Aging & Longevity

EPB41L4A-AS1 is required to maintain basal autophagy to modulates Aβ clearance

2 weeks 6 days ago
Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by the deposition of β-amyloid (Aβ) plaques. Aβ is generated from the cleavage of the amyloid precursor protein by β and γ-secretases and cleared by neuroglial cells mediated autophagy. The imbalance of the intracellular Aβ generation and clearance is the causative factor for AD pathogenesis. However, the exact underlying molecular mechanisms remain unclear. Our previous study reported that EPB41L4A-AS1 is an...
Ziqiang Wang

Effects of emissions caps on the costs and feasibility of low-carbon hydrogen in the European ammonia industry

2 weeks 6 days ago
The European ammonia industry emits 36 million tons of carbon dioxide annually, primarily from steam methane reforming (SMR) hydrogen production. These emissions can be mitigated by producing hydrogen via water electrolysis using dedicated renewables with grid backup. This study investigates the impact of decarbonization targets for hydrogen synthesis on the economic viability and technical feasibility of retrofitting existing European ammonia plants for on-site, semi-islanded electrolytic...
Stefano Mingolla

Small-molecule-induced epigenetic rejuvenation promotes SREBP condensation and overcomes barriers to CNS myelin regeneration

3 weeks ago
Remyelination failure in diseases like multiple sclerosis (MS) was thought to involve suppressed maturation of oligodendrocyte precursors; however, oligodendrocytes are present in MS lesions yet lack myelin production. We found that oligodendrocytes in the lesions are epigenetically silenced. Developing a transgenic reporter labeling differentiated oligodendrocytes for phenotypic screening, we identified a small-molecule epigenetic-silencing-inhibitor (ESI1) that enhances myelin production and...
Xuezhao Liu

The epidermal circadian clock integrates and subverts brain signals to guarantee skin homeostasis

3 weeks ago
In mammals, the circadian clock network drives daily rhythms of tissue-specific homeostasis. To dissect daily inter-tissue communication, we constructed a mouse minimal clock network comprising only two nodes: the peripheral epidermal clock and the central brain clock. By transcriptomic and functional characterization of this isolated connection, we identified a gatekeeping function of the peripheral tissue clock with respect to systemic inputs. The epidermal clock concurrently integrates and...
Thomas Mortimer

Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice

3 weeks ago
Many Mendelian developmental disorders caused by coding variants in epigenetic regulators have now been discovered. Epigenetic regulators are broadly expressed, and each of these disorders typically exhibits phenotypic manifestations from many different organ systems. An open question is whether the chromatin disruption - the root of the pathogenesis - is similar in the different disease-relevant cell types. This is possible in principle, since all these cell types are subject to effects from...
Leandros Boukas

Metabolic and neurobehavioral disturbances induced by purine recycling deficiency in <em>Drosophila</em>

3 weeks ago
Adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) are two structurally related enzymes involved in purine recycling in humans. Inherited mutations that suppress HGPRT activity are associated with Lesch-Nyhan disease (LND), a rare X-linked metabolic and neurological disorder in children, characterized by hyperuricemia, dystonia, and compulsive self-injury. To date, no treatment is available for these neurological defects and no animal model...
Céline Petitgas

Early-life exposure to tobacco, genetic susceptibility, and accelerated biological aging in adulthood

3 weeks ago
Early-life tobacco exposure serves as a non-negligible risk factor for aging-related diseases. To understand the underlying mechanisms, we explored the associations of early-life tobacco exposure with accelerated biological aging and further assessed the joint effects of tobacco exposure and genetic susceptibility. Compared with those without in utero exposure, participants with in utero tobacco exposure had an increase in Klemera-Doubal biological age (KDM-BA) and PhenoAge acceleration of 0.26...
Feipeng Cui

Brain-muscle communication prevents muscle aging by maintaining daily physiology

3 weeks 1 day ago
A molecular clock network is crucial for daily physiology and maintaining organismal health. We examined the interactions and importance of intratissue clock networks in muscle tissue maintenance. In arrhythmic mice showing premature aging, we created a basic clock module involving a central and a peripheral (muscle) clock. Reconstituting the brain-muscle clock network is sufficient to preserve fundamental daily homeostatic functions and prevent premature muscle aging. However, achieving whole...
Arun Kumar

Increased intestinal bile acid absorption contributes to age-related cognitive impairment

3 weeks 1 day ago
Cognitive impairment in the elderly is associated with alterations in bile acid (BA) metabolism. In this study, we observe elevated levels of serum conjugated primary bile acids (CPBAs) and ammonia in elderly individuals, mild cognitive impairment, Alzheimer's disease, and aging rodents, with a more pronounced change in females. These changes are correlated with increased expression of the ileal apical sodium-bile acid transporter (ASBT), hippocampal synapse loss, and elevated brain CPBA and...
Zhenxing Ren

Septin 7 interacts with Numb to preserve sarcomere structural organization and muscle contractile function

3 weeks 1 day ago
Here, we investigated the mechanisms by which aging-related reductions of the levels of Numb in skeletal muscle fibers contribute to loss of muscle strength and power, two critical features of sarcopenia. Numb is an adaptor protein best known for its critical roles in development, including asymmetric cell division, cell-type specification, and termination of intracellular signaling. Numb expression is reduced in old humans and mice. We previously showed that, in mouse skeletal muscle fibers,...
Rita De Gasperi

Alterations of human CSF and serum-based mitophagy biomarkers in the continuum of Alzheimer disease

3 weeks 1 day ago
Defective mitophagy is consistently found in postmortem brain and iPSC-derived neurons from Alzheimer disease (AD) patients. However, there is a lack of extensive examination of mitophagy status in serum or cerebrospinal fluid (CSF), and the clinical potential of mitophagy biomarkers has not been tested. We quantified biomarkers of mitophagy/autophagy and lysosomal degradation (PINK1, BNIP3L and TFEB) in CSF and serum from 246 individuals, covering mild cognitive impairment due to AD (MCI-AD, n...
Kateřina Veverová

Vaccination for healthy aging

3 weeks 2 days ago
As the world's population grows older, vaccination is becoming a key strategy for promoting healthy aging. Despite scientific progress in adult vaccine development, obstacles such as immunosenescence and vaccine hesitancy remain. To unlock the potential of adult vaccines fully, we must enhance immunization programs, dispel misinformation, and invest in research that deepens our understanding of aging and immunity.
David E Bloom

Cellular senescence is a double-edged sword in regulating aged immune responses to influenza

3 weeks 2 days ago
Clearance of senescent cells has demonstrated therapeutic potential in the context of chronic age-related diseases. Little is known, however, how clearing senescent cells affects the ability to respond to an acute infection and form quality immunological memory. We aimed to probe the effects of clearing senescent cells in aged mice on the immune response to influenza (flu) infection. We utilized a p16 trimodality reporter mouse model (p16-3MR) to allow for identification and selective clearance...
Blake L Torrance

Cost-effectiveness and cost-utility of a digital technology-driven hierarchical healthcare screening pattern in China

3 weeks 3 days ago
Utilization of digital technologies for cataract screening in primary care is a potential solution for addressing the dilemma between the growing aging population and unequally distributed resources. Here, we propose a digital technology-driven hierarchical screening (DH screening) pattern implemented in China to promote the equity and accessibility of healthcare. It consists of home-based mobile artificial intelligence (AI) screening, community-based AI diagnosis, and referral to hospitals. We...
Xiaohang Wu

Correlates of protection against symptomatic SARS-CoV-2 in vaccinated children

3 weeks 3 days ago
The paucity of information on longevity of vaccine-induced immune responses and uncertainty of the correlates of protection hinder the development of evidence-based COVID-19 vaccination policies for new birth cohorts. Here, to address these knowledge gaps, we conducted a cohort study of healthy 5-12-year-olds vaccinated with BNT162b2. We serially measured binding and neutralizing antibody titers (nAbs), spike-specific memory B cell (MBC) and spike-reactive T cell responses over 1 year. We found...
Youjia Zhong

Fundamentals of redox regulation in biology

3 weeks 3 days ago
Oxidation-reduction (redox) reactions are central to the existence of life. Reactive species of oxygen, nitrogen and sulfur mediate redox control of a wide range of essential cellular processes. Yet, excessive levels of oxidants are associated with ageing and many diseases, including cardiological and neurodegenerative diseases, and cancer. Hence, maintaining the fine-tuned steady-state balance of reactive species production and removal is essential. Here, we discuss new insights into the...
Helmut Sies

PD1 blockade improves survival and CD8<sup>+</sup> cytotoxic capacity, without increasing inflammation, during normal microbial experience in old mice

3 weeks 3 days ago
By 2030, individuals 65 years of age or older will make up approximately 20% of the world's population¹. Older individuals are at the highest risk for mortality from infections, largely due to the pro-inflammatory, dysfunctional immune response, which is collectively known as immunosenescence². During aging, CD8^(+) T cells acquire an exhausted phenotype, including increased expression of inhibitory receptors, such as programmed cell death 1 (PD1), a decline in effector function and elevated...
Korbyn J V Dahlquist

Doxycycline decelerates aging in progeria mice

3 weeks 3 days ago
Beyond the antimicrobial activity, doxycycline (DOX) exhibits longevity-promoting effect in nematodes, while its effect on mammals is unclear. Here, we applied a mouse model of Hutchinson-Gilford progeria syndrome (HGPS), Zmpste24 knockout (KO) mice, and analyzed the antiaging effect of DOX. We found that the DOX treatment prolongs lifespan and ameliorates progeroid features of Zmpste24 KO mice, including the decline of body and tissue weight, exercise capacity and cortical bone density, and the...
Ming Wang
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