Aging, Lifespan & Longevity

Riboflavin depletion promotes longevity and metabolic hormesis in Caenorhabditis elegans

22 hours 54 minutes ago
Riboflavin is an essential cofactor in many enzymatic processes and in the production of flavin adenine dinucleotide (FAD). Here, we report that the partial depletion of riboflavin through knockdown of the C. elegans riboflavin transporter 1 (rft-1) promotes metabolic health by reducing intracellular flavin concentrations. Knockdown of rft-1 significantly increases lifespan in a manner dependent upon AMP-activated protein kinase (AMPK)/aak-2, the mitochondrial unfolded protein response, and...
Armen Yerevanian

Single-cell RNA-seq reveals early heterogeneity during aging in yeast

22 hours 54 minutes ago
The budding yeast Saccharomyces cerevisiae (S. cerevisiae) has relatively short lifespan and is genetically tractable, making it a widely used model organism in aging research. Here, we carried out a systematic and quantitative investigation of yeast aging with single-cell resolution through transcriptomic sequencing. We optimized a single-cell RNA sequencing (scRNA-seq) protocol to quantitatively study the whole transcriptome profiles of single yeast cells at different ages, finding increased...
Jincheng Wang

Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice

1 day 22 hours ago
Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)-1,3-butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, or the combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led to a longer lifespan than in either of the two prior cohorts of mice treated with Rapa only,...
Randy Strong

Meiotic dysfunction accelerates somatic aging in Caenorhabditis elegans

1 day 22 hours ago
An expanding body of evidence, from studies in model organisms to human clinical data, reveals that reproductive health influences organismal aging. However, the impact of germline integrity on somatic aging is poorly understood. Moreover, assessing the causal relationship of such an impact is challenging to address in human and vertebrate models. Here, we demonstrate that disruption of meiosis, a germline restricted process, shortened lifespan, impaired individual aspects of healthspan, and...
Julia A Loose

Protein structural transitions critically transform the network connectivity and viscoelasticity of RNA-binding protein condensates but RNA can prevent it

2 days 22 hours ago
Biomolecular condensates, some of which are liquid-like during health, can age over time becoming gel-like pathological systems. One potential source of loss of liquid-like properties during ageing of RNA-binding protein condensates is the progressive formation of inter-protein β-sheets. To bridge microscopic understanding between accumulation of inter-protein β-sheets over time and the modulation of FUS and hnRNPA1 condensate viscoelasticity, we develop a multiscale simulation approach. Our...
Andres R Tejedor

Exploration of nuclear body-enhanced sumoylation reveals that PML represses 2-cell features of embryonic stem cells

2 days 22 hours ago
Membrane-less organelles are condensates formed by phase separation whose functions often remain enigmatic. Upon oxidative stress, PML scaffolds Nuclear Bodies (NBs) to regulate senescence or metabolic adaptation. PML NBs recruit many partner proteins, but the actual biochemical mechanism underlying their pleiotropic functions remains elusive. Similarly, PML role in embryonic stem cell (ESC) and retro-element biology is unsettled. Here we demonstrate that PML is essential for oxidative...
Sarah Tessier

Mistakes in terminology cause false conclusions: Vitamin D does not increase the risk of dementia

2 days 22 hours ago
There has been a progressive trend in recent years, to trivialize the terminology surrounding the molecules based on a secosteroid structure. The generic use of the term, "vitamin D," results in gross misrepresentations that confuse the use of a drug commonly used for patients with kidney failure, with the nutritional use of vitamin D. This commentary is a critique of one particularly bad example of that terminological trivialization. Authors may simply want to add impact to their findings when...
Reinhold Vieth

Sex- and age-dependent genetics of longevity in a heterogeneous mouse population

2 days 22 hours ago
DNA variants that modulate life span provide insight into determinants of health, disease, and aging. Through analyses in the UM-HET3 mice of the Interventions Testing Program (ITP), we detected a sex-independent quantitative trait locus (QTL) on chromosome 12 and identified sex-specific QTLs, some of which we detected only in older mice. Similar relations between life history and longevity were uncovered in mice and humans, underscoring the importance of early access to nutrients and early...
Maroun Bou Sleiman

Experimental and real-world evidence supporting the computational repurposing of bumetanide for <em>APOE4</em>-related Alzheimer's disease

2 days 22 hours ago
The evident genetic, pathological, and clinical heterogeneity of Alzheimer's disease (AD) poses challenges for traditional drug development. We conducted a computational drug repurposing screen for drugs to treat apolipoprotein (apo) E4-related AD. We first established apoE-genotype-dependent transcriptomic signatures of AD by analyzing publicly-available human brain database. We then queried these signatures against the Connectivity Map database containing transcriptomic perturbations of >1300...
Alice Taubes

The three-dimensional landscape of cortical chromatin accessibility in Alzheimer's disease

3 days 22 hours ago
To characterize the dysregulation of chromatin accessibility in Alzheimer's disease (AD), we generated 636 ATAC-seq libraries from neuronal and nonneuronal nuclei isolated from the superior temporal gyrus and entorhinal cortex of 153 AD cases and 56 controls. By analyzing a total of ~20 billion read pairs, we expanded the repertoire of known open chromatin regions (OCRs) in the human brain and identified cell-type-specific enhancer-promoter interactions. We show that interindividual variability...
Jaroslav Bendl

Prevention of ribosome collision-induced neuromuscular degeneration by SARS CoV-2-encoded Nsp1

3 days 22 hours ago
An overarching goal of aging and age-related neurodegenerative disease research is to discover effective therapeutic strategies applicable to a broad spectrum of neurodegenerative diseases. Little is known about the extent to which targetable pathogenic mechanisms are shared among these seemingly diverse diseases. Translational control is critical for maintaining proteostasis during aging. Gaining control of the translation machinery is also crucial in the battle between viruses and their hosts....
Xingjun Wang

Insulin sensitivity in mesolimbic pathways predicts and improves with weight loss in older dieters

3 days 22 hours ago
Central insulin is critically involved in the regulation of hedonic feeding. Insulin resistance in overweight has recently been shown to reduce the inhibitory function of insulin in the human brain. How this relates to effective weight management is unclear, especially in older people, who are highly vulnerable to hyperinsulinemia and in whom neural target systems of insulin action undergo age-related changes. Here, 50 overweight, non-diabetic older adults participated in a double-blind,...
Lena J Tiedemann

Reprograming of proteasomal degradation by branched chain amino acid metabolism

3 days 22 hours ago
Branched-chain amino acid (BCAA) metabolism is a central hub for energy production and regulation of numerous physiological processes. Controversially, both increased and decreased levels of BCAAs are associated with longevity. Using genetics and multi-omics analyses in Caenorhabditis elegans, we identified adaptive regulation of the ubiquitin-proteasome system (UPS) in response to defective BCAA catabolic reactions after the initial transamination step. Worms with impaired BCAA metabolism show...
Sonia Ravanelli

Bmi1 suppresses protein synthesis and promotes proteostasis in hematopoietic stem cells

4 days 22 hours ago
The polycomb complex component Bmi1 promotes the maintenance of stem cells in multiple postnatal tissues, partly by negatively regulating the expression of p16^(Ink4a) and p19^(Arf), tumor suppressors associated with cellular senescence. However, deficiency for p16^(Ink4a) and p19^(Arf) only partially rescues the function of Bmi1-deficient stem cells. We conditionally deleted Bmi1 from adult hematopoietic cells and found that this slowly depleted hematopoietic stem cells (HSCs). Rather than...
Rebecca J Burgess

Rejuvenation of the aged brain immune cell landscape in mice through p16-positive senescent cell clearance

4 days 22 hours ago
Cellular senescence is a plausible mediator of inflammation-related tissue dysfunction. In the aged brain, senescent cell identities and the mechanisms by which they exert adverse influence are unclear. Here we used high-dimensional molecular profiling, coupled with mechanistic experiments, to study the properties of senescent cells in the aged mouse brain. We show that senescence and inflammatory expression profiles increase with age and are brain region- and sex-specific. p16-positive myeloid...
Xu Zhang

Single-cell analysis reveals transcriptomic reprogramming in aging primate entorhinal cortex and the relevance with Alzheimer's disease

4 days 22 hours ago
The entorhinal cortex is of great importance in cognition and memory, its dysfunction causes a variety of neurological diseases, particularly Alzheimer's disease (AD). Yet so far, research on entorhinal cortex is still limited. Here, we provided the first single-nucleus transcriptomic map of primate entorhinal cortex aging. Our result revealed that synapse signaling, neurogenesis, cellular homeostasis, and inflammation-related genes and pathways changed in a cell-type-specific manner with age....
Ming-Li Li
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