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Repetitive DNA sequences can adopt alternative (i.e., non-B) DNA structures, which represent an endogenous source of genetic instability. Z-DNA, a non-B-DNA structure, has been implicated in the development of age-related genetic disorders such as cancer and Alzheimer's disease. Previously, we found that Z-DNA is mutagenic in mammals; however, the impact of age on Z-DNA-induced genetic instability has not yet been explored. Here, we investigated the effects of aging on Z-DNA-induced genetic...

Repetitive DNA sequences can adopt alternative (i.e., non-B) DNA structures, which represent an endogenous source of genetic instability. Z-DNA, a non-B-DNA structure, has been implicated in the development of age-related genetic disorders such as cancer and Alzheimer's disease. Previously, we found that Z-DNA is mutagenic in mammals; however, the impact of age on Z-DNA-induced genetic instability has not yet been explored. Here, we investigated the effects of aging on Z-DNA-induced genetic...

CONCLUSIONS: Abdominal obesity control may reduce CVD incidence and mortality, thereby shifting the disease burden toward dementia and FI due to increased longevity, highlighting the need for integrated, life-course public health strategies responsive to the patterns of dementia and its comorbidity in older people.

No abstract

In the context of population aging, musculoskeletal fitness has emerged as a cornerstone of overall well-being and injury prevention, relying on the coordinated function of cartilage, bone, and muscle. Drawing on the principle of "increasing income and reducing expenditure," we propose a combinatorial formulation consisting of the nicotinamide adenine dinucleotide (NAD) precursor nicotinamide mononucleotide (NMN) and the NAD^(+)-consuming enzyme inhibitor apigenin (API), hereafter referred to as...

This study examined the associations of biological age accelerations (BAAs)-KDM-BA acceleration (via Klemera and Doubal's method) and PhenoAge acceleration (epigenetics-based), defined as residuals from regressing each biological age estimate on chronological age (CA)-with multimorbidity progression (measured by the Charlson Comorbidity Index, CCI), compared to CA. Utilizing UK Biobank data (n = 317,835; median follow-up: 13 years), Cox regression models adjusted for sex, ethnicity, lifestyle,...

The proteinopathy of the RNA-binding protein TDP-43, characterized by nuclear clearance and cytoplasmic inclusion, is a hallmark of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). Through CRISPR interference (CRISPRi) screening in human neurons, we identified the decapping scavenger enzyme (DCPS) as a novel genetic modifier of TDP-43 loss-of-function (LOF)-mediated neurotoxicity. Our findings reveal...

Tapping already strained budgets, Genesis Mission gives scientists just weeks to apply for first awards

First crewed Moon mission since 1972 caught extraordinary glimpses of lunar terrain

Fluid-filled soda cans confirm a long-untested theory of pattern formation

Some trees in southern Japan are already failing to reach peak bloom—a trend researchers predict will move north in the coming decades