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Daily briefing: Why women are far more likely to develop Alzheimer's than men
No abstract
Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease
Ageing is the most prominent risk factor for Alzheimer's disease (AD). However, the cellular mechanisms linking neuronal proteostasis decline to the characteristic aberrant protein deposits in the brains of patients with AD remain elusive. Here we develop transdifferentiated neurons (tNeurons) from human dermal fibroblasts as a neuronal model that retains ageing hallmarks and exhibits AD-linked vulnerabilities. Remarkably, AD tNeurons accumulate proteotoxic deposits, including phospho-tau and...
Lysosome repair fails in ageing and Alzheimer's disease
No abstract
Blood-based biomarkers of Alzheimer's disease and incident dementia in the community
Evidence regarding the clinical validity of blood biomarkers of Alzheimer's disease (AD) in the general population is limited. We estimated the hazard and predictive performance of six AD blood biomarkers for incident all-cause and AD dementia-the ratio of amyloid-β 42 to amyloid-β 40 and levels of tau phosphorylated at T217 (p-tau217), tau phosphorylated at T181 (p-tau181), total tau, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP)-in a cohort of 2,148 dementia-free...
R406 and its structural analogs reduce SNCA/α-synuclein levels via autophagic degradation
The presence of neuronal Lewy bodies mainly composed of SNCA/α-synuclein aggregations is a pathological feature of Parkinson disease (PD), whereas reducing SNCA protein levels may slow the progression of this disease. We hypothesized that compounds enhancing SNCA's interaction with MAP1LC3/LC3 May increase its macroautophagic/autophagic degradation. Here, we conducted small molecule microarray (SMM)-based screening to identify such compounds and revealed that the compound R406 could decrease...
Growth hormone-deficient Ames dwarf mice resist sarcopenia and exhibit enhanced endurance running performance at 24 months
Ames dwarf mice (df/df) live 50% longer than normal littermates due to a genetic defect in growth hormone (GH) signaling. The enhanced longevity of Ames dwarfs has been studied extensively in an endocrinological context of cellular metabolism and increased resistance to oxidative stress (Bartke. World J Mens Health 37(1):19, 8; Bartke 2; BartkeJ Am Aging Assoc 23(4):219, 10; Bartke. World J Mens Health 39(3):454-465, 11; Brown-Borg et al. Nature 384(6604):33-33, 1; Masternak et al. 2018)....
Impact of BRCA mutations, age, surgical indication, and hormone status on the molecular phenotype of the human Fallopian tube
The human Fallopian tube (FT) is an important organ in the female reproductive system and has been implicated as a site of origin for pelvic serous cancers, including high-grade serous tubo-ovarian carcinoma (HGSC). We have generated comprehensive whole-genome bisulfite sequencing, RNA-seq, and proteomic data of over 100 human FTs, with detailed clinical covariate annotations. Our results challenge existing paradigms that extensive epigenetic, transcriptomic and proteomic alterations exist in...
Butylphthalide identified via Samul-tang-induced transcriptomic signatures improves oocyte quality in aged mice
Samul-tang (SM) is a traditional prescription widely used in clinical practice for the management of gynecological diseases, especially for menstrual regulation and infertility treatment. We previously reported its efficacy in increasing mature oocyte production and improving ovarian reserves, potentially regulated by rat sarcoma virus (Ras) signaling in the ovaries of aged mice. Although the main ingredients of SM are known, the bioactive compounds responsible for protecting ovarian function...
Empower families to lead the design of their ageing loved ones' health care
No abstract
Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease
Ageing is the most prominent risk factor for Alzheimer's disease (AD). However, the cellular mechanisms linking neuronal proteostasis decline to the characteristic aberrant protein deposits in the brains of patients with AD remain elusive. Here we develop transdifferentiated neurons (tNeurons) from human dermal fibroblasts as a neuronal model that retains ageing hallmarks and exhibits AD-linked vulnerabilities. Remarkably, AD tNeurons accumulate proteotoxic deposits, including phospho-tau and...
Lysosome repair fails in ageing and Alzheimer's disease
No abstract
Optimization of adeno-associated viral (AAV) gene therapies vectors for balancing efficacy, longevity and safety for clinical application
Adeno-associated viral (AAV) vectors are an ideal platform for gene therapy due to their ability to deliver therapeutic cargos safely and effectively across various target organs. Their low immunogenicity contributes to long-lasting therapeutic effects. However, recent insights highlight the significance of CpG content within AAV vectors, where unmethylated CpG dinucleotides can trigger a TLR9-mediated immune response, leading to the rapid elimination of transduced cells. Clinical evidence...
Osteoporosis risk and its association with all-cause and cause-specific mortality among the elderly: a 16-year nationwide cohort study
CONCLUSIONS: The risk of osteoporosis is independently associated with the prediction of mortality. The OSTA may serve as a suitable predictor for mortality related to osteoporosis among the Asian population.
Impact of physical activity on the depression and self-care ability among Chinese older adults during the COVID-19 pandemic: propensity score matching analysis
CONCLUSION: Moderate and light physical activity in older adults alleviates depression and improves instrumental activities of daily living (IADLs), and light physical activity improves the level of activities of daily living (ADLs).