Aging & Longevity

Cancers invoke various pathways to mitigate external and internal stresses to continue their growth and progression. We previously reported that the eIF2 kinase GCN2 and the integrated stress response are constitutively active in prostate cancer (PCa) and are required to maintain amino acid homeostasis needed to fuel tumor growth. However, although loss of GCN2 function reduces intracellular amino acid availability and PCa growth, there is no appreciable cell death. Here, we discovered that the...

OBJECTIVE: Determine how preventable causes of death contribute to the life expectancy gap between Mexico and Spain.

Genome instability is a hallmark of aging, with the highly repetitive ribosomal DNA (rDNA) within the nucleolus being particularly prone to genome instability. Nucleolar enlargement accompanies aging in organisms ranging from yeast to mammals, and treatment with many antiaging interventions results in small nucleoli. Here, we report that an engineered system to reduce nucleolar size robustly extends budding yeast replicative lifespan in a manner independent of protein synthesis rate or rDNA...

Aging is the greatest risk factor for breast cancer; however, how age-related cellular and molecular events impact cancer initiation is unknown. In this study, we investigated how aging rewires transcriptomic and epigenomic programs of mouse mammary glands at single-cell resolution, yielding a comprehensive resource for aging and cancer biology. Aged epithelial cells exhibit epigenetic and transcriptional changes in metabolic, pro-inflammatory and cancer-associated genes. Aged stromal cells...

The age-associated decline in intestinal stem cell (ISC) function is a key factor in intestinal aging in organisms, resulting in impaired intestinal function and increased susceptibility to age-related diseases. Consequently, it is imperative to develop effective therapeutic strategies to prevent ISC aging and functional decline. In this study, we utilized an aging Drosophila model screening of amino acids and found that asparagine (Asn), a nonessential amino acid in vivo, exhibits its profound...

Sex differences, driven in part by steroid hormones, shape the structure and function of the brain throughout the lifespan and manifest across brain health and disease. The influence of steroid hormones on neuroplasticity, particularly in the adult hippocampus, differs between the sexes, which has important implications for disorders and diseases that compromise hippocampus integrity, such as depression and Alzheimer disease. This Review outlines the intricate relationship between steroid...

CONCLUSION: Most studies supported associations between views of aging and subjective cognition. More longitudinal as well as qualitative research is needed to advance understanding of factors that influence these relationships.

INTRODUCTION: The objective is to investigate the role of digital exclusion in the association between diabetes and cognitive function among adults aged 50 and above.

The complex gut microbiome influences host aging and plays an important role in the manifestation of age-related diseases. Restoring a healthy gut microbiome via Fecal Microbiota Transplantation (FMT) is receiving extensive consideration to therapeutically transfer healthy longevity. Herein, we comprehensively review the benefits of gut microbial rejuvenation - via FMT - to promote healthy aging, with few studies documenting life length properties. This review explores how preconditioning donors...

Alzheimer's Disease (AD) is a complex polygenic neurodegenerative disorder. Its genetic risk's relationship with all-cause dementia may be influenced by the plasma proteome. Up to 40,139 UK Biobank participants aged ≥ 50y at baseline assessment (2006-2010) were followed-up for ≤ 15 y for dementia incidence. Plasma proteomics were performed on a sub-sample of UK Biobank participants (k = 1,463 plasma proteins). AD polygenic risk scores (PRS) were used as the primary exposure and Cox proportional...

Oncogenic transformation and Oct4, Sox2, Klf4 and c-Myc (OSKM)-mediated induction of pluripotency are two independent and incompatible cellular fates. While continuous expression of OSKM can convert normal somatic cells into teratogenic pluripotent cells, it remains speculative what is the impact of transient OSKM expression in cancer cells. Here, we find that OSKM expression limits the growth of transformed lung cells by inducing apoptosis and senescence. We identify Oct4 and Klf4 as the main...

Heterogeneous catalysts with highly dispersed active particles on supports often face stability challenges during high-temperature industrial applications. The ex-solution strategy, which involves in situ extrusion of metals to form socketed particles, shows potential for addressing this stability issue. However, a deeper understanding of the relationship between the socketed geometry of these partially embedded nanoparticles and their catalytic performance is still lacking. Here, in situ...

This cross-sectional study examined the association between gut microbiota composition and locomotive syndrome in 568 healthy Japanese adults (36.8% male, median age 58.5 years) using data from the Kanagawa "ME-BYO" Prospective Cohort Study. Locomotive syndrome was assessed using the 5-question Geriatric Locomotive Function Scale (GLFS-5). Linear discriminant analysis effect size showed an enrichment of Actinobacteria and depletion of Firmicutes in GLFS-5 positive individuals. Classification...

GdVO(4):Eu^(3+) nanoparticles (OVNPs) have previously been shown to exhibit anti-aging effects in old rats.The accelerated aging model (overnutrition in early postnatal ontogenesis (POF)) was used to confirm the effect of OVNPs as a potential geroprotector. A comparative study of the effect of OVNPs, calorierestriction (CR) and CR-mimetic-metformin was carried out using a number of criteria: survival, prooxidant-antioxidant balance in the liver and blood, physiological parameters of male Wistar...

Endothelial cell (EC) senescence is a major contributor in atherosclerosis (AS) development. Herein, the role of forkhead box P transcription factor 1 (FOXP1) and insulin-like growth factor (IGF)-1 in regulating EC senescence during AS progression was investigated. The mRNA and protein expressions were assessed using qRT-PCR and western blot. IL-1β and IL-18 secretion levels were analyzed by ELISA. Cell viability and pyroptosis were determined by MTT assay and flow cytometry, respectively. SA...

This article examines the framing and public perception of longevity biotechnology, or geroscience, which aims to extend both healthspan and lifespan by targeting the biological processes of aging. Although often seen as moving into the mainstream, questions remain about its ability to meet these ambitious goals, given the complexities of understanding and manipulating aging biology. Drawing on an analysis of qualitative studies and surveys conducted over the past two decades, this paper...

There is a critical need to generate age- and sex-specific survival curves to characterize chronological aging consistently across nonhuman primates (NHP) used in biomedical research. Sex-specific Kaplan-Meier survival curves were computed in 12 translational aging models: baboon, bonnet macaque, chimpanzee, common marmoset, coppery titi monkey, cotton-top tamarin, cynomolgus macaque, Japanese macaque, pigtail macaque, rhesus macaque, squirrel monkey, and vervet/African green. After employing...

Non-essential amino acids are often overlooked in biomedical research; however, they are crucial components of organismal metabolism. One such metabolite that is integral to physiological function is serine. Serine acts as a pivotal link connecting glycolysis with one-carbon and lipid metabolism, as well as with pyruvate and glutathione syntheses. Interestingly, increasing evidence suggests that serine metabolism may impact the aging process, and supplementation with serine may confer benefits...

Senescent osteocytes are key contributors to age-related bone loss and fragility; however, the impact of mechanobiological changes in these cells remains poorly understood. This study provides a novel analysis of these changes in primary osteocytes following irradiation-induced senescence. By integrating subcellular mechanical measurements with gene expression analyses, we identified significant, time-dependent alterations in the mechanical properties of senescent bone cells. Increases in...

The intricate neurofluid dynamics and balance is essential in preserving the structural and functional integrity of the brain. Key among these forces are: hemodynamics, such as heartbeat-driven arterial and venous blood flow, and hydrodynamics, such as cerebrospinal fluid (CSF) circulation. The delicate interplay between these dynamics is crucial for maintaining optimal homeostasis within the brain. Currently, the widely accepted framework for understanding brain functions is the Monro-Kellie's...