Aging, Lifespan & Longevity

Induction of somatopause in adult mice compromises bone morphology and exacerbates bone loss during aging

5 days 20 hours ago
Somatopause refers to the gradual declines in growth hormone (GH) and insulin-like growth factor-1 throughout aging. To define how induced somatopause affects skeletal integrity, we used an inducible GH receptor knockout (iGHRKO) mouse model. Somatopause, induced globally at 6 months of age, resulted in significantly more slender bones in both male and female iGHRKO mice. In males, induced somatopause was associated with progressive expansion of the marrow cavity leading to significant thinning...
Manisha Dixit

BRAF<sup>V600E</sup> induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB

5 days 20 hours ago
Benign melanocytic nevi frequently emerge when an acquired BRAF^(V600E) mutation triggers unchecked proliferation and subsequent arrest in melanocytes. Recent observations have challenged the role of oncogene-induced senescence in melanocytic nevus formation, necessitating investigations into alternative mechanisms for the establishment and maintenance of proliferation arrest in nevi. We compared the transcriptomes of melanocytes from healthy human skin, nevi, and melanomas arising from nevi and...
Andrew S McNeal

The active grandparent hypothesis: Physical activity and the evolution of extended human healthspans and lifespans

5 days 20 hours ago
The proximate mechanisms by which physical activity (PA) slows senescence and decreases morbidity and mortality have been extensively documented. However, we lack an ultimate, evolutionary explanation for why lifelong PA, particularly during middle and older age, promotes health. As the growing worldwide epidemic of physical inactivity accelerates the prevalence of noncommunicable diseases among aging populations, integrating evolutionary and biomedical perspectives can foster new insights into...
Daniel E Lieberman

Dissociable effects of <em>APOE</em>-ε4 and β-amyloid pathology on visual working memory

6 days 20 hours ago
Although APOE-ε4 carriers are at significantly higher risk of developing Alzheimer's disease than non-carriers¹, controversial evidence suggests that APOE-ε4 might confer some advantages, explaining the survival of this gene (antagonistic pleiotropy)^(2,3). In a population-based cohort born in one week in 1946 (assessed aged 69-71), we assessed differential effects of APOE-ε4 and β-amyloid pathology (quantified using ^(18)F-Florbetapir-PET) on visual working memory (object-location binding). In...
Kirsty Lu

BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities

1 week 1 day ago
Nicotinamide riboside (NR) is one of the orally bioavailable NAD^(+) precursors and has been demonstrated to exhibit beneficial effects against aging and aging-associated diseases. However, the metabolic pathway of NR in vivo is not yet fully understood. Here, we demonstrate that orally administered NR increases NAD^(+) level via two different pathways. In the early phase, NR was directly absorbed and contributed to NAD^(+) generation through the NR salvage pathway, while in the late phase, NR...
Keisuke Yaku

A national cohort study (2000-2018) of long-term air pollution exposure and incident dementia in older adults in the United States

1 week 1 day ago
Air pollution may increase risk of Alzheimer's disease and related dementias (ADRD) in the U.S., but the extent of this relationship is unclear. Here, we constructed two national U.S. population-based cohorts of those aged ≥65 from the Medicare Chronic Conditions Warehouse (2000-2018), combined with high-resolution air pollution datasets, to investigate the association of long-term exposure to ambient fine particulate matter (PM(2.5)), nitrogen dioxide (NO(2)), and ozone (O(3)) with dementia and...
Liuhua Shi

Mitochondrial aconitase 1 regulates age-related memory impairment via autophagy/mitophagy-mediated neural plasticity in middle-aged flies

1 week 1 day ago
Age-related memory impairment (AMI) occurs in many species, including humans. The underlying mechanisms are not fully understood. In wild-type Drosophila (w^(1118) ), AMI appears in the form of a decrease in learning (3-min memory) from middle age (30 days after eclosion [DAE]). We performed in vivo, DNA microarray, and behavioral screen studies to identify genes controlling both lifespan and AMI and selected mitochondrial Acon1 (mAcon1). mAcon1 expression in the head of w^(1118) decreased with...
Yun-Ho Cho

alpha-Synuclein antisense transcript SNCA-AS1 regulates synapses- and aging-related genes suggesting its implication in Parkinson's disease

1 week 1 day ago
SNCA protein product, α-synuclein, is widely renowned for its role in synaptogenesis and implication in both aging and Parkinson's disease (PD), but research efforts are still needed to elucidate its physiological functions and mechanisms of regulation. In this work, we aim to characterize SNCA-AS1, antisense transcript to the SNCA gene, and its implications in cellular processes. The overexpression of SNCA-AS1 upregulates both SNCA and α-synuclein and, through RNA-sequencing analysis, we...
Federica Rey

Cryo-EM reveals mechanistic insights into lipid-facilitated polyamine export by human ATP13A2

1 week 2 days ago
The cytoplasmic polyamine maintains cellular homeostasis by chelating toxic metal cations, regulating transcriptional activity, and protecting DNA. ATP13A2 was identified as a lysosomal polyamine exporter responsible for polyamine release into the cytosol, and its dysfunction is associated with Alzheimer's disease and other neural degradation diseases. ATP13A2 belongs to the P5 subfamily of the P-type ATPase family, but its mechanisms remain unknown. Here, we report the cryoelectron microscopy...
Atsuhiro Tomita

Formaldehyde toxicity in age-related neurological dementia

1 week 2 days ago
The primordial small gaseous molecules, such as: NO, CO, H(2)S and formaldehyde (FA) are present in the brains. Whether FA as well as the other molecules participates in brain functions is unclear. Recently, its pathophysiological functions have been investigated. Notably, under physiological conditions, learning activity induces a transient generation of hippocampal FA, which promotes memory formation by enhancing N-methyl-D-aspartate (NMDA)-currents. However, ageing leads to FA accumulation in...
Yiduo Kou

Altered cell and RNA isoform diversity in aging Down syndrome brains

1 week 2 days ago
Down syndrome (DS), trisomy of human chromosome 21 (HSA21), is characterized by lifelong cognitive impairments and the development of the neuropathological hallmarks of Alzheimer's disease (AD). The cellular and molecular modifications responsible for these effects are not understood. Here we performed single-nucleus RNA sequencing (snRNA-seq) employing both short- (Illumina) and long-read (Pacific Biosciences) sequencing technologies on a total of 29 DS and non-DS control prefrontal cortex...
Carter R Palmer

Mapping protein carboxymethylation sites provides insights into their role in proteostasis and cell proliferation

1 week 2 days ago
Posttranslational mechanisms play a key role in modifying the abundance and function of cellular proteins. Among these, modification by advanced glycation end products has been shown to accumulate during aging and age-associated diseases but specific protein targets and functional consequences remain largely unexplored. Here, we devise a proteomic strategy to identify sites of carboxymethyllysine modification, one of the most abundant advanced glycation end products. We identify over 1000 sites...
Simone Di Sanzo

Enhanced epigenetic profiling of classical human monocytes reveals a specific signature of healthy aging in the DNA methylome

1 week 2 days ago
The impact of healthy aging on molecular programming of immune cells is poorly understood. Here, we report comprehensive characterization of healthy aging in human classical monocytes, with a focus on epigenomic, transcriptomic, and proteomic alterations, as well as the corresponding proteomic and metabolomic data for plasma, using healthy cohorts of 20 young and 20 older males (~27 and ~64 years old on average). For each individual, we performed eRRBS-based DNA methylation profiling, which...
Irina Shchukina

Sex-specific accelerated decay in time/activity-dependent plasticity and associative memory in an animal model of Alzheimer's disease

1 week 2 days ago
Clinical studies have shown that female brains are more predisposed to neurodegenerative diseases such as Alzheimer's disease (AD), but the cellular and molecular mechanisms behind this disparity remain unknown. In several mouse models of AD, synaptic plasticity dysfunction is an early event and appears before significant accumulation of amyloid plaques and neuronal degeneration. However, it is unclear whether sexual dimorphism at the synaptic level contributes to the higher risk and prevalence...
Sheeja Navakkode

A recurrent chromosomal inversion suffices for driving escape from oncogene-induced senescence via subTAD reorganization

1 week 3 days ago
Oncogene-induced senescence (OIS) is an inherent and important tumor suppressor mechanism. However, if not removed timely via immune surveillance, senescent cells also have detrimental effects. Although this has mostly been attributed to the senescence-associated secretory phenotype (SASP) of these cells, we recently proposed that "escape" from the senescent state is another unfavorable outcome. The mechanism underlying this phenomenon remains elusive. Here, we exploit genomic and functional...
Christos P Zampetidis

Adaptation to hypoxia in <em>Drosophila melanogaster</em> requires autophagy

1 week 3 days ago
Macroautophagy/autophagy, a mechanism of degradation of intracellular material required to sustain cellular homeostasis, is exacerbated under stress conditions like nutrient deprivation, protein aggregation, organelle senescence, pathogen invasion, and hypoxia, among others. Detailed in vivo description of autophagic responses triggered by hypoxia is limited. We have characterized the autophagic response induced by hypoxia in Drosophila melanogaster. We found that this process is essential for...
Ayelén Valko

Observation of universal ageing dynamics in antibiotic persistence

1 week 3 days ago
Stress responses allow cells to adapt to changes in external conditions by activating specific pathways¹. Here we investigate the dynamics of single cells that were subjected to acute stress that is too strong for a regulated response but not lethal. We show that when the growth of bacteria is arrested by acute transient exposure to strong inhibitors, the statistics of their regrowth dynamics can be predicted by a model for the cellular network that ignores most of the details of the underlying...
Yoav Kaplan

Genome-wide analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine at single-nucleotide resolution unveils reduced occurrence of oxidative damage at G-quadruplex sites

1 week 4 days ago
8-Oxo-7,8-dihydro-2'-deoxyguanosine (OG), one of the most common oxidative DNA damages, causes genome instability and is associated with cancer, neurological diseases and aging. In addition, OG and its repair intermediates can regulate gene transcription, and thus play a role in sensing cellular oxidative stress. However, the lack of methods to precisely map OG has hindered the study of its biological roles. Here, we developed a single-nucleotide resolution OG-sequencing method, named CLAPS-seq...
Jiao An
42 minutes 8 seconds ago
Aging, Lifespan & Longevity
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