Aging, Lifespan & Longevity

Rac1 promotes kidney collecting duct integrity by limiting actomyosin activity

1 month 2 weeks ago
A polarized collecting duct (CD), formed from the branching ureteric bud (UB), is a prerequisite for an intact kidney. The small Rho GTPase Rac1 is critical for actin cytoskeletal regulation. We investigated the role of Rac1 in the kidney collecting system by selectively deleting it in mice at the initiation of UB development. The mice exhibited only a mild developmental phenotype; however, with aging, the CD developed a disruption of epithelial integrity and function. Despite intact integrin...
Fabian Bock

p107 mediated mitochondrial function controls muscle stem cell proliferative fates

1 month 2 weeks ago
Muscle diseases and aging are associated with impaired myogenic stem cell self-renewal and fewer proliferating progenitors (MPs). Importantly, distinct metabolic states induced by glycolysis or oxidative phosphorylation have been connected to MP proliferation and differentiation. However, how these energy-provisioning mechanisms cooperate remain obscure. Herein, we describe a mechanism by which mitochondrial-localized transcriptional co-repressor p107 regulates MP proliferation. We show p107...
Debasmita Bhattacharya

Shear relaxation governs fusion dynamics of biomolecular condensates

1 month 2 weeks ago
Phase-separated biomolecular condensates must respond agilely to biochemical and environmental cues in performing their wide-ranging cellular functions, but our understanding of condensate dynamics is lagging. Ample evidence now indicates biomolecular condensates as viscoelastic fluids, where shear stress relaxes at a finite rate, not instantaneously as in viscous liquids. Yet the fusion dynamics of condensate droplets has only been modeled based on viscous liquids, with fusion time given by the...
Archishman Ghosh

dNTPpoolDB: a manually curated database of experimentally determined dNTP pools and pool changes in biological samples

1 month 2 weeks ago
Stimulated by the growing interest in the role of dNTP pools in physiological and malignant processes, we established dNTPpoolDB, the database that offers access to quantitative data on dNTP pools from a wide range of species, experimental and developmental conditions (https://dntppool.org/). The database includes measured absolute or relative cellular levels of the four canonical building blocks of DNA and of exotic dNTPs, as well. In addition to the measured quantity, dNTPpoolDB contains ample...
Rita Pancsa

mRNA vaccine-induced T cells respond identically to SARS-CoV-2 variants of concern but differ in longevity and homing properties depending on prior infection status

1 month 2 weeks ago
While mRNA vaccines are proving highly efficacious against SARS-CoV-2, it is important to determine how booster doses and prior infection influence the immune defense they elicit, and whether they protect against variants. Focusing on the T cell response, we conducted a longitudinal study of infection-naïve and COVID-19 convalescent donors before vaccination and after their first and second vaccine doses, using a high-parameter CyTOF analysis to phenotype their SARS-CoV-2-specific T cells....
Jason Neidleman

A leucine-derived fatty acid unlocks the mTOR to development

1 month 2 weeks ago
Understanding how nutrient-sensitive signaling pathways regulate development and aging is an active area of research. In this issue of Developmental Cell,Zhu and colleagues (2021) identify a specific monomethylated branched-chain fatty acid that overrides nutrient deprivation signaling and activates mTORC1 in C. elegans and mammalian cells.
Chung-Yang Yeh

From corpora amylacea to wasteosomes: History and perspectives

1 month 2 weeks ago
Corpora amylacea (CA) have been described in several human organs and have been associated with ageing and several pathological conditions. Although they were first discovered two centuries ago, their function and significance have not yet been identified. Here, we provide a chronological summary of the findings on CA in various organs and identify their similarities. After collecting and integrating these findings, we propose to consider CA as waste containers created by specific cells, which...
Marta Riba

Matters of size: Roles of hyaluronan in CNS aging and disease

1 month 2 weeks ago
Involvement of extracellular matrix (ECM) components in aging and age-related neurodegeneration is not well understood. The role of hyaluronan (HA), a major extracellular matrix glycosaminoglycan, in malignancy and inflammation is gaining new understanding. In particular, the differential biological effects of high molecular weight (HMW-HA) and low molecular weight hyaluronan (LMW-HA), and the mechanism behind such differences are being uncovered. Tightly regulated in the brain, HA can have...
Frances Tolibzoda Zakusilo

Coupling high-throughput mapping with proteomics analysis delineates cis-regulatory elements at high resolution

1 month 2 weeks ago
Growing evidence suggests that functional cis-regulatory elements (cis-REs) not only exist in epigenetically marked but also in unmarked sites of the human genome. While it is already difficult to identify cis-REs in the epigenetically marked sites, interrogating cis-REs residing within the unmarked sites is even more challenging. Here, we report adapting Reel-seq, an in vitro high-throughput (HTP) technique, to fine-map cis-REs at high resolution over a large region of the human genome in a...
Ting Wu

SomaMutDB: a database of somatic mutations in normal human tissues

1 month 2 weeks ago
De novo mutations, a consequence of errors in DNA repair or replication, have been reported to accumulate with age in normal tissues of humans and model organisms. This accumulation during development and aging has been implicated as a causal factor in aging and age-related pathology, including but not limited to cancer. Due to their generally very low abundance mutations have been difficult to detect in normal tissues. Only with recent advances in DNA sequencing of single-cells, clonal lineages...
Shixiang Sun

Enhancing mask activity in dopaminergic neurons extends lifespan in flies

1 month 2 weeks ago
Dopaminergic neurons (DANs) are essential modulators for brain functions involving memory formation, reward processing, and decision-making. Here I demonstrate a novel and important function of the DANs in regulating aging and longevity. Overexpressing the putative scaffolding protein Mask in two small groups of DANs in flies can significantly extend the lifespan in flies and sustain adult locomotor and fecundity at old ages. This Mask-induced beneficial effect requires dopaminergic transmission...
Xiaolin Tian

High-spatial and colourimetric imaging of histone modifications in single senescent cells using plasmonic nanoprobes

1 month 2 weeks ago
Histones are closely related to the state of chromatin, and epigenetic modification of their tail results in regulation in cells. Therefore, developing various analytical tools to map the changes in position and distribution of histone modifications is helpful in studying underlying mechanisms. Herein, we propose a high-spatial and colourimetric imaging method using plasmonic nanoparticles as probes to visualize heterochromatin histone markers in a single nucleus. We visualized the...
Hyun Ji An

Hair shaft miniaturization causes stem cell depletion through mechanosensory signals mediated by a Piezo1-calcium-TNF-α axis

1 month 2 weeks ago
In aging, androgenic alopecia, and genetic hypotrichosis disorders, hair shaft miniaturization is often associated with hair follicle stem cell (HFSC) loss. However, the mechanism causing this stem cell depletion in vivo remains elusive. Here we show that hair shaft loss or a reduction in diameter shrinks the physical niche size, which results in mechanical compression of HFSCs and their apoptotic loss. Mechanistically, cell compression activates the mechanosensitive channel Piezo1, which...
Yuhua Xie

Hinfp is a guardian of the somatic genome by repressing transposable elements

1 month 2 weeks ago
Germ cells possess the Piwi-interacting RNA pathway to repress transposable elements and maintain genome stability across generations. Transposable element mobilization in somatic cells does not affect future generations, but nonetheless can lead to pathological outcomes in host tissues. We show here that loss of function of the conserved zinc-finger transcription factor Hinfp causes dysregulation of many host genes and derepression of most transposable elements. There is also substantial DNA...
Niraj K Nirala

Temporal evolution of master regulator Crp identifies pyrimidines as catabolite modulator factors

1 month 2 weeks ago
The evolution of microorganisms often involves changes of unclear relevance, such as transient phenotypes and sequential development of multiple adaptive mutations in hotspot genes. Previously, we showed that ageing colonies of an E. coli mutant unable to produce cAMP when grown on maltose, accumulated mutations in the crp gene (encoding a global transcription factor) and in genes involved in pyrimidine metabolism such as cmk; combined mutations in both crp and cmk enabled fermentation of...
Ida Lauritsen

Commensal microbiota divergently affect myeloid subsets in the mammalian central nervous system during homeostasis and disease

1 month 2 weeks ago
The immune cells of the central nervous system (CNS) comprise parenchymal microglia and at the CNS border regions meningeal, perivascular, and choroid plexus macrophages (collectively called CNS-associated macrophages, CAMs). While previous work has shown that microglial properties depend on environmental signals from the commensal microbiota, the effects of microbiota on CAMs are unknown. By combining several microbiota manipulation approaches, genetic mouse models, and single-cell...
Roman Sankowski

A glimpse at the metabolic research in China

1 month 3 weeks ago
Over the last few decades, China has witnessed a great leap in economic growth and social welfare. Unfortunately, Chinese people have also been affected by a pandemic of over-nutrition, lack of physical activity, and increasing prevalence of metabolic disorders including obesity, diabetes, non-alcohol fatty liver disease, and cardiovascular disease. For instance, China currently has the largest number of diabetic patients (∼116 million) in the world. The fire of metabolic disorders is further...
Xiao-Wei Chen

NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load

1 month 3 weeks ago
Apolipoprotein E4 (ApoE4) is the most important and prevalent risk factor for late-onset Alzheimer's disease (AD). The isoelectric point of ApoE4 matches the pH of the early endosome (EE), causing its delayed dissociation from ApoE receptors and hence impaired endolysosomal trafficking, disruption of synaptic homeostasis, and reduced amyloid clearance. We have shown that enhancing endosomal acidification by inhibiting the EE-specific sodium-hydrogen exchanger 6 (NHE6) restores vesicular...
Theresa Pohlkamp
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