Aging & Longevity
Profiling Epigenetic Aging at Cell-Type Resolution Through Long-Read Sequencing
DNA methylation can give rise to robust biomarkers of aging, yet most studies profile it at the bulk tissue level, which masks cell type-specific alterations that may follow distinct aging trajectories. Long-read sequencing technology enables methylation profiling of extended DNA fragments, enabling mapping to their cell type of origin. In this study, we introduce a framework for evaluating cell type-specific aging using long-read sequencing data, without the need for cell sorting. Leveraging...
Bridging expectations and science: a roadmap for the future of longevity interventions
The field of longevity interventions has witnessed rapid expansion, driven by scientific advancements alongside growing industry and consumer interest. However, no longevity intervention has yet been proven effective or ready for widespread clinical adoption. A substantial gap persists between public expectations and the current scientific realities. This article explores four key themes: (1) consumer priorities regarding longevity interventions, (2) the type and depth of scientific information...
The combination of hawthorn extract administration and high-intensity interval training (HIIT) alleviates hippocampus damage in aged rats: the behavioral, molecular and histological evaluations
The aging process results in a gradual decline in brain function, characterized by heightened hippocampal atrophy and dysfunction. Physical activity can enhance cognitive skills in elderly individuals and is significant in the prevention of neurodegenerative illnesses. Hawthorn (Crataegus oxyacantha) is a fruit-bearing shrub with a longstanding history as a medicinal agent. Currently, hawthorn is predominantly utilized for a range of pathological diseases. This research is designed to assess the...
Identification of Functional Cellular Markers Related to Human Health, Frailty and Chronological Age
Aging leads to a decline in physiological reserves, an increase in age-related diseases, reduced functional ability and a shortened healthspan. While molecular markers of chronological aging exist, their link to general health and intrinsic capacity (IC), a composite measure of physical and mental capacities, remains unclear. This study integrates the WHO's Healthy Aging framework with geroscience to explore fibroblasts as indicators of health. We assessed primary skin fibroblasts from 133...
Satellite glial cells: Shaping peripheral input into the brain-body axis?
Satellite glial cells (SGCs) are peripheral nervous system glial cells enveloping sensory and sympathetic ganglion neuronal soma. Traditionally viewed as mere supportive cells, recent studies reveal SGCs' dynamic role in regulating sensory and autonomic processing, positioning them to shape peripheral neural signaling. This role has the potential to impact the healthy function of numerous biological processes and contribute to disease progression. Studies now implicate peripheral sensory and...
More TOR: The expanding role of mTOR in regulating immune responses
The mammalian/mechanistic target of rapamycin (mTOR) is an evolutionarily conserved multi-node signaling pathway that integrates critical environmental cues to control cellular growth. Decades worth of studies have intricately dissected the mTOR pathway to identify regulatory signals that are essential for regulating immune cell activation, differentiation, and function. As the mTOR field continues to evolve, so too does our understanding of these new findings in immune cells. Our group and...
Leaf economic strategies drive global variation in phosphorus stimulation of terrestrial plant production
Plant biomass and its allocation are fundamental for understanding biospheric matter production. However, the impacts of atmospheric phosphorus (P) deposition on species-specific biomass and its allocation in global terrestrial plants remain unclear. By synthesizing 5548 observations of plant biomass and its allocation related to P addition worldwide, we find that P addition increases plant biomass by an average of 35% globally. This increase varies across plant functional groups, with stronger...
From hormones to neurodegeneration: how FSH drives Alzheimer's disease
The role and function of follicle-stimulating hormone in the gonads have been extremely studied. However, recent research has begun to explore the relationship between elevated follicle-stimulating hormone levels and the prevalence of extragonadal disorders, particularly in perimenopausal and postmenopausal women. These disorders include endometrial cancer, osteoporosis, obesity, and atherosclerosis. This review provides new insights into the relationship between follicle-stimulating hormone and...
CITA GO-ON study. A community based multidomain lifestyle intervention to prevent cognitive decline. Protocol design and recruitment process
INTRODUCTION: Growing research suggests that dementia is a complex disorder with multiple risk factors and causes. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) demonstrated that lifestyle interventions could confer cognitive benefits. Inspired by this, the GOIZ-ZAINDU (GZ) feasibility study adapted the FINGER approach to the Basque context. Building upon the GZ study, the CITA GO-ON trial aims to enhance and expand the evidence supporting...
Metabolomic Profiling Identifies Early Biomarkers of Frailty, Balance Impairment, and Fall Risks in Older Adults
CONCLUSION: Metabolomics offers a promising approach to identify early biomarkers of frailty, balance impairment, and fall risks in older adults. The integration of metabolic profiles with clinical assessments could lead to more precise and personalized healthcare interventions, improving fall prevention strategies and frailty management. Future studies with larger cohorts are needed to validate these findings and explore the clinical utility of Metabolomics in aging-related healthcare.
Targeting autophagy in doxorubicin-induced cardiotoxicity: A comprehensive review of scientific landscapes and therapeutic innovations
Doxorubicin (DOX)-induced cardiotoxicity (DIC) poses a major threat to elderly cancer patients, often leading to severe cardiac dysfunction and complicating the outcome of cancer treatment. Autophagy is one of the core mechanisms of DIC and is considered a key therapeutic target. We analyzed the status of research in the field of autophagy in DIC via bibliometric methods. A total of 292 publications related to this topic were identified and included. Furthermore, based on included publications...
Ageing is linked to inflammation - but only in the industrialized world
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Sex-specific associations between homelessness and cerebrovascular disease among aging US veterans in the Veterans Affairs healthcare system
Homelessness and chronic disease have been previously linked. We examined the bidirectional, sex-specific, relationship between homelessness and cerebrovascular disease among aging veterans seeking U.S. Department of Veterans Affairs (VA) healthcare services. A retrospective study was conducted among a cohort of 4,061,031 veterans (mean [± standard deviation] age: 68.7 [± 10.3] years; 94.6% men) followed between 2017 and 2021 and defined through linkage of VA Corporate Data Warehouse, Homeless...
Synbiotic supplementation enhances memory processes in adult and aged male rats
Synbiotic formulations, which combine prebiotics and probiotics in their composition, have shown promise in improving brain function and cognitive performance. However, the mechanisms by which synbiotics exert their beneficial effects on memory processes, particularly in the context of aging, remain unclear. In the present study, we investigated the effects of synbiotics supplementation on memory updating (reversal learning) and extinction in adult and aged rats. We also assessed the impact of...
Nonuniversality of inflammaging across human populations
Inflammaging, an age-associated increase in chronic inflammation, is considered a hallmark of aging. However, there is no consensus approach to measuring inflammaging based on circulating cytokines. Here we assessed whether an inflammaging axis detected in the Italian InCHIANTI dataset comprising 19 cytokines could be generalized to a different industrialized population (Singapore Longitudinal Aging Study) or to two indigenous, nonindustrialized populations: the Tsimane from the Bolivian Amazon...
Epigenetic erosion of H4K20me1 induced by inflammation drives aged stem cell ferroptosis
Aging is characterized by a decline in the functionality and number of stem cells across the organism. In this study, we uncovered a mechanism by which systemic inflammation drives muscle stem cell (MuSC) aging through epigenetic erosion. We demonstrate that age-related inflammation decreases monomethylation of H4K20 in MuSCs, disrupting their quiescence and inducing ferroptosis, a form of iron-dependent cell death. Our findings show that inflammatory signals downregulate Kmt5a, the enzyme...
A TFEB-TGFbeta axis systemically regulates diapause, stem cell resilience and protects against a senescence-like state
Diapause is a long-lived state of resilience that allows organisms to outlast adversity. Caenorhabditis elegans can endure months in a fasting-induced adult reproductive diapause (ARD) and, upon refeeding, regenerate and reproduce. Here we find that mutants of ARD master regulator hlh-30/TFEB arrest in a senescence-like state during ARD and refeeding, in which germline stem cells are characterized by DNA damage, nucleolar expansion, cell cycle arrest and mitochondrial dysfunction, alongside...
Clusterin drives myeloid bias in aged hematopoietic stem cells by regulating mitochondrial function
Aged hematopoietic stem cells (HSCs) exhibit diminished self-renewal and myeloid-biased differentiation with a decline in hematopoiesis and adaptive immune function. However, the molecular regulation of this impaired function remains largely unknown. Here, through an in vivo CRISPR-Cas9-based screen, we uncovered clusterin (Clu) as a driver of biased differentiation. Clu is upregulated in aged HSCs, and its knockout diminishes biased differentiation. Clu promotes mitochondrial hyperfusion by...
Altered Relaxation and Mitochondria-Endoplasmic Reticulum Contacts Precede Major (Mal)Adaptations in Aging Skeletal Muscle and Are Prevented by Exercise
Sarcopenia, or age-related muscle dysfunction, contributes to morbidity and mortality. Besides decreases in muscle force, sarcopenia is associated with atrophy and fast-to-slow fiber type switching, which is typically secondary to denervation in humans and rodents. However, very little is known about cellular changes preceding these important (mal)adaptations. To this matter, mitochondria and the sarcoplasmic reticulum are critical for tension generation in myofibers. They physically interact at...
Translational potential of GADD45alpha: biomarker and therapeutic target in age-associated neurodegeneration and longevity
Aging features a gradual decline in genomic integrity, epigenetic fidelity, and cellular homeostasis, driving the onset of chronic pathologies such as cancer, neurodegeneration, and metabolic disease. Growth arrest and DNA damage-inducible 45 alpha (GADD45α) functions as a pivotal stress-response mediator, coordinating DNA repair, cell-cycle arrest, oxidative stress defence, mitochondrial quality control, and chromatin remodeling. Researchers have extensively studied GADD45α in tumor...
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