Aging & Longevity

Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage

1 month 2 weeks ago
Cerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes^(1-17), but the connections and regulation have been challenging to identify. Here, using fluorescent CSF tracers in Prox1-GFP lymphatic reporter mice^(18), we found that the nasopharyngeal lymphatic plexus is a major hub for CSF outflow to deep cervical lymph nodes. This plexus had unusual valves and short lymphangions but no smooth-muscle coverage,...
Jin-Hui Yoon

TIMely connections: APOE4, aging, and Alzheimer's

1 month 2 weeks ago
How do APOE4 and aging, two of the strongest risk factors for late-onset Alzheimer's disease (AD), promote disease progression? In this issue of Immunity, Millet et al. examine microglia in AD mice bearing different APOE alleles at distinct ages and identify a conserved exhausted-like microglial state enriched in very elderly and APOE4 AD brains.
Qingyun Li

Emerging role of NEDD8-mediated neddylation in age-related metabolic diseases

1 month 2 weeks ago
Aging in humans is associated with abdominal distribution and remodeling of body fat and a parallel gradual increase in the prevalence of metabolic diseases such as obesity, type 2 diabetes mellitus and fatty liver disease, as well as the risk of developing metabolic complications. Current treatments might be improved by understanding the detailed mechanisms underlying the onset of age-related metabolic disorders. Neddylation, a post-translational modification that adds the ubiquitin-like...
Mei Yu

A single-cell atlas of the aging mouse ovary

1 month 2 weeks ago
Ovarian aging leads to diminished fertility, dysregulated endocrine signaling and increased chronic disease burden. These effects begin to emerge long before follicular exhaustion. Female humans experience a sharp decline in fertility around 35 years of age, which corresponds to declines in oocyte quality. Despite a growing body of work, the field lacks a comprehensive cellular map of the transcriptomic changes in the aging mouse ovary to identify early drivers of ovarian decline. To fill this...
José V V Isola

TIME-seq reduces time and cost of DNA methylation measurement for epigenetic clock construction

1 month 2 weeks ago
Epigenetic 'clocks' based on DNA methylation have emerged as the most robust and widely used aging biomarkers, but conventional methods for applying them are expensive and laborious. Here we develop tagmentation-based indexing for methylation sequencing (TIME-seq), a highly multiplexed and scalable method for low-cost epigenetic clocks. Using TIME-seq, we applied multi-tissue and tissue-specific epigenetic clocks in over 1,800 mouse DNA samples from eight tissue and cell types. We show that...
Patrick T Griffin

The structure of B-ARR reveals the molecular basis of transcriptional activation by cytokinin

1 month 2 weeks ago
The phytohormone cytokinin has various roles in plant development, including meristem maintenance, vascular differentiation, leaf senescence, and regeneration. Prior investigations have revealed that cytokinin acts via a phosphorelay similar to the two-component system by which bacteria sense and respond to external stimuli. The eventual targets of this phosphorelay are type-B ARABIDOPSIS RESPONSE REGULATORS (B-ARRs), containing the conserved N-terminal receiver domain (RD), middle DNA binding...
Chuan-Miao Zhou

Rapid and synchronous chemical induction of replicative-like senescence via a small molecule inhibitor

1 month 2 weeks ago
Cellular senescence is acknowledged as a key contributor to organismal ageing and late-life disease. Though popular, the study of senescence in vitro can be complicated by the prolonged and asynchronous timing of cells committing to it and by its paracrine effects. To address these issues, we repurposed a small molecule inhibitor, inflachromene (ICM), to induce senescence to human primary cells. Within 6 days of treatment with ICM, senescence hallmarks, including the nuclear eviction of HMGB1...
Spiros Palikyras

DMH<sup>Ppp1r17</sup> neurons regulate aging and lifespan in mice through hypothalamic-adipose inter-tissue communication

1 month 2 weeks ago
Recent studies have shown that the hypothalamus functions as a control center of aging in mammals that counteracts age-associated physiological decline through inter-tissue communications. We have identified a key neuronal subpopulation in the dorsomedial hypothalamus (DMH), marked by Ppp1r17 expression (DMH^(Ppp1r17) neurons), that regulates aging and longevity in mice. DMH^(Ppp1r17) neurons regulate physical activity and WAT function, including the secretion of extracellular nicotinamide...
Kyohei Tokizane

The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34

1 month 2 weeks ago
Microglia harness an unutilized health-promoting potential in age-related neurodegenerative and neuroinflammatory diseases, conditions like progressive multiple sclerosis (MS). Our research unveils an microglia population emerging in the cortical brain regions of aging mice, marked by ERK1/2, Akt, and AMPK phosphorylation patterns and a transcriptome indicative of activated autophagy - a process critical for cellular adaptability. By deleting the core autophagy gene Ulk1 in microglia, we reduce...
Rasmus Berglund

Drone-based displacement measurement of infrastructures utilizing phase information

1 month 2 weeks ago
Drone-based inspections provide an efficient and flexible approach to assessing aging infrastructures while prioritizing safety. Here, we present a pioneering framework that employs drone cameras for high-precision displacement measurement and achieves sub-millimeter accuracy, meeting the requirements for on-site inspections. Inspired by the principles of human auditory equilibrium, we have developed an effective scheme using a group of strategical reference markers on the bridge girders to...
Shien Ri

Scalable nano-architecture for stable near-blackbody solar absorption at high temperatures

1 month 2 weeks ago
Light trapping enhancement by nanostructures is ubiquitous in engineering applications, for example, in improving highly-efficient concentrating solar thermal (CST) technologies. However, most nano-engineered coatings and metasurfaces are not scalable to large surfaces ( > 100 m²) and are unstable at elevated temperatures ( > 850 ^(°)C), hindering their wide-spread adoption in CST. Here, we propose a scalable layer nano-architecture that can significantly enhance the solar absorption of an...
Yifan Guo

Gasdermin E dictates inflammatory responses by controlling the mode of neutrophil death

1 month 2 weeks ago
Both lytic and apoptotic cell death remove senescent and damaged cells in living organisms. However, they elicit contrasting pro- and anti-inflammatory responses, respectively. The precise cellular mechanism that governs the choice between these two modes of death remains incompletely understood. Here we identify Gasdermin E (GSDME) as a master switch for neutrophil lytic pyroptotic death. The tightly regulated GSDME cleavage and activation in aging neutrophils are mediated by proteinase-3 and...
Fengxia Ma

Spartin-mediated lipid transfer facilitates lipid droplet turnover

1 month 2 weeks ago
Lipid droplets (LDs) are organelles critical for energy storage and membrane lipid homeostasis, whose number and size are carefully regulated in response to cellular conditions. The molecular mechanisms underlying lipid droplet biogenesis and degradation, however, are not well understood. The Troyer syndrome protein spartin (SPG20) supports LD delivery to autophagosomes for turnover via lipophagy. Here, we characterize spartin as a lipid transfer protein whose transfer ability is required for LD...
Neng Wan

Climate migration amplifies demographic change and population aging

1 month 2 weeks ago
The warnings of potential climate migration first appeared in the scientific literature in the late 1970s when increased recognition that disintegrating ice sheets could drive people to migrate from coastal cities. Since that time, scientists have modeled potential climate migration without integrating other population processes, potentially obscuring the demographic amplification of this migration. Climate migration could amplify demographic change-enhancing migration to destinations and...
Mathew E Hauer

Accurate estimation of biological age and its application in disease prediction using a multimodal image Transformer system

1 month 2 weeks ago
Aging in an individual refers to the temporal change, mostly decline, in the body's ability to meet physiological demands. Biological age (BA) is a biomarker of chronological aging and can be used to stratify populations to predict certain age-related chronic diseases. BA can be predicted from biomedical features such as brain MRI, retinal, or facial images, but the inherent heterogeneity in the aging process limits the usefulness of BA predicted from individual body systems. In this paper, we...
Jinzhuo Wang

An acyl-CoA thioesterase is essential for the biosynthesis of a key dauer pheromone in C. elegans

1 month 3 weeks ago
Methyl ketone (MK)-ascarosides represent essential components of several pheromones in Caenorhabditis elegans, including the dauer pheromone, which triggers the stress-resistant dauer larval stage, and the male-attracting sex pheromone. Here, we identify an acyl-CoA thioesterase, ACOT-15, that is required for the biosynthesis of MK-ascarosides. We propose a model in which ACOT-15 hydrolyzes the β-keto acyl-CoA side chain of an ascaroside intermediate during β-oxidation, leading to...
Subhradeep Bhar

Hallmarks of stemness in mammalian tissues

1 month 3 weeks ago
All adult tissues experience wear and tear. Most tissues can compensate for cell loss through the activity of resident stem cells. Although the cellular maintenance strategies vary greatly between different adult (read: postnatal) tissues, the function of stem cells is best defined by their capacity to replace lost tissue through division. We discuss a set of six complementary hallmarks that are key enabling features of this basic function. These include longevity and self-renewal, multipotency,...
Joep Beumer
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