Aging & Longevity
Insights Into Cockayne Syndrome Type B: What Underlies Its Pathogenesis?
Cockayne Syndrome (CS) is an autosomal recessive disorder arising from mutations in either of two disease-associated genes, ERCC6 or ERCC8. CS patients exhibit cutaneous photosensitivity, neuropathological abnormalities, severe growth retardation, a distinctive facial appearance with pronounced sunken eyes, musculoskeletal anomalies, sensory impairment, and dental decay. Approximately 70% of all CS cases carry ERCC6 mutations; therefore, this review will focus solely on Cockayne Syndrome...
Correction to: Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestradiol, and late-start canagliflozin
No abstract
Rapamycin, Not Metformin, Mirrors Dietary Restriction-Driven Lifespan Extension in Vertebrates: A Meta-Analysis
Dietary restriction (DR) robustly increases lifespan across taxa. However, in humans, long-term DR is difficult to maintain, leading to the search for compounds that regulate metabolism and increase lifespan without reducing caloric intake. The magnitude of lifespan extension from two such compounds, rapamycin and metformin, remains inconclusive, particularly in vertebrates. Here, we conducted a meta-analysis comparing lifespan extension conferred by rapamycin and metformin to DR-mediated...
Reversible proliferative arrest induced by rapid depletion of RNase MRP
Cellular quiescence is a state of reversible proliferative arrest that plays essential roles in development, resistance to stress, aging, and longevity of organisms. Here we report that rapid depletion of RNase MRP, a deeply conserved RNA-based enzyme required for rRNA biosynthesis, induces a long-term yet reversible proliferative arrest in human cells. Severely compromised biogenesis of rRNAs along with acute transcriptional reprogramming precede a gradual decline of the critical cellular...
Epigenetic clocks and DNA methylation biomarkers of brain health and disease
Ageing has profound effects on the human brain across the lifespan. Cognitive testing and brain imaging are currently used to monitor healthy and pathological brain ageing. However, peripheral markers of cognitive function, cognitive ageing and neurological disease could provide a valuable, minimally invasive approach to tracking these processes longitudinally. In this Review, we introduce the concept of DNA methylation-based biomarkers and present current evidence of their potential to address...
Heat shock proteins function as signaling molecules to mediate neuron-glia communication in C. elegans during aging
The nervous system is primarily composed of neurons and glia, and the communication between them has profound roles in regulating the development and function of the brain. Neuron-glia signal transduction is known to be mediated by secreted signals through ligand-receptor interactions on the cell membrane. Here we show a new mechanism for neuron-glia signal transduction, wherein neurons transmit proteins to glia through extracellular vesicles, activating glial signaling pathways. We find that in...
First-generation versus next-generation epigenetic aging clocks: Differences in performance and utility
Aging biomarkers that predict age given methylomic data are referred to as epigenetic aging clocks. While the earliest, first-generation clocks were exclusively trained to predict chronological age, more recent next-generation models have been explicitly trained to associate with health, lifestyle, and/or age-related outcomes. Although these next-generation models have been trained using distinct approaches and techniques, existing evidence indicates that they associate with a greater number of...
Identifying Combinations of Factors Associated With Meeting Age-Specific Sleep Duration Recommendations Among US Midlife and Older Adults: A Study Using Signal Detection Analysis
ObjectiveTo identify subgroups of midlife and older adults from the United States (US), defined by specific combinations of factors, who are more or less likely to meet age-specific sleep duration recommendations.MethodsParticipants (n = 3,124) aged ≥ 40 years were drawn from the 2011-2018 National Health and Nutrition Examination Survey cycles. The primary outcome was meeting age-specific sleep duration recommendations (7 to 9 hours per night) to promote optimal health. Signal detection...
Relationship of Visual Impairment and Poor Mobility With Mortality
CONCLUSIONS: Older adults with both VI and poor mobility are at an additive increased risk of mortality. Future interventions may want to target older adults with both VI and poor mobility to improve survival.
Replication stress responses in human lymphocytes change sex-specifically during aging
The varying incidence of aging-related diseases and the gender gap in life expectancy suggest differences in the aging process between the sexes. Yet, little is known about sex-specific differences in genomic instability, a key factor in aging. Here, we analyzed DNA damage responses (DDRs) in cycling peripheral blood lymphocytes (PBL) and hematopoietic stem and progenitor cells (HSPC) from female and male donors of different age, focusing on replication stress. Transcriptomics revealed striking...
Senescence Cell Induction Methods Display Diverse Metabolic Reprogramming and Reveal an Underpinning Serine/Taurine Reductive Metabolic Phenotype
The relationship between in vitro senescence cell induction and intracellular biomolecular dysregulation is still poorly understood. In this study, we have found that a range of metabolic subphenotypes exists and is dependent on the induction method that is used. To develop understanding of these subphenotypes, we developed and employed a novel bioanalytical pipeline integrating untargeted metabolomics, label-free proteomics, and stable isotope tracing alongside cellular deformability...
Tumor-promoting UBR4 coordinates impaired mitophagy-associated senescence and lung adenocarcinoma pathogenesis
Cellular senescence, an irreversible cell cycle arrest, plays a pivotal role in development, aging, and tumor suppression. However, the fundamental pathway coordinating senescence and neoplastic transformation remains unclear. Here, we describe the tumorigenic involvement of ubiquitin protein ligase E3 component n-recognin 4 (UBR4), an E3 ubiquitin ligase of the N-degron pathway, in lung adenocarcinoma (LUAD). Public genome databases revealed high UBR4 expression in LUAD patients, associated...
ZC3H4 safeguards genome integrity by preventing transcription-replication conflicts at noncoding RNA loci
The cellular networks that maintain genome stability encompass numerous pathways involved in all aspects of nucleic acid metabolism. Through bioinformatic analysis, we identified the Zinc Finger CCCH-Type Containing 4 protein (ZC3H4), a suppressor of noncoding RNA (ncRNA) production, as a pivotal player in this system. Experimentally, ZC3H4 deficiency led to increased DNA damage, abnormal mitosis, and cellular senescence. Biochemical analysis and super-resolution microscopy revealed that the...
FGF21 promotes longevity in diet-induced obesity through metabolic benefits independent of growth suppression
Approximately 35% of US adults over 65 are obese, highlighting the need for therapies targeting age-related metabolic issues. Fibroblast growth factor 21 (FGF21), a hormone mainly produced by the liver, improves metabolism and extends lifespan. To explore its effects without developmental confounders, we generated mice with adipocyte-specific FGF21 overexpression beginning in adulthood. When fed a high-fat diet, these mice lived up to 3.3 years, resisted weight gain, improved insulin...
Ovarian aging at single-cell resolution: Current paradigms and perspectives
Ovarian failure is a key event in female reproductive aging, resulting in the depletion of follicular reserve and a decline in fertility. In addition, it triggers systemic pathological changes, including osteoporosis and cardiovascular disease, due to decreased estrogen levels. Despite extensive study, mapping senescent ovarian cells is challenging due to the multicellular composition and heterogeneity of the ovary. In the past decade, single-cell resolution technologies have provided new...
Skin health and biological aging
Accumulating evidence indicates that biological aging can be accelerated by environmental exposures, collectively called the 'exposome'. The skin, as the largest and most exposed organ, can be viewed as a 'window' for the deep exploration of the exposome and its effects on systemic aging. The complex interplay across hallmarks of aging in the skin and systemic biological aging suggests that physiological processes associated with skin aging influence, and are influenced by, systemic hallmarks of...
Hyponatraemia in ageing
Hyponatraemia is the most common electrolyte disorder in both inpatient and outpatient settings and mostly affects older adults, in whom intrinsic factors (such as chronic heart, liver or kidney diseases and malignancies) and extrinsic factors (such as polypharmacy and malnutrition) favouring hyponatraemia are highly prevalent. Importantly, its occurrence is expected to increase exponentially with global warming. Chronic hyponatraemia is associated with an increased risk of falling, osteoporosis...
Is there a link between gut microbes and ageing?
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How your brain controls ageing - and why zombie cells could be key
No abstract
Associations of physical frailty and polygenic score with incident heart failure in cardiovascular patients: unraveling the mediating role of inflammation
Older adults with established cardiovascular diseases (CVD) are at elevated risk of heart failure (HF). Frailty, a hallmark of multi-system aging, may contribute to HF development through inflammation. However, population-based evidence remains scarce. Leveraging data from 49,530 CVD patients in the UK Biobank, frailty was measured by five components: weight loss, exhaustion, low physical activity, slow walking speed, and low grip strength. We employed Cox regression models to assess the...
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