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Use of the Brief-BESTest partially instrumented with accelerometry to detect balance deterioration in middle-age
CONCLUSIONS: The Brief-BESTest test combined with accelerometry could be a suitable screening tool to identify middle-aged people with early balance deterioration and potentially identify those with poor balance and a possible higher risk for falls. Clinicians and policymakers can use our findings to implement balance assessment programs in patients < 65 years, leading to preventive strategies before the risk increases.
Association between frailty status and risk of chronic lung disease: an analysis based on two national prospective cohorts
CONCLUSION: These findings emphasize the critical role of frailty in the development of CLD, suggesting that targeted interventions could reduce CLD risk.
Centenarians of the Basque Country are resilient to cancer
Cancer is one of the leading causes of death and its prevalence increases with age. While centenarians exhibit extreme longevity and potential to avoid or delay aging-related diseases, their response to cancer is still barely explored. Our study took advantage of the Electronic Health Records to retrospectively compare the severity of cancer in centenarians (n = 649) and non-centenarians (n = 62,753) in the Basque Country (province of Gipuzkoa), Spain, through analyzing all the recorded...
Mapping the gut microbial structural variations in healthy aging within the Chinese population
Mapping gut microbial structural variants (SVs) during human aging may provide fundamental knowledge and mechanistic understanding of the gut microbiome's relationship with healthy aging. We characterize gut microbial SVs from 3,230 Chinese participants, identifying key SVs associated with aging, healthy aging, and age-related chronic diseases. Our findings reveal a pattern of copy number loss in aging-related SVs, with 35 core SVs consistently detected. Additionally, eight SVs distinguish...
Successful Aging Rates of Global Older Adults: A Systematic Review and Meta-analysis
CONCLUSIONS AND IMPLICATIONS: The overall estimated SA rate among people aged ≥60 years was 22% globally. The SA criteria mainly include 6 aspects: good psychological status, no major diseases, high cognitive function, high physical function, active social engagement, and no disability. Emphasizing the importance of psychological well-being and chronic disease management, the findings offer valuable insights for future research and policy making related to the welfare of aging populations.
Aurora B inhibitors promote RB hypophosphorylation and senescence independent of p53-dependent CDK2/4 inhibition
Aurora B kinase (AURKB) inhibitors have been trialled in a range of different tumour types but are not approved for any indication. Expression of the human papilloma virus (HPV) oncogenes and loss of retinoblastoma (RB) protein function has been reported to increase sensitivity to AURKB inhibitors but the mechanism of their contribution to sensitivity is poorly understood. Two commonly reported outcomes of AURKB inhibition are polyploidy and senescence, although their relationship is unclear....
Top Alzheimer’s researcher goes ‘on leave’ amid misconduct concerns
Berislav Zlokovic no longer heads neuroscience institute, University of Southern California email reveals
Efficient PHB2 (prohibitin 2) exposure during mitophagy depends on VDAC1 (voltage dependent anion channel 1)
Exposure of inner mitochondrial membrane resident protein PHB2 (prohibitin 2) during autophagic removal of depolarized mitochondria (mitophagy) depends on the ubiquitin-proteasome system. This uncovering facilitates the PHB2 interaction with phagophore membrane-associated protein MAP1LC3/LC3. It is unclear whether PHB2 is exposed randomly at mitochondrial rupture sites. Prior knowledge and initial screening indicated that VDAC1 (voltage dependent anion channel 1) might play a role in this...
Macrophage LRRK2 hyperactivity impairs autophagy and induces Paneth cell dysfunction
LRRK2 polymorphisms (G2019S/N2081D) that increase susceptibility to Parkinson's disease and Crohn's disease (CD) lead to LRRK2 kinase hyperactivity and suppress autophagy. This connection suggests that LRRK2 kinase inhibition, a therapeutic strategy being explored for Parkinson's disease, may also benefit patients with CD. Paneth cell homeostasis is tightly regulated by autophagy, and their dysfunction is a precursor to gut inflammation in CD. Here, we found that patients with CD and mice...
Redox regulation, protein S-nitrosylation, and synapse loss in Alzheimer's and related dementias
Redox-mediated posttranslational modification, as exemplified by protein S-nitrosylation, modulates protein activity and function in both health and disease. Here, we review recent findings that show how normal aging, infection/inflammation, trauma, environmental toxins, and diseases associated with protein aggregation can each trigger excessive nitrosative stress, resulting in aberrant protein S-nitrosylation and hence dysfunctional protein networks. These redox reactions contribute to the...
Iron homeostasis and neurodegeneration in the ageing brain: Insight into ferroptosis pathways
Ageing is a major risk factor for various chronic diseases and offers a potential target for developing novel and broadly effective preventatives or therapeutics for age-related conditions, including those affecting the brain. Mechanisms contributing to ageing have been summarized as the hallmarks of ageing, with iron imbalance being one of the major factors. Ferroptosis, an iron-mediated lipid peroxidation-induced programmed cell death, has recently been implicated in neurodegenerative diseases...
VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction
Alzheimer's disease (AD) patients exhibit neuropsychiatric symptoms that extend beyond classical cognitive deficits, suggesting involvement of subcortical areas. Here, we investigated the role of midbrain dopamine (DA) neurons in AD using the amyloid + tau-driven 3xTg-AD mouse model. We found deficits in reward-based operant learning in AD mice, suggesting possible VTA DA neuron dysregulation. Physiological assessment revealed hyperexcitability and disrupted firing in DA neurons caused by...
Should Alzheimer's be diagnosed with a blood test? Proposal sparks controversy
No abstract
The role of inflammation induced by necroptosis in the development of fibrosis and liver cancer in novel knockin mouse models fed a western diet
Non-resolving, chronic inflammation (inflammaging) is believed to play an important role in aging and age-related diseases. The goal of this study was to determine if inflammation induced by necroptosis arising from the liver plays a role in chronic liver disease (CLD) and liver cancer in mice fed a western diet (WD). Necroptosis was induced in liver using two knockin (KI) mouse models that overexpress genes involved in necroptosis (Ripk3 or Mlkl) specifically in liver (i.e., hRipk3-KI and...
The influence of a human macronutrient-matched diet on phenotypes in old mice
Preclinical rodent models are essential research tools for improving understanding of physiological aging processes in humans. However, the translatability of findings obtained leveraging rodent models to humans is limited, likely due in part to differences in macronutrient composition of the diets. Here, we investigated the impact of a 3-month diet intervention in old male C57BL/6JN mice in which the macronutrient composition was aligned with that of a midlife/older adult in the United States,...
Human-induced pluripotent stem cell-derived microglia integrate into mouse retina and recapitulate features of endogenous microglia
Microglia exhibit both maladaptive and adaptive roles in the pathogenesis of neurodegenerative diseases and have emerged as a cellular target for central nervous system (CNS) disorders, including those affecting the retina. Replacing maladaptive microglia, such as those impacted by aging or over-activation, with exogenous microglia that can enable adaptive functions has been proposed as a potential therapeutic strategy for neurodegenerative diseases. To investigate microglia replacement as an...
Contemporary small-scale subsistence populations offer unique insights into human musculoskeletal health and aging
Human foragers avoid noncommunicable diseases that are leading causes of mortality, partly because physically active lifestyles promote healthy aging. High activity levels also promote tissue damage accumulation from wear-and-tear, increase risk of injury and disability which compromise productivity, and reduce energetic investments in somatic maintenance given constrained energy expenditure. Constraints intensify when nutrient supply is limited and surplus energy is directed toward pathogen...
Progressive decline in old pole gene expression signal enhances phenotypic heterogeneity in bacteria
Cell growth and gene expression are heterogeneous processes at the single-cell level, leading to the emergence of multiple physiological states within bacterial populations. Aging is a known deterministic driver of growth asymmetry; however, its role in gene expression heterogeneity remains elusive. Here, we show that aging mother cells undergo a progressive decline in old pole activity, generating asymmetry in protein partitioning, gene expression, and cell morphology. We demonstrate that...
Redox regulation, protein S-nitrosylation, and synapse loss in Alzheimer's and related dementias
Redox-mediated posttranslational modification, as exemplified by protein S-nitrosylation, modulates protein activity and function in both health and disease. Here, we review recent findings that show how normal aging, infection/inflammation, trauma, environmental toxins, and diseases associated with protein aggregation can each trigger excessive nitrosative stress, resulting in aberrant protein S-nitrosylation and hence dysfunctional protein networks. These redox reactions contribute to the...
Iron homeostasis and neurodegeneration in the ageing brain: Insight into ferroptosis pathways
Ageing is a major risk factor for various chronic diseases and offers a potential target for developing novel and broadly effective preventatives or therapeutics for age-related conditions, including those affecting the brain. Mechanisms contributing to ageing have been summarized as the hallmarks of ageing, with iron imbalance being one of the major factors. Ferroptosis, an iron-mediated lipid peroxidation-induced programmed cell death, has recently been implicated in neurodegenerative diseases...