Aging & Longevity

No abstract

The extracellular matrix is an essential component and constitutes a dynamic microenvironment of the vessel wall with an indispensable role in vascular homeostasis and disease. From early development through to ageing, the vascular extracellular matrix undergoes various biochemical and biomechanical alterations in response to diverse environmental cues and exerts precise regulatory control over vessel remodelling. Advances in novel technologies that enable the comprehensive evaluation of...

Hepatocellular carcinoma (HCC) originates from differentiated hepatocytes undergoing compensatory proliferation in livers damaged by viruses or metabolic-dysfunction-associated steatohepatitis (MASH)¹. While increasing HCC risk², MASH triggers p53-dependent hepatocyte senescence³, which we found to parallel hypernutrition-induced DNA breaks. How this tumour-suppressive response is bypassed to license oncogenic mutagenesis and enable HCC evolution was previously unclear. Here we identified the...

Biological ageing can be defined as a gradual loss of homeostasis across various aspects of molecular and cellular function^(1,2). Mammalian brains consist of thousands of cell types³, which may be differentially susceptible or resilient to ageing. Here we present a comprehensive single-cell RNA sequencing dataset containing roughly 1.2 million high-quality single-cell transcriptomes of brain cells from young adult and aged mice of both sexes, from regions spanning the forebrain, midbrain and...

The forces generated by action potentials in muscle cells shuttle blood, food and waste products throughout the luminal structures of the body. Although non-invasive electrophysiological techniques exist^(1-3), most mechanosensors cannot access luminal structures non-invasively^(4-6). Here we introduce non-toxic ingestible mechanosensors to enable the quantitative study of luminal forces and apply them to study feeding in living Caenorhabditis elegans roundworms. These optical 'microgauges'...

Aging is a process accompanied by functional decline in tissues and organs with great social and medical consequences. Developing effective anti-aging strategies is of great significance. In this study, we demonstrated that transplantation of young hematopoietic stem cells (HSCs) into old mice can mitigate aging phenotypes, underscoring the crucial role of HSCs in the aging process. Through comprehensive molecular and functional analyses, we identified a subset of HSCs in aged mice that exhibit...

Although cellular senescence has been recognized as a hallmark of aging, it is challenging to detect senescence cells (SnCs) due to their high level of heterogeneity at the molecular level. Machine learning (ML) is likely an ideal approach to address this challenge because of its ability to recognize complex patterns that cannot be characterized by one or a few features, from high-dimensional data. To test this, we evaluated the performance of four ML algorithms including support vector machines...

CONCLUSIONS: Our study identified a potential association between frailty and respiratory symptoms. Inflammation and ageing may be essential factors mediating this association.

The proportion of older individuals needing liver transplantation is growing, resulting in an increasingly frail patient population. Frailty constitutes a constellation of cognitive and physical symptoms associated with aging and increases the risk of morbidity and mortality. Senescence is a programmed cell fate in response to stress implicated in causing frailty, age-related diseases, and aging itself. This study explores the relationship between cellular senescence, physical frailty, and liver...

Cancer and aging are inextricably linked, and older adults are a significant proportion of those diagnosed, treated, and living with and beyond a cancer diagnosis. Several large prospective studies have enhanced our understanding of how to improve the assessment, treatment, and outcomes of older adults with cancer starting therapy. This article summarizes three recent high-impact trials that produced practice-changing implications for the management of older adults with cancer that led to...

CONCLUSIONS: These findings demonstrate a variety of barriers across stakeholder types and provide valuable insights for developing strategies to effectively promote older adult participation in fall prevention activities to reduce falls and enhance healthy aging.

Age-dependent sensory impairment, memory loss, and cognitive decline are generally attributed to neuron loss, synaptic dysfunction, and decreased neuronal activities over time. Concurrently, increased neuronal activity is reported in humans and other organisms during aging. However, it is unclear whether neuronal hyperactivity is the cause of cognitive impairment or a compensatory mechanism of circuit dysfunction. The roundworm Caenorhabditis elegans exhibits age-dependent declines in an...

Spns1 mediates the rate-limiting efflux of lysophospholipids from the lysosome to the cytosol. Deficiency of Spns1 is associated with embryonic senescence, as well as liver and skeletal muscle atrophy in animal models. However, the mechanisms by which Spns1 transports lysophospholipid and proton sensing remain unclear. Here, we present a cryogenic electron microscopy structure of human Spns1 in lysophosphatidylcholine (LPC)-bound lumen-facing conformation. Notably, LPC snugly binds within the...

A wave of studies has recently emphasized the influence of sex chromosomes on both lifespan and actuarial senescence patterns across vertebrates and invertebrates. Basically, the heterogametic sex (XY males in XX/XY systems or ZW females in ZW/ZZ systems) typically displays a lower lifespan and a steeper rate of actuarial senescence than the homogametic sex. However, whether these effects extend to the senescence patterns of other phenotypic traits or physiological functions is yet to be...

Cellular senescence plays a significant role in tissue aging. Senescent cells, which resist apoptosis while remaining metabolically active, generate endogenous DNA-damaging agents, primarily reactive oxygen species. Efficient DNA repair is therefore crucial in these cells, especially when they undergo senescence escape, resuming DNA replication and cellular proliferation. To investigate whether senescent cell transcriptomes reflect adequate DNA repair capacity, we conducted a comprehensive...

Structural brain changes underlie cognitive changes and interindividual variability in cognition in older age. By using structural MRI data-driven clustering, we aimed to identify subgroups of cognitively unimpaired older adults based on brain change patterns and assess how changes in cortical thickness, surface area, and subcortical volume relate to cognitive change. We tested (1) which brain structural changes predict cognitive change (2) whether these are associated with core cerebrospinal...

Optical approaches to monitor neural activity are transforming neuroscience, owing to a fast-evolving palette of genetically encoded molecular reporters. However, the field still requires robust and label-free technologies to monitor the multifaceted biomolecular changes accompanying brain development, aging or disease. Here, we have developed vibrational fiber photometry as a low-invasive method for label-free monitoring of the biomolecular content of arbitrarily deep regions of the mouse brain...

CONCLUSION: This study provides insight into the short-term aftereffects of transcranial current stimulation in the aging and AD brain and is the first animal study to compare brain activity between tACS and tDCS treatments.

Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to protein deficiency are well-studied, there is a significant gap in our understanding of how organisms adaptively suppress excessive protein intake. In the present study, utilizing the fruit fly, Drosophila melanogaster, we discover that the peptide hormone CCHamide1 (CCHa1), secreted by enteroendocrine cells in response to a...

The mechanisms underlying the impact of probiotic supplementation on health remain largely elusive. While previous studies primarily focus on the discovery of novel bioactive bacteria and alterations in the microbiome environment to explain potential probiotic effects, our research delves into the role of living Lactiplantibacillus (formerly known as Lactobacillus) and their conditioned media, highlighting that only the former, not dead bacteria, enhance the healthspan of Caenorhabditis elegans...