Aging & Longevity
Amyloid-beta peptide toxicity in the aged brain is a one-way journey into Alzheimer's disease
Aging is the primary risk factor for Alzheimer's disease (AD), and the aging brain shares many characteristics with the early stages of AD. This study investigates the interplay between aging and amyloid-beta (Aβ) induced pathology. We developed an AD-like in vivo model, using the stereotactic injection of Aβ(1-42) oligomers into the hippocampi of aged mice. Cognitive impairments were assessed using a Y maze. Immunohistochemical and protein analyses were conducted to evaluate neuronal survival,...
The Redox Activity of Protein Disulphide Isomerase Functions in Non-Homologous End-Joining Repair to Prevent DNA Damage
DNA damage is a serious threat to cellular viability, and it is implicated as the major cause of normal ageing. Hence, targeting DNA damage therapeutically may counteract age-related cellular dysfunction and disease, such as neurodegenerative conditions and cancer. Identifying novel DNA repair mechanisms therefore reveals new therapeutic interventions for multiple human diseases. In neurons, non-homologous end-joining (NHEJ) is the only mechanism available to repair double-stranded DNA breaks...
Bidirectional association between physical activity and sleep in healthy Japanese super-seniors: the Japan Healthy Aging Study (J-HAS)
To address the challenges of an ageing population, it is important to promote health by identifying factors for healthy ageing. The aim of this study was to investigate the bidirectional association between physical activity (PA) and sleep in healthy Japanese super-seniors over the age of 80. For approximately 1 year, 124 participants wore wearable devices and answered daily lifestyle questionnaires. PA was defined as daily step count and minutes in light activity. Sleep was measured using 24-h...
Age-related decline in IgM responses associate with reduced opsonophagocytic activity following PCV13 vaccination
Pneumococcal vaccination is crucial in preventing Streptococcus pneumoniae infections in older adults. However, vaccine responses often diminish with age. This study investigates serotype-specific IgM and IgG responses in relation to opsonophagocytic activity (OPA) following thirteen-valent pneumococcal conjugate (PCV13) vaccination in younger (26-49 y; n = 44), middle-aged (50-64 y; n = 71), and older adults (65-98 y; n = 141). Both OPA and IgM responses declined with age, while IgG responses...
Cartilage degradation is followed by PAC1 receptor reduction in articular cartilage of human knee joints
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide expressed in the nervous system and also in various peripheral tissues, including the musculoskeletal system. PACAP has an important function in the regulation of chondrogenesis and plays a protective role in cartilage oxidative and mechanical stress. PACAP knockout (KO) mice show early signs of aging and osteoarthritis in knee joint articular cartilage. Its specific, most potent receptor is the PAC1 receptor, the...
Small-molecule dissolution of stress granules by redox modulation benefits ALS models
Neurodegenerative diseases, such as amyotrophic lateral sclerosis, are often associated with mutations in stress granule proteins. Aberrant stress granule condensate formation is associated with disease, making it a potential target for pharmacological intervention. Here, we identified lipoamide, a small molecule that specifically prevents cytoplasmic condensation of stress granule proteins. Thermal proteome profiling showed that lipoamide stabilizes intrinsically disordered domain-containing...
Aging and injury drive neuronal senescence in the dorsal root ganglia
Aging negatively impacts central nervous system function; however, there is limited information about the cellular impact of aging on peripheral nervous system function. Importantly, injury to vulnerable peripheral axons of dorsal root ganglion (DRG) neurons results in somatosensory dysfunction, such as pain, at higher rates in aged individuals. Cellular senescence is common to both aging and injury and contributes to the aged pro-inflammatory environment. We discovered DRG neuron senescence in...
Impact of multidimensional assessment on anti-fracture treatment decisions in patients with fragility hip fractures within a Fracture Liaison Service
CONCLUSION: The integration of the MPI into multidisciplinary taking care of old patients with hip fractures may provide a structured approach for individualizing treatment decisions, considering aspects such as prognosis, functional autonomy, and cognitive status. Further studies are needed to validate the long-term outcomes of this approach.
Crustal to mantle melt storage during the evolution of Hawaiian volcanoes
As the Pacific Plate migrates over the mantle plume below Hawai'i, magma flux decreases, resulting in changes in eruptive volume, style, and composition. It is thought that melt storage becomes deeper and ephemeral with the transition from highly voluminous tholeiitic (shield stage) to the less voluminous alkaline (post-shield and rejuvenation stages) magmatism. To quantitatively test this, we applied high-precision fluid inclusion barometry via Raman spectroscopy to samples from representative...
Loss of Subsidized Drug Coverage and Mortality among Medicare Beneficiaries
CONCLUSIONS: Loss of drug subsidies after Medicaid disenrollment was associated with higher mortality among low-income Medicare beneficiaries. (Funded by the National Institute on Aging and others.).
Correction to 'Broad repression of DNA repair genes in senescent cells identified by integration of transcriptomic data'
No abstract
Thymic Bmi-1 hampers gammadeltaT17 generation and its derived RORgammat-IL-17A signaling to delay cardiac aging
New immunosenescence targets for preventing senescence-associated pathological cardiac hypertrophy (SA-PCH) need to be explored. In the present study, with physiologically aged human and mouse samples, the IL-17A level increased with physiological aging, heart failure (HF), and SA-PCH and was negatively correlated with thymic Bmi-1 expression. Bmi-1^(f/f)LckCre^(+) mice and Bmi-1^(f/f) littermates were generated to determine whether Bmi-1 delayed T cell aging by maintaining thymic T cell...
Identifying New Risk Factors for Comorbidities in the Elderly
CONCLUSION: This study underscores the importance of HDL-C and FBG as critical biomarkers for assessing comorbidity risk in the elderly and reveals the potential application of the nomogram prediction model in the risk prediction and management of elderly comorbidities. These findings support using these indicators in predicting and intervening comorbidities in the elderly, providing substantial evidence for further research and clinical practice.
The Impact of Living at Moderate Altitude in the United States: Epidemiology and Key Research Questions
Over the last twenty years, the United States (US) has seen a significant population migration into moderate elevation locations (defined as elevations 1,800- 2,500 meters (m) for the purposes of this review). While considerable research has investigated how chronic diseases are impacted on acute ascent to high altitude, little research has examined how residing at high altitude impacts longer term health including risk of various disease states and long-term morbidity, with even fewer studies...
A 20-Second Video-Based Assessment of Cognitive Frailty: Results from a Cohort Study within the Precision Aging Network
CONCLUSIONS: The 20-second vFM test offers a practical, non-invasive, easy-to-implement, and accessible solution for objectively evaluating cognitive frailty, demonstrating high predictive accuracy in distinguishing at-risk individuals. Its integration into telehealth platforms could enhance early detection and enable timely interventions, promoting healthier aging trajectories. Further longitudinal studies are recommended to validate its utility in tracking cognitive and physical decline over...
Decoding Precision Aging: The Intersection of Cognitive Decline, Frailty, and Hormonal Biomarkers
CONCLUSIONS: This study highlights practical and efficient methods for assessing frailty emphasizing the value of dual-task testing and cortisol measures in identifying individuals at higher risk for cognitive and physical decline. The findings underscore the importance of integrating hormonal markers with cognitive and physical assessments to enhance risk stratification and intervention planning in aging populations.
Reference centiles for intrinsic capacity to monitor clinical health outcomes in real-world primary care cohorts
Intrinsic capacity (IC) refers to physical and mental capacities that determine healthy aging. IC is the central element of the World Health Organization care pathway 'Integrated Care for Older People' (ICOPE). However, the operationalization of a composite IC measurement in clinical settings remains to be defined. We used screening data from ICOPE implementation in a real-life population of 27,706 adults 60 years or older that were users of primary care services to elaborate and cross-validate...
CaMK modulates sensory neural activity to control longevity and proteostasis
The impact of neural activity on aging and longevity remains poorly understood, with limited understanding of the specific neuron groups and molecular mechanisms that regulate lifespan. In this study, we uncover a correlation between human longevity and reduced CaMK4 expression in the frontal cortex. We further show that this link is conserved in Caenorhabditis elegans, where the loss of the homolog CMK-1 leads to increased longevity and enhanced proteostasis. These beneficial effects are...
DLK/JNK3 Upregulation Aggravates Hair Cell Senescence in Mice Cochleae via Excessive Autophagy
Cell death mediated by the abnormal activation of autophagy has been observed in many neurodegenerative diseases. Dual leucine zipper kinase (DLK), a member of the mitogen-activated protein kinase cascade, plays a key role in regulating cellular autophagy and the progression of neurodegenerative diseases. However, its role in age-related hearing loss has not been reported. In this study, we found that DLK, phosphorylated c-Jun N-terminal kinase (p-JNK), and JNK3 expression increased in the...
Detecting the fractal physical activity pattern in aged adults with cerebral small vessel disease
CONCLUSION: These findings demonstrate the presence of obvious fractal physical activity complexity in aged adults with cSVD.
Aging and Longevity: Latest results from PubMed
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