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DeepDrugDiscovery identifies blood-brain barrier permeable autophagy enhancers for Alzheimer's disease
Dysfunctional autophagy, a key cellular cleaning process, is a key driver of brain ageing and neurodegenerative diseases such as Alzheimer's disease (AD). However, developing effective treatments by enhancing autophagy has been challenging, as most known compounds act through the broad mTOR pathway, risking side effects, and few can effectively penetrate the brain. To address this, we developed DeepDrugDiscovery-a mechanism-aware, AI-powered screening platform incorporating ADMET and blood-brain...
Epigenetic adaptation of beta cells across lifespan and disease
Although the prevalence of type 2 diabetes (T2D) increases with age, most adults maintain normoglycaemia despite rising insulin resistance owing to the adaptive capacity of pancreatic beta cells to meet increased metabolic demand. However, persistent insulin resistance can lead to beta cell dysfunction and T2D onset. Here we show the mapping of genome-wide DNA methylation (DNAm) patterns and the epigenomic basis of beta cell adaptations by leveraging cell-type-specific methylome data from the...
Vitamin B12 improves skeletal muscle mitochondrial biology in aged mice
Age-related skeletal muscle deterioration is a commonly reported disability among older adults, attributed to several factors including mitochondrial dysfunction, a major hallmark of aging. Therapies to attenuate or reverse mitochondrial decline are limited. Despite identified positive relationships between vitamin B12 (B12) and mitochondrial biology, the impact of B12 supplementation on skeletal muscle mitochondria, in advanced age, has not been examined. Thus, the impact of B12 supplementation...
Lactoperoxidase is a candidate for mediating neuromelanin formation in the human substantia nigra
The presence of neuromelanin is a characteristic feature of the human substantia nigra (SN); however, the mechanism of its synthesis and its role in the development of Parkinson's disease remain unclear. Here, we report that the host defense enzyme lactoperoxidase (LPO), which possesses broad antimicrobial activity on mucosal surfaces, is selectively expressed in human dopaminergic neurons, a feature not shared by the rodent SN. We also demonstrate that LPO can catalyze multiple steps of melanin...
Inflammaging in aged tissues drives remodeling of the CD8<sup>+</sup> T cell compartment
Aging strongly impacts CD8^(+) T cells, including the loss of naive cells and the emergence of age-associated GZMK^(+)CD8^(+) T cells (T(AA) cells). Although T(AA) cells constitute a major population in aged mice, the pathway underlying their differentiation remains unknown. Here, we demonstrate that T(AA) cell development is cell extrinsic and requires antigen exposure within aged non-lymphoid tissues. Using a TNF^(Δ69AU/+) mouse model, we show that low-grade inflammation accelerates CD8^(+) T...
Do Care Coordinators Improve the Quality of Healthcare for Older Adults in the U.S.?
ObjectiveThis study examined whether older adults with informal, professional, or both types of care coordinators (CCs) reported different healthcare quality than those without CCs.MethodsData came from the 2016 Health and Retirement Study (n = 1,555) Module 10 on coordinated care. CC type and the helpfulness of professional CCs were independent variables. Outcomes included perceived confusion about care, conflicting advice from different providers, care satisfaction, and person-centered care....
Cross-species characterisation of microglial morphology and proliferation during ageing
By 2050, one-fifth of the world is expected to be over 60, and the prevalence of age-related neurological conditions is predicted to increase dramatically. Aged animals are currently underutilised in neurological research, leading to a gap in knowledge about the contribution of biological age to the pathophysiology of age-related neurological conditions. Additionally, it is unclear whether age-related changes differ across species used in preclinical models, and how these differences may compare...
The 'mitochondrial guardian' α-amyrin links colourful fruit consumption to cognitive resilience
Mitochondrial quality control is essential for maintaining neuronal function and resilience during aging, yet pharmacological strategies that effectively restore mitophagy to maintain mitochondrial homeostasis remain limited. Emerging evidence suggests that dietary molecules may influence mitochondrial health, although the underlying mechanisms are largely unknown. Here, we summarize our recent finding whereby we have identified a robust mitophagy inducer: α-amyrin (αA). This molecule is a...
Volunteer Leadership in Older Adults' Self-Guided Learning Groups in Taiwan: Motivations and Management Processes Through an Ecological Lens
As global populations age, active aging and lifelong learning have become critical policy objectives. In Taiwan, the Ministry of Education (MOE) promotes Older Adults' Self-Guided Learning Groups (OASLGs); however, the sustainability of these groups relies heavily on volunteer leaders. This study investigates the motivations and management processes of "Excellent Leaders" in OASLGs using a qualitative approach. Drawing on Bronfenbrenner's ecological systems theory, we analyzed semistructured...