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Aβ-driven nuclear pore complex dysfunction alters activation of necroptosis proteins in a mouse model of Alzheimer's disease
The emergence of Aβ pathology is one of the hallmarks of Alzheimer's disease (AD), but the mechanisms and impact of Aβ in progression of the disease is unclear. The nuclear pore complex (NPC) is a multi-protein assembly in mammalian cells that regulates movement of macromolecules across the nuclear envelope; its function is shown to undergo age-dependent decline during normal aging and is also impaired in multiple neurodegenerative disorders. Yet not much is known about the impact of Aβ on NPC...
BRD4/MAP2K7/PGF Signaling Axis Promotes Senescence and Extracellular Matrix Metabolism of Nucleus Pulposus Cells in Intervertebral Disk Degeneration
Intervertebral disk degeneration (IDD) is a common age-related degenerative disease of the spine that imposes a substantial economic burden on both families and society. Despite substantial advances in understanding the mechanisms underlying IDD, effective therapeutic interventions for its treatment and prevention remain elusive. Our previous study identified a positive correlation between IDD severity and bromodomain-containing protein 4 (BRD4) expression. However, the multifaceted role of BRD4...
Knowing the enemy: strategic targeting of complement to treat Alzheimer disease
The complement system protects against infection, positively responds to tissue damage, clears cell debris, directs and modulates the adaptive immune system, and functions in neuronal development, normal synapse elimination and intracellular metabolism. However, complement also has a role in aberrant synaptic pruning and neuroinflammation - processes that lead to a feedforward loop of inflammation, injury and neuronal death that can contribute to neurodegenerative and neurological disorders,...
High-content screening identifies ganoderic acid A as a senotherapeutic to prevent cellular senescence and extend healthspan in preclinical models
Accumulated senescent cells during the aging process are a key driver of functional decline and age-related disorders. Here, we identify ganoderic acid A (GAA) as a potent anti-senescent compound with low toxicity and favorable drug properties through high-content screening. GAA, a major natural component of Ganoderma lucidum, possesses broad-spectrum geroprotective activity across various species. In C. elegans, GAA treatment extends lifespan and healthspan as effectively as rapamycin....
A fungal pathogen suppresses host leaf senescence to increase infection
Phytopathogens such as Puccinia striiformis f. sp. tritici (Pst) induce pigment retention at pathogen infection sites. Although pigment retention is commonly observed in diverse pathosystems, its underlying physiological mechanism remains largely unclear. Herein, we identify and characterize a wheat leaf senescence gene, TaSGR1, which enhances resistance against Pst by promoting leaf senescence and H(2)O(2) accumulation while inhibiting photosynthesis. Knockout of TaSGR1 (STAYGREEN) in wheat...
Single-cell parallel analysis of DNA damage and transcriptome reveals selective genome vulnerability
Maintenance of genome integrity is paramount to molecular programs in multicellular organisms. Throughout the lifespan, various endogenous and environmental factors pose persistent threats to the genome, which can result in DNA damage. Understanding the functional consequences of DNA damage requires investigating their preferred genomic distributions and influences on gene regulatory programs. However, such analysis is hindered by both the complex cell-type compositions within organs and the...
Optimal dietary patterns for healthy aging
As the global population ages, it is critical to identify diets that, beyond preventing noncommunicable diseases, optimally promote healthy aging. Here, using longitudinal questionnaire data from the Nurses' Health Study (1986-2016) and the Health Professionals Follow-Up Study (1986-2016), we examined the association of long-term adherence to eight dietary patterns and ultraprocessed food consumption with healthy aging, as assessed according to measures of cognitive, physical and mental health,...
Harnessing lysohormesis for healthy ageing
No abstract
Global, regional, and national burden of elderly myocarditis (1992-2021) and projections of future disease burden trends
CONCLUSION: As of 2021, the ASIR(per 100,000) of myocarditis in the elderly population showed a decline compared to 1992; however, a recent upward trend has been identified. Considering ongoing population growth, the number of myocarditis cases among the elderly is anticipated to increase.
Epigenetic editing at individual age-associated CpGs affects the genome-wide epigenetic aging landscape
Aging is reflected by genome-wide DNA methylation changes, which form the basis of epigenetic clocks, but it is largely unclear how these epigenetic modifications are regulated and whether they directly affect the aging process. In this study, we performed epigenetic editing at age-associated CpG sites to explore the consequences of interfering with epigenetic clocks. CRISPR-guided editing targeted at individual age-related CpGs evoked genome-wide bystander effects, which were highly...
Prevalence and characteristics of older adults with type 2 diabetes mellitus living in French Caribbean nursing homes: results from the baseline KASEHPAD study
CONCLUSION: As the prevalence of older adults with T2DM is expected to rise in the Caribbean region, this trend will present significant challenges in delivering tailored care within future nursing home settings.
Change in Fall Status of Older People With Dementia and Caregiving Difficulties: Moderation Effects of Living Arrangements
OBJECTIVES: We aim to investigate the associations between 2-year fall status among community-dwelling older people with dementia and care partners' emotional, physical, and financial difficulties, with living arrangements (co-residence vs. separate residence) as a moderator.
Drug-Based Lifespan Extension in Mice Strongly Affects Lipids Across Six Organs
Caloric restriction is associated with slow aging in model organisms. Additionally, some drugs have also been shown to slow aging in rodents. To better understand metabolic mechanisms that are involved in increased lifespan, we analyzed metabolomic differences in six organs of 12-month-old mice using five interventions leading to extended longevity, specifically caloric restriction, 17-α estradiol, and caloric restriction mimetics rapamycin, canagliflozin, and acarbose. These interventions...
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