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Rab27b promotes lysosomal function and alpha-synuclein clearance in neurons

1 month 1 week ago
Alpha-synuclein (αsyn) is the key pathogenic protein implicated in synucleinopathies including Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). In these diseases, αsyn is thought to spread between cells where it accumulates and induces pathology; however, mechanisms that drive its propagation or aggregation are poorly understood. We have previously reported that the small GTPase Rab27b is elevated in human PD and DLB and that it can mediate the autophagic clearance and toxicity of...
Kasandra Scholz

Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST

1 month 1 week ago
Ergothioneine (EGT) is a diet-derived, atypical amino acid that accumulates to high levels in human tissues. Reduced EGT levels have been linked to age-related disorders, including neurodegenerative and cardiovascular diseases, while EGT supplementation is protective in a broad range of disease and aging models. Despite these promising data, the direct and physiologically relevant molecular target of EGT has remained elusive. Here, we use a systematic approach to identify how mitochondria...
Hans-Georg Sprenger

HypoxyStat, a small-molecule form of hypoxia therapy that increases oxygen-hemoglobin affinity

1 month 1 week ago
We have previously demonstrated that chronic inhaled hypoxia is remarkably therapeutic in the premier animal model of mitochondrial Leigh syndrome, the Ndufs4 knockout (KO) mouse. Subsequent work has extended this finding to additional mitochondrial diseases and more common conditions. However, challenges inherent to gas-based therapies have hindered the rapid translation of our findings to the clinic. Here, we tested a small molecule (hereafter termed HypoxyStat) that increases the binding...
Skyler Y Blume

Regulatory Roles of Exosomes in Aging and Aging-Related Diseases

1 month 1 week ago
Exosomes are small vesicles with diameters ranging from 30 to 150 nm. They originate from cellular endocytic systems. These vesicles contain a rich payload of biomolecules, including proteins, nucleic acids, lipids, and metabolic products. Exosomes mediate intercellular communication and are key regulators of a diverse array of biological processes, such as oxidative stress and chronic inflammation. Furthermore, exosomes have been implicated in the pathogenesis of infectious diseases, autoimmune...
Nanyin Xiao

Immune genes involved in synaptic plasticity during early postnatal brain development contribute to post-stroke damage in the aging male rat brain

1 month 1 week ago
Stroke remains a leading cause of mortality and long-term disability worldwide, underscoring the urgent need to identify novel therapeutic targets to enhance brain circuitry repair and functional recovery. This study explores the concept of longevity assurance genes, which primarily function within genetic pathways responsible for repair and maintenance. These pathways encompass molecular and metabolic processes as well as organ- and system-level functions. To investigate this, we employed...
Denisa F V Pirscoveanu

Intact embodiment during perspective-taking in older adults is not affected by focal tDCS

1 month 1 week ago
Embodied processing is crucial for visual perspective taking (VPT), with evidence from non-invasive transcranial direct current stimulation (tDCS) suggesting a causal role of the right temporoparietal junction (rTPJ). However, it is not known whether such embodied factors are maintained in older adults or whether rTPJ-tDCS has comparable effects in advanced age. We employed a balanced and sham-tDCS controlled, double-blinded, cross-over design, including two randomized experimental groups of...
Mandy Roheger

Innovations in aging biology: highlights from the ARDD emerging science & technologies workshop

1 month 1 week ago
The field of biogerontology has established itself through significant lines of research in recent decades. However, despite early breakthroughs, progress in understanding the aging process has been slow. To push the field forward, new methodologies and technologies are likely needed to unravel the complexity of aging. This meeting brought together leading scientists and innovators to explore some emerging approaches, presenting groundbreaking advancements in four key sessions, culminating in a...
Maximilian Unfried

ImmuneLENS characterizes systemic immune dysregulation in aging and cancer

1 month 1 week ago
Recognition and elimination of pathogens and cancer cells depend on the adaptive immune system. Thus, accurate quantification of immune subsets is vital for precision medicine. We present immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS), which estimates T cell and B cell fractions, class switching and clonotype diversity from whole-genome sequencing data at depths as low as 5× coverage. By applying ImmuneLENS to the 100,000 Genomes Project, we identify genes enriched with...
Robert Bentham

The cholesterol 24-hydroxylase CYP46A1 promotes alpha-synuclein pathology in Parkinson's disease

1 month 1 week ago
Parkinson's disease (PD) is a neurodegenerative disease characterized by the death of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies that are composed of aggregated α-synuclein (α-Syn). However, the factors that regulate α-Syn pathology and nigrostriatal dopaminergic degeneration remain poorly understood. Previous studies demonstrate cholesterol 24-hydroxylase (CYP46A1) increases the risk for PD. Moreover, 24-hydroxycholesterol (24-OHC), a brain-specific oxysterol...
Lijun Dai