Aging & Longevity

Liver-derived circulating nicotinamide from nicotinamide adenine dinucleotide (NAD^(+)) catabolism primarily feeds systemic organs for NAD^(+) synthesis. We surprisingly found that, despite blunted hepatic NAD^(+) and nicotinamide production in liver-specific nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) deletion mice (liver-specific knockout [LKO]), circulating nicotinamide and extra-hepatic organs' NAD^(+) are unaffected. Metabolomics reveals a massive accumulation of a novel molecule...

Aging of hematopoietic and immune system (HIS) leads to cellular senescence and immune dysregulation, contributing to age-related diseases. Here, we show that Procyanidin C1 (PCC1), a compound with both senolytic and senomorphic properties, can counteract aging-related changes in HIS. Using single-cell RNA sequencing and validation experiments, we found that aging induced cellular senescence, inflammation, and immune dysregulation in the bone marrow and spleen tissues of mice. Long-term PCC1...

No abstract

Muscle power is a better indicator of musculoskeletal health and functional capacity than muscle strength. The Load-Velocity (L-V) relationship provides a method for assessing muscle function during dynamic multi-joint movements, making it valuable for identifying age-related neuromuscular decline. This study aimed to examine the relationship between variables derived from the L-V relationship (L(0), V(0), and A(line)) obtained during the loaded sit-to-stand test and various muscle performance...

Single-cell transcriptome profiling enables unparalleled characterization of the heterogeneous microenvironment of pediatric leukemias. To facilitate comparative analyses and generate pediatric leukemia signatures, we collect, process, and annotate single-cell data comprising over 540,000 cells from 159 different pediatric acute leukemia (myeloid, lymphoid, mixed phenotype lineages) and healthy bone marrow (BM) samples, profiled in our lab and curated from publicly available studies. The...

CONCLUSION: This study focused on quality of life and factors in older adults with possible sarcopenia or sarcopenia. The research results showed that in order to prevent the decline in the quality of life of older adults with sarcopenia, it is very important to regularly examine the oral health status of the older adults, prevent the occurrence of chronic diseases.Multimodal interventions address common sensory impairments.Carry out aging-friendly renovation of the home environment and conduct...

The locus coeruleus (LC), one of the earliest structures affected by tau pathology in Alzheimer's disease (AD), plays an important role in modulating arousal and learning. In asymptomatic early stages of AD, more sensitive measures to identify subtle cognitive changes are needed. Previous studies indicate that practice effects can signal initial AD-related learning deficits. Here, we assessed the association between LC integrity and practice effects. We combined dedicated LC-MRI methods with...

Anthocyanins are dietary flavonoids shown to have a therapeutic capacity to mitigate inflammation and oxidative stress. The present secondary analyses from the "Anthocyanins in People at Risk for Dementia Study" were aimed at (I) determining the intervention's effect on blood-based markers of cardiovascular disease and inflammation and (II) evaluating whether baseline factors such as age, sex, inflammation, or cardiometabolic score may moderate the intervention's effect on inflammatory status....

The eye lens is a unique tissue optimized for light transmission and refraction, necessitating dissolution of all organelles in mature fiber cells. This absence of organelles prevents protein turnover and leads to the accumulation of many spontaneous modifications over time. One modification that is oft overlooked is isomerization, despite its known impact on protein structure, interference with enzymatic activity, and association with disease. Prior analysis of isomerization in the lens has...

Cells experience oxidative stress and widespread cellular damage during stress-induced premature senescence (SIPS). Senescent cells show an increase in lysosomal content, which may contribute to mitigating cellular damage by promoting autophagy. This study investigates the dynamics of lysosomal quality control in human dermal fibroblasts (HDF), specifically examining lysosomal signaling pathways during oxidative stress-induced SIPS. Our results reveal distinct signaling responses between the...

Aging is associated with a gradual decline in cellular function, largely driven by oxidative stress, which leads to cellular senescence. These processes contribute to tissue degeneration and age-related dysfunction. Human dermal fibroblasts (HDFs), critical for maintaining skin structure, are highly vulnerable to oxidative damage, making them key contributors to skin aging. Umbilical cord blood plasma (UCBP), rich in growth factors and regenerative molecules, has shown potential in preventing...

Microglia and border-associated macrophages (BAMs) are critical for brain health, and their dysfunction is associated to disease. Replacing brain macrophages holds substantial therapeutic promise but remains challenging. Here, we demonstrate that monocytes can efficiently replace all brain macrophages. Monocytes readily replaced embryonal BAMs upon their depletion and engrafted as monocyte-derived microglia (Mo-Microglia) upon more sustained niche availability. Mo-Microglia expanded comparably...

Polymer glasses such as the plastics used in pipes, structural materials, and medical devices are ubiquitous in daily life. The nature of their low molecular mobility is still poorly understood and it leads to brittle mechanical behavior, damage, and fracture over time. It also prevents the design of self-healing mechanisms that expand the material's lifespan, as more commonly done in recent years for higher mobility amorphous polymers such as gels and rubbers. We demonstrate through numerical...

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Decades ago, evidence of age-related reactivation of a single gene on the female inactive X chromosome was observed in mice. While stable silencing of the Barr body is crucial for balancing gene dosage between sexes, it remains unclear whether silencing is maintained during aging. Here we used allele-specific multi-omics approaches to capture a comprehensive catalog of genes escaping X chromosome inactivation throughout mouse development and aging. We found substantially elevated escape rates...

The human gut harbors thousands of microbial species, each exhibiting significant inter-individual genetic variability. Although many studies have associated microbial relative abundances with human-health-related phenotypes, the substantial intraspecies genetic variability of gut microbes has not yet been comprehensively considered, limiting the potential of linking such genetic traits with host conditions. Here, we analyzed 32,152 metagenomes from 94 microbiome studies across the globe to...

Nicotinamide adenine dinucleotide (NAD) is a ubiquitous electron carrier essential for energy metabolism and post-translational modification of numerous regulatory proteins. Dysregulations of NAD metabolism are widely regarded as detrimental to health, with NAD depletion commonly implicated in aging. However, the extent to which cellular NAD concentration can decline without adverse consequences remains unclear. To investigate this, we generated a mouse model in which nicotinamide...

CONCLUSIONS: This study confirms and adds nuance to international findings that overnight hospitalization is associated with accelerated cognitive decline. This association was dose-dependent, had a recency effect and was independent of illness severity in the case of cLOS. These findings suggest that all-cause acute hospitalization may be a reversible risk factor for cognitive decline. This needs further clarification and the development of interventions to minimise the impact of acute illness...

BACKGROUND: Even when older people are discharged directly home after an emergency department (ED) visit, the risk of deterioration of health status and loss of independence persists. We hypothesize that among older adults discharged from the ED, hospital-community transition care provided by geriatric mobile teams (GMTs) may reduce the early readmission rate and level of disability. Such approaches have rarely been evaluated and cannot be generalized yet. Providing evidence of the positive...

Neurotransmitter release occurs through exocytosis of synaptic vesicles. α-Synuclein's function and dysfunction in Parkinson's disease and other synucleinopathies is thought to be tightly linked to synaptic vesicle binding. Age is the biggest risk factor for synucleinopathy, and ~15% of synaptic vesicle proteins have been linked to central nervous system diseases. Yet, age- and disease-induced changes in synaptic vesicles remain unexplored. Via systematic analysis of synaptic vesicles at the...