction (MI) is a major cause of heart failure, a condition prevalent in older individuals. Following MI, immune cells are mobilized to the myocardium from peripheral lymphoid organs and play an active role in orchestrating repair. While the effect of aging on mouse bone marrow (BM) has been studied, less is known about how aging affects human BM cells and their ability to regulate repair processes. In this study, we investigate the effect aging has...
Tina B Marvasti

Mitochondrial DNA copy number and heteroplasmy load correlate with skeletal muscle oxidative capacity by P31 MR spectroscopy

1 month 3 weeks ago
The association between blood-based estimates of mitochondrial DNA parameters, mitochondrial DNA copy number (mtDNA-CN) and heteroplasmy load, with skeletal muscle bioenergetic capacity was evaluated in 230 participants of the Baltimore Longitudinal Study of Aging (mean age:74.7 years, 53% women). Participants in the study sample had concurrent data on muscle oxidative capacity (τ(PCr) ) assessed by ^(31) P magnetic resonance spectroscopy, and mitochondrial DNA parameters estimated from...
Qu Tian

CDK2 phosphorylation of Werner protein (WRN) contributes to WRN's DNA double-strand break repair pathway choice

1 month 3 weeks ago
Werner syndrome (WS) is an accelerated aging disorder characterized by genomic instability, which is caused by WRN protein deficiency. WRN participates in DNA metabolism including DNA repair. In a previous report, we showed that WRN protein is recruited to laser-induced DNA double-strand break (DSB) sites during various stages of the cell cycle with similar intensities, supporting that WRN participates in both non-homologous end joining (NHEJ) and homologous recombination (HR). Here, we...
Jong-Hyuk Lee

Cytokinin regulates vegetative phase change in Arabidopsis thaliana through the miR172/TOE1-TOE2 module

1 month 3 weeks ago
During vegetative growth plants pass from a juvenile to an adult phase causing changes in shoot morphology. This vegetative phase change is primarily regulated by the opposite actions of two microRNAs, the inhibitory miR156 and the promoting miR172 as well as their respective target genes, constituting the age pathway. Here we show that the phytohormone cytokinin promotes the juvenile-to-adult phase transition through regulating components of the age pathway. Reduction of cytokinin signalling...
Sören Werner

C. elegans feed yolk to their young in a form of primitive lactation

1 month 3 weeks ago
The nematode Caenorhabditis elegans exhibits rapid senescence that is promoted by the insulin/IGF-1 signalling (IIS) pathway via regulated processes that are poorly understood. IIS also promotes production of yolk for egg provisioning, which in post-reproductive animals continues in an apparently futile fashion, supported by destructive repurposing of intestinal biomass that contributes to senescence. Here we show that post-reproductive mothers vent yolk which can be consumed by larvae and...
Carina C Kern

Microglia and CD206(+) border-associated mouse macrophages maintain their embryonic origin during Alzheimer's disease

1 month 3 weeks ago
Brain microglia and border-associated macrophages (BAMs) display distinct spatial, developmental, and phenotypic features. Although at steady state, the origins of distinct brain macrophages are well-documented, the dynamics of their replenishment in neurodegenerative disorders remain elusive, particularly for activated CD11c^(+) microglia and BAMs. In this study, we conducted a comprehensive fate-mapping analysis of murine microglia and BAMs and their turnover kinetics during Alzheimer's...
Xiaoting Wu

Interactions between glial cells and the blood-brain barrier and their role in Alzheimer's disease

1 month 3 weeks ago
Alzheimer's disease (AD), which is an irreversible neurodegenerative disorder characterized by senile plaques and neurofibrillary tangles, is the most common form of dementia worldwide. However, currently, there are no satisfying curative therapies for AD. The blood-brain barrier (BBB) acts as a selective physical barrier and plays protective roles in maintaining brain homeostasis. BBB dysfunction as an upstream or downstream event promotes the onset and progression of AD. Moreover, the...
Ming Zhao

Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce

1 month 3 weeks ago
Obesity is considered an important factor for many chronic diseases, including diabetes, cardiovascular disease and cancer. The expansion of adipose tissue in obesity is due to an increase in both adipocyte progenitor differentiation and mature adipocyte cell size. Adipocytes, however, are thought to be unable to divide or enter the cell cycle. We demonstrate that mature human adipocytes unexpectedly display a gene and protein signature indicative of an active cell cycle program. Adipocyte cell...
Qian Li

Phospholipase Cγ2 regulates endocannabinoid and eicosanoid networks in innate immune cells

1 month 3 weeks ago
Human genetic studies have pointed to a prominent role for innate immunity and lipid pathways in immunological and neurodegenerative disorders. Our understanding of the composition and function of immunomodulatory lipid networks in innate immune cells, however, remains incomplete. Here, we show that phospholipase Cγ2 (PLCγ2 or PLCG2)-mutations in which are associated with autoinflammatory disorders and Alzheimer's disease-serves as a principal source of diacylglycerol (DAG) pools that are...
Hui Jing

Iron homeostasis in arthropathies: From pathogenesis to therapeutic potential

1 month 3 weeks ago
Iron is an essential element for proper functioning of cells within mammalian organ systems; in particular, iron homeostasis is critical for joint health. Excess iron can induce oxidative stress damage, associated with the pathogenesis of iron-storage and ageing-related diseases. Therefore, iron levels in body tissues and cells must be tightly regulated. In the past decades, excess iron content within joints has been found in some patients with joint diseases including hemophilic arthropathy,...
Kai Sun
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Aging, Lifespan & Longevity
Aging: Latest results from PubMed
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