Aging, Lifespan & Longevity

The effects of graded calorie restriction XVII: Multitissue metabolomics reveals synthesis of carnitine and NAD, and tRNA charging as key pathways

14 hours 47 minutes ago
The evolutionary context of why caloric restriction (CR) activates physiological mechanisms that slow the process of aging remains unclear. The main goal of this analysis was to identify, using metabolomics, the common pathways that are modulated across multiple tissues (brown adipose tissue, liver, plasma, and brain) to evaluate two alternative evolutionary models: the "disposable soma" and "clean cupboards" ideas. Across the four tissues, we identified more than 10,000 different metabolic...
Libia Alejandra García-Flores

Endo-lysosomal Aβ concentration and pH trigger formation of Aβ oligomers that potently induce Tau missorting

14 hours 47 minutes ago
Amyloid-β peptide (Aβ) forms metastable oligomers >50 kDa, termed AβOs, that are more effective than Aβ amyloid fibrils at triggering Alzheimer's disease-related processes such as synaptic dysfunction and Tau pathology, including Tau mislocalization. In neurons, Aβ accumulates in endo-lysosomal vesicles at low pH. Here, we show that the rate of AβO assembly is accelerated 8,000-fold upon pH reduction from extracellular to endo-lysosomal pH, at the expense of amyloid fibril formation. The...
Marie P Schützmann

Decreased antiviral immune response within the central nervous system of aged mice is associated with increased lethality of West Nile virus encephalitis

1 day 14 hours ago
West Nile virus (WNV) is an emerging pathogen that causes disease syndromes ranging from a mild flu-like illness to encephalitis. While the incidence of WNV infection is fairly uniform across age groups, the risk of lethal encephalitis increases with advanced age. Prior studies have demonstrated age-related, functional immune deficits that limit systemic antiviral immunity and increase mortality; however, the effect of age on antiviral immune responses specifically within the central nervous...
Kristen E Funk

The intrinsic chaperone network of Arabidopsis stem cells confers protection against proteotoxic stress

1 day 14 hours ago
The biological purpose of plant stem cells is to maintain themselves while providing new pools of differentiated cells that form organs and rejuvenate or replace damaged tissues. Protein homeostasis or proteostasis is required for cell function and viability. However, the link between proteostasis and plant stem cell identity remains unknown. In contrast to their differentiated counterparts, we find that root stem cells can prevent the accumulation of aggregated proteins even under proteotoxic...
Ernesto Llamas

Counteracting age-related VEGF signaling insufficiency promotes healthy aging and extends life span

1 day 14 hours ago
Aging is an established risk factor for vascular diseases, but vascular aging itself may contribute to the progressive deterioration of organ function. Here, we show in aged mice that vascular endothelial growth factor (VEGF) signaling insufficiency, which is caused by increased production of decoy receptors, may drive physiological aging across multiple organ systems. Increasing VEGF signaling prevented age-associated capillary loss, improved organ perfusion and function, and extended life...
M Grunewald

The p53 transcriptional response across tumor types reveals core and senescence-specific signatures modulated by long noncoding RNAs

1 day 14 hours ago
The p53 pathway is a universal tumor suppressor mechanism that limits tumor progression by triggering apoptosis or permanent cell cycle arrest, called senescence. In recent years, efforts to reactivate p53 function in cancer have proven to be a successful therapeutic strategy in murine models and have gained traction with the development of a range of small molecules targeting mutant p53. However, knowledge of the downstream mediators of p53 reactivation in different oncogenic contexts has been...
Ephrath Tesfaye

Photobiomodulation for the aging brain

2 days 14 hours ago
Longevity is one of the great triumphs of humanity. Worldwide, the elderly is the fastest growing segment of the population. As a consequence, the number of cases of age-related cognitive decline and neurological diseases associated with aging, such as Alzheimer's and Parkinson's, has been increasing. Among the non-pharmacological interventions studied for the treatment or prevention of age-related neurocognitive impairment, photobiomodulation (PBM) has gained prominence for its beneficial...
Fabrízio Dos Santos Cardoso

Olfactory dysfunction in aging and neurodegenerative diseases

2 days 14 hours ago
Alterations in olfactory functions are proposed to be early biomarkers for neurodegeneration. Many neurodegenerative diseases are age-related, including two of the most common, Parkinson's disease (PD) and Alzheimer's disease (AD). The establishment of biomarkers that promote early risk identification is critical for the implementation of early treatment to postpone or avert pathological development. Olfactory dysfunction (OD) is seen in 90% of early-stage PD patients and 85% of patients with...
Xiuli Dan

Lipocalin 2 as a link between ageing, risk factor conditions and age-related brain diseases

2 days 14 hours ago
Chronic (neuro)inflammation plays an important role in many age-related central nervous system (CNS) diseases, including Alzheimer's disease, Parkinson's disease and vascular dementia. Inflammation also characterizes many conditions that form a risk factor for these CNS disorders, such as physical inactivity, obesity and cardiovascular disease. Lipocalin 2 (Lcn2) is an inflammatory protein shown to be involved in different age-related CNS diseases, as well as risk factor conditions thereof. Lcn2...
Doortje W Dekens

Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians

2 days 14 hours ago
Centenarians display decreased susceptibility to ageing-associated illness, chronic inflammation, and infectious disease^(1-3). Here we show that centenarians have a distinct gut microbiome enriched in microbes capable of generating unique secondary bile acids (BAs), including iso-, 3-oxo-, allo-, 3-oxoallo-, and isoallo-lithocholic acid (LCA). Among these BAs, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from a centenarian's...
Yuko Sato

An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis

2 days 14 hours ago
Synaptic membrane-remodeling events such as endocytosis require force-generating actin assembly. The endocytic machinery that regulates these actin and membrane dynamics localizes at high concentrations to large areas of the presynaptic membrane, but actin assembly and productive endocytosis are far more restricted in space and time. Here we describe a mechanism whereby autoinhibition clamps the presynaptic endocytic machinery to limit actin assembly to discrete functional events. We found that...
Steven J Del Signore

Rewiring of the ubiquitinated proteome determines ageing in C. elegans

2 days 14 hours ago
Ageing is driven by a loss of cellular integrity¹. Given the major role of ubiquitin modifications in cell function², here we assess the link between ubiquitination and ageing by quantifying whole-proteome ubiquitin signatures in Caenorhabditis elegans. We find a remodelling of the ubiquitinated proteome during ageing, which is ameliorated by longevity paradigms such as dietary restriction and reduced insulin signalling. Notably, ageing causes a global loss of ubiquitination that is triggered by...
Seda Koyuncu

Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging

2 days 14 hours ago
During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function impacting mobility and quality of life. Muscle loss is often associated with denervation and a loss of resident muscle stem cells (satellite cells or MuSCs), however, the relationship between MuSCs and innervation has not been established. Herein, we administered severe neuromuscular trauma to a transgenic murine model that permits MuSC lineage tracing. We show that a subset of MuSCs...
Jacqueline Larouche

Insulin signaling regulates longevity through protein phosphorylation in Caenorhabditis elegans

3 days 14 hours ago
Insulin/IGF-1 Signaling (IIS) is known to constrain longevity by inhibiting the transcription factor FOXO. How phosphorylation mediated by IIS kinases regulates lifespan beyond FOXO remains unclear. Here, we profile IIS-dependent phosphorylation changes in a large-scale quantitative phosphoproteomic analysis of wild-type and three IIS mutant Caenorhabditis elegans strains. We quantify more than 15,000 phosphosites and find that 476 of these are differentially phosphorylated in the long-lived...
Wen-Jun Li

Oncogene-induced senescence in hematopoietic progenitors features myeloid restricted hematopoiesis, chronic inflammation and histiocytosis

3 days 14 hours ago
Activating mutations in the BRAF-MAPK pathway have been reported in histiocytoses, hematological inflammatory neoplasms characterized by multi-organ dissemination of pro-inflammatory myeloid cells. Here, we generate a humanized mouse model of transplantation of human hematopoietic stem and progenitor cells (HSPCs) expressing the activated form of BRAF (BRAF^(V600E)). All mice transplanted with BRAF^(V600E)-expressing HSPCs succumb to bone marrow failure, displaying myeloid-restricted...
Riccardo Biavasco

All cells are created equal in the sight of autophagy: selective autophagy maintains homeostasis in senescent cells

4 days 14 hours ago
Macroautophagy/autophagy is a sophisticated quality control program that limits cellular damage and maintains homeostasis, being an essential part of several lifespan-promoting interventions. However, autophagy is also necessary for full establishment of cellular senescence, a causal factor for many age-related diseases and aging. What lies ahead of us to unravel such a paradoxical role of autophagy in senescence is to identify specific targets degraded by autophagy during senescence and...
Jaejin Kim
3 hours 46 minutes ago
Aging, Lifespan & Longevity
Aging: Latest results from PubMed
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