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Mitochondrial-nuclear crosstalk: A central axis in Alzheimer's disease

2 days 12 hours ago
Alzheimer's disease (AD) is a progressive neurodegenerative disorder traditionally defined by amyloid-β plaques and tau tangles. However, growing evidence indicates that deeper disruptions in cellular homeostasis contribute to disease onset and progression. Among these, impaired communication between mitochondria and the nucleus has emerged as a central yet underrecognized pathological feature. Mitochondrial-nuclear (mito-nuclear) crosstalk regulates energy metabolism, stress responses, and...
Kunal Samantaray

The PM20D1-OLE pathway induces microglia rewiring to ameliorate Alzheimer disease

2 days 12 hours ago
There is increasing evidence of microglia participation in Alzheimer's disease (AD), which incentives their modulation to intercept the disease. Here, we describe a new mechanism by which the recently AD-associated Peptidase M20 Domain Containing 1 (PM20D1) instructs microglia to tackle AD. We show that the PM20D1-derived N-oleoyl-Leucine (OLE) improves AD pathologies in two animal models of AD. OLE induces microglia association with amyloid beta (Aβ) plaques, reduce their size, number and...
Victoria Pozzi-Ruiz

D-pinitol extends the lifespan of Caenorhabditis elegans through integrated antioxidant defense, proteostasis, and autophagy signaling

2 days 12 hours ago
Aging is driven in part by progressive deterioration of proteostasis and antioxidant defense, leading to cellular dysfunction and age-associated disease. The naturally occurring methylated inositol D-pinitol (DP) was reported to present metabolic, antioxidant, and anti-inflammatory effects, as well as to extend the lifespan of D. melanogaster and C. elegans through the insulin/IGF-1 signaling pathway. But the mechanism of DP on delay aging remains poorly understand. Here, we showed that 200 μM...
Lin Shi

Mitochondrial-nuclear crosstalk: A central axis in Alzheimer's disease

2 days 12 hours ago
Alzheimer's disease (AD) is a progressive neurodegenerative disorder traditionally defined by amyloid-β plaques and tau tangles. However, growing evidence indicates that deeper disruptions in cellular homeostasis contribute to disease onset and progression. Among these, impaired communication between mitochondria and the nucleus has emerged as a central yet underrecognized pathological feature. Mitochondrial-nuclear (mito-nuclear) crosstalk regulates energy metabolism, stress responses, and...
Kunal Samantaray

Sarcopenia promotes tumorigenesis by disrupting NOTCH-SDC2-regulated biogenesis of muscle-derived extracellular vesicles

2 days 12 hours ago
Sarcopenia is an age-related condition characterized by loss of skeletal muscle mass and strength and is associated with increased cancer incidence and mortality, yet how muscle decline promotes tumorigenesis remains unclear. Here, we show that skeletal muscle functions as an anti-tumor organ by secreting extracellular vesicles (EVs) that suppress tumor growth. Using Drosophila melanogaster and mouse cancer models, we demonstrate that muscle-derived EVs inhibit tumorigenesis. In contrast,...
Kah Yong Goh

Atomic structures of medin and Aβ fibrils reveal polymorphic remodeling in mixed amyloid systems

2 days 12 hours ago
Amyloid assembly in vivo occurs in complex environments where multiple aggregation-prone species coexist. Aβ and medin are prevalent amyloids in ageing humans that co-localize in cerebral amyloid angiopathy (CAA), yet their structural interactions remain poorly understood. Here, using cryo-electron microscopy, we determine high-resolution fibril structures from in vitro mixtures of Aβ40 and medin. From the same reaction, we resolve three distinct fibril populations: (i) a previously...
Brajabandhu Pradhan

D-pinitol extends the lifespan of Caenorhabditis elegans through integrated antioxidant defense, proteostasis, and autophagy signaling

2 days 12 hours ago
Aging is driven in part by progressive deterioration of proteostasis and antioxidant defense, leading to cellular dysfunction and age-associated disease. The naturally occurring methylated inositol D-pinitol (DP) was reported to present metabolic, antioxidant, and anti-inflammatory effects, as well as to extend the lifespan of D. melanogaster and C. elegans through the insulin/IGF-1 signaling pathway. But the mechanism of DP on delay aging remains poorly understand. Here, we showed that 200 μM...
Lin Shi

Hopx(+) optic nerve head-astrocytes counter neuronal stress and glaucoma damage

2 days 12 hours ago
Retinal ganglion cell (RGC) axons form the optic nerve (ON). Numerous age-related ON diseases, including glaucoma, the second most common cause of worldwide blindness, result from multiple RGC stressors. Nearly all ON astrocytes in the optic nerve head (ONH): the junctional region between the ON and the retina in young-adult rodents expresses the homeodomain only (Hopx) protein. Hopx(+) ONH astrocytes are depleted during aging. ONH primary cultures which include Hopx(+) astrocytes secrete...
Steven L Bernstein

Unveiling the glymphatic system's role in brain aging: A comprehensive biomarker and modifiable intervention target

2 days 12 hours ago
The focus of this study is to investigate the role of diffusion tensor imaging along the perivascular space (DTI-ALPS) index in brain aging. To address this, we first examined the association of DTI-ALPS with aging hallmarks among 40,488 UK Biobank (UKB) participants. Next, we developed normative brain age models incorporating the DTI-ALPS index from 12,401 healthy UKB adults and validated in UKB-ADNI and UKB-TALENT datasets. Finally, we explored the relationship between brain age gap (BAG) with...
Yuanyuan Fang

Short-Term Dietary Intervention Alters Physiological Profiles Relevant to Ageing

2 days 12 hours ago
Ageing is a complex process influenced by modifiable factors such as diet, which may accelerate or decelerate physiological decline. While chronological age increases uniformly, biological ageing varies between individuals, reflecting differences in health status and the resilience of biological systems. The Klemera-Doubal Method (KDM), a composite biomarker-based index often used as an estimate of biological age, has been associated with morbidity and mortality in large cohorts. This study...
Caitlin J Andrews

Processing speed moderates the relationship between age and crystallized intelligence and influences the indirect effect of age on verbal working memory in middle-aged and older adults

2 days 12 hours ago
This study examined the extent to which processing speed moderates the relationship between age and crystallized intelligence and influences the indirect effect of age on verbal working memory in 233 healthy middle and older adults aged 51-94 years. Participants were screened for cognitive impairment and depressive symptoms before completing a battery of cognitive tests. Data were analyzed using moderated mediation models with bootstrapping. Correlational analyses revealed significant negative...
Julio Menor