Aging, Lifespan & Longevity

Metabolic consequences of obesity and type 2 diabetes: balancing genes and environment for personalized care

1 day 7 hours ago
The prevalence of type 2 diabetes and obesity has risen dramatically for decades and is expected to rise further, secondary to the growing aging, sedentary population. The strain on global health care is projected to be colossal. This review explores the latest work and emerging ideas related to genetic and environmental factors influencing metabolism. Translational research and clinical applications, including the impact of the COVID-19 pandemic, are highlighted. Looking forward, strategies to...
Nicolas J Pillon

Role of the DNAJ/HSP40 family in the pathogenesis of insulin resistance and type 2 diabetes

1 day 7 hours ago
Insulin resistance (IR) underpins a wide range of metabolic disorders including type 2 diabetes (T2D), metabolic syndrome and cardiovascular diseases. IR is characterized by a marked reduction in the magnitude and/or delayed onset of insulin to stimulate glucose disposal. This condition is due to defects in one or several intracellular intermediates of the insulin signaling cascade, ranging from insulin receptor substrate (IRS) inactivation to reduced glucose phosphorylation and oxidation....
Abdoulaye Diane

Astrocyte dystrophy in ageing brain parallels impaired synaptic plasticity

1 day 7 hours ago
Little is known about age-dependent changes in structure and function of astrocytes and of the impact of these on the cognitive decline in the senescent brain. The prevalent view on the age-dependent increase in reactive astrogliosis and astrocytic hypertrophy requires scrutiny and detailed analysis. Using two-photon microscopy in conjunction with 3D reconstruction, Sholl and volume fraction analysis, we demonstrate a significant reduction in the number and the length of astrocytic processes, in...
Alexander Popov

Comment on "Increased growing-season productivity drives earlier autumn leaf senescence in temperate trees"

1 day 7 hours ago
Zani et al (Research Articles, 27 November 2020, p. 1066) propose that enhancement of deciduous tree photosynthesis in a CO(2)-enriched atmosphere will advance autumn leaf senescence. This premise is not supported by consistent observations from free-air CO(2) enrichment (FACE) experiments. In most FACE experiments, leaf senescence or abscission was not altered or was delayed in trees exposed to elevated CO(2).
Richard J Norby

Response to Comment on "Increased growing-season productivity drives earlier autumn leaf senescence in temperate trees"

1 day 7 hours ago
Our study showed that increases in seasonal productivity drive earlier autumn senescence of temperate trees. Norby argues that this finding is contradicted by observations from free-air CO(2) enrichment (FACE) experiments, where elevated CO(2) has been found to delay senescence in some cases. We provide a detailed answer showing that the results from FACE studies are in agreement with our conclusions.
Deborah Zani

The ketogenic diet preserves skeletal muscle with aging in mice

1 day 7 hours ago
The causes of the decline in skeletal muscle mass and function with age, known as sarcopenia, are poorly understood. Nutrition (calorie restriction) interventions impact many cellular processes and increase lifespan and preserve muscle mass and function with age. As we previously observed an increase in life span and muscle function in aging mice on a ketogenic diet (KD), we aimed to investigate the effect of a KD on the maintenance of skeletal muscle mass with age and the potential molecular...
Marita A Wallace

Functional genomic analyses highlight a shift in Gpr17-regulated cellular processes in oligodendrocyte progenitor cells and underlying myelin dysregulation in the aged mouse cerebrum

1 day 7 hours ago
Brain ageing is characterised by a decline in neuronal function and associated cognitive deficits. There is increasing evidence that myelin disruption is an important factor that contributes to the age-related loss of brain plasticity and repair responses. In the brain, myelin is produced by oligodendrocytes, which are generated throughout life by oligodendrocyte progenitor cells (OPCs). Currently, a leading hypothesis points to ageing as a major reason for the ultimate breakdown of...
Andrea D Rivera

Alzheimer's disease

2 days 7 hours ago
In this Seminar, we highlight the main developments in the field of Alzheimer's disease. The most recent data indicate that, by 2050, the prevalence of dementia will double in Europe and triple worldwide, and that estimate is 3 times higher when based on a biological (rather than clinical) definition of Alzheimer's disease. The earliest phase of Alzheimer's disease (cellular phase) happens in parallel with accumulating amyloid β, inducing the spread of tau pathology. The risk of Alzheimer's...
Philip Scheltens

Reduced insulin/IGF1 signaling prevents immune aging via ZIP-10/bZIP-mediated feedforward loop

2 days 7 hours ago
A hallmark of aging is immunosenescence, a decline in immune functions, which appeared to be inevitable in living organisms, including Caenorhabditis elegans. Here, we show that genetic inhibition of the DAF-2/insulin/IGF-1 receptor drastically enhances immunocompetence in old age in C. elegans. We demonstrate that longevity-promoting DAF-16/FOXO and heat-shock transcription factor 1 (HSF-1) increase immunocompetence in old daf-2(-) animals. In contrast, p38 mitogen-activated protein kinase 1...
Yujin Lee

<em>Mayday</em> sustains trans-synaptic BMP signaling required for synaptic maintenance with age

2 days 7 hours ago
Maintaining synaptic structure and function over time is vital for overall nervous system function and survival. The processes that underly synaptic development are well understood. However, the mechanisms responsible for sustaining synapses throughout the lifespan of an organism are poorly understood. Here, we demonstrate that a previously uncharacterized gene, CG31475, regulates synaptic maintenance in adult Drosophila NMJs. We named CG31475 mayday due to the progressive loss of flight ability...
Jessica M Sidisky

Fine-tuning p53 activity by modulating the interaction between eukaryotic translation initiation factor eIF4E and RNA-binding protein RBM38

2 days 7 hours ago
p53 is critical for tumor suppression but also elicits detrimental effects when aberrantly overexpressed. Thus, multiple regulators, including RNA-binding protein RBM38, are found to tightly control p53 expression. Interestingly, RBM38 is unique in that it can either suppress or enhance p53 mRNA translation via altered interaction with eIF4E potentially mediated by serine-195 (S195) in RBM38. Thus, multiple RBM38/eIF4E knock-in (KI) cell lines were generated to investigate the significance of...
Wenqiang Sun

Cardiovascular disease risk factors induce mesenchymal features and senescence in mouse cardiac endothelial cells

3 days 7 hours ago
Aging, obesity, hypertension and physical inactivity are major risk factors for endothelial dysfunction and cardiovascular disease (CVD). We applied fluorescence-activated cell sorting (FACS), RNA sequencing and bioinformatic methods to investigate the common effects of CVD risk factors in mouse cardiac endothelial cells (ECs). Aging, obesity and pressure overload all upregulated pathways related to TGF-b signaling and mesenchymal gene expression, inflammation, vascular permeability, oxidative...
Karthik Amudhala Hemanthakumar

Barrier-to-autointegration-factor (Banf1) modulates DNA double-strand break repair pathway choice via regulation of DNA-dependent kinase (DNA-PK) activity

3 days 7 hours ago
DNA repair pathways are essential to maintain the integrity of the genome and prevent cell death and tumourigenesis. Here, we show that the Barrier-to-Autointegration Factor (Banf1) protein has a role in the repair of DNA double-strand breaks. Banf1 is characterized as a nuclear envelope protein and mutations in Banf1 are associated with the severe premature aging syndrome, Néstor-Guillermo Progeria Syndrome. We have previously shown that Banf1 directly regulates the activity of PARP1 in the...
Joshua T Burgess

Antagonistic control of myofiber size and muscle protein quality control by the ubiquitin ligase UBR4 during aging

3 days 7 hours ago
Sarcopenia is a degenerative condition that consists in age-induced atrophy and functional decline of skeletal muscle cells (myofibers). A common hypothesis is that inducing myofiber hypertrophy should also reinstate myofiber contractile function but such model has not been extensively tested. Here, we find that the levels of the ubiquitin ligase UBR4 increase in skeletal muscle with aging, and that UBR4 increases the proteolytic activity of the proteasome. Importantly, muscle-specific UBR4 loss...
Liam C Hunt

A novel p53 regulator, C16ORF72/TAPR1, buffers against telomerase inhibition

3 days 7 hours ago
Telomere erosion in cells with insufficient levels of the telomerase reverse transcriptase (TERT), contributes to age-associated tissue dysfunction and senescence, and p53 plays a crucial role in this response. We undertook a genome-wide CRISPR screen to identify gene deletions that sensitized p53-positive human cells to telomerase inhibition. We uncovered a previously unannotated gene, C16ORF72, which we term Telomere Attrition and p53 Response 1 (TAPR1), that exhibited a synthetic-sick...
Yahya Benslimane

Keep your macrophages fit for healthy aging

4 days 7 hours ago
As age is the greatest risk factor for the development of most prevalent chronic diseases, there is an enormous interest in understanding the process of aging, with the hope of delaying or preventing age-related comorbidities. Along these lines, a recent study by Minhas et al. (2021) describes how aged macrophages downregulate glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), inducing an energy-deficient state that compromises macrophage function and supports maladaptive...
Jan Van den Bossche

Hallmarks of environmental insults

4 days 7 hours ago
Environmental insults impair human health around the world. Contaminated air, water, soil, food, and occupational and household settings expose humans of all ages to a plethora of chemicals and environmental stressors. We propose eight hallmarks of environmental insults that jointly underpin the damaging impact of environmental exposures during the lifespan. Specifically, they include oxidative stress and inflammation, genomic alterations and mutations, epigenetic alterations, mitochondrial...
Annette Peters

Development, maturation, and maintenance of human prostate inferred from somatic mutations

4 days 7 hours ago
Clonal dynamics and mutation burden in healthy human prostate epithelium are relevant to prostate cancer. We sequenced whole genomes from 409 microdissections of normal prostate epithelium across 8 donors, using phylogenetic reconstruction with spatial mapping in a 59-year-old man's prostate to reconstruct tissue dynamics across the lifespan. Somatic mutations accumulate steadily at ∼16 mutations/year/clone, with higher rates in peripheral than peri-urethral regions. The 24-30 independent...
Sebastian Grossmann

Epigenetic enzymes: A role in aging and prospects for pharmacological targeting

4 days 7 hours ago
The development of interventions aimed at improving healthspan is one of the priority tasks for the academic and public health authorities. It is also the main objective of a novel branch in biogerontological research, geroscience. According to the geroscience concept, targeting aging is an effective way to combat age-related disorders. Since aging is an exceptionally complex process, system-oriented integrated approaches seem most appropriate for such an interventional strategy. Given the high...
Elena G Pasyukova
3 hours 45 minutes ago
Aging, Lifespan & Longevity
(Rejuvenation[TitleAbstract] OR Rejuvenate[TitleAbstract] OR Senescent[TitleAbstract] OR Senescence[TitleAbstract] OR Aging[TitleAbstract] OR Ageing[TitleAbstract] OR Lifespan[TitleAbstract] O…: Latest results from PubMed
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