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BACKGROUND: Given trends towards greater life expectancy, there is an increasing need to promote healthy ageing and add quality and value to older adults' lives, however the evidence regarding the effects on overall health and wellbeing has not been synthesised. Active lifestyles may provide diverse health and wellbeing benefits for older adults in terms of maintaining or improving their physical, psychological, and social functions. This systematic review evaluates whether and how different...

Post-translational modifications (PTMs) regulate protein homeostasis, but how aging impacts PTMs remains unclear. Here, we used mass spectrometry to reveal changes in hundreds of protein ubiquitylation, acetylation, and phosphorylation sites in the mouse aging brain. We show that aging has a major impact on protein ubiquitylation. 29% of the quantified ubiquitylation sites were affected independently of protein abundance, indicating altered PTM stoichiometry. Using iPSC-derived neurons, we...

Ceramic circuit boards (CCBs) have been extensively utilized in 5G communications, aerospace, and artificial intelligence due to their excellent thermal conductivity and electrical performance. However, due to the limitation of manufacturing technologies, the existing CCBs can not take into account both the resolution and thickness, which restricts the miniaturization and high power of the resulting electronics. Herein, we report a standing-CCBs (S-CCBs) with both high-resolution and high...

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Disruption in neuronal and synaptic metabolic homeostasis is a key driver of neurodegeneration in Parkinson's disease (PD). Mitochondrial activity, biomass, and efficiency are critical to this balance. While activity and biomass are well characterized in PD pathology, mitochondrial metabolic efficiency remains insufficiently explored. Our previous studies showed that the protein product of PD-associated gene DJ-1 modulates metabolic efficiency through its interaction with the F1Fo-ATP-synthase β...

Duplication of the SNCA gene (SNCA^(Dupl)), linked to elevated levels of α-synuclein (aSyn), is a genetic cause of Parkinson's disease (PD). Our prior work with human-induced pluripotent stem cell (hiPSC)-derived midbrain neurons generated from patients with PD SNCA^(Dupl) identified neuritic deficits, accompanied by decreased levels of cytoskeletal element β-tubulin-III (bTubIII). To explore mechanisms underlying these effects in SNCA^(Dupl) neurons, we used CRISPR-Cas9 to generate isogenic...

The focus of aging research has shifted from increasing lifespan to enhancing healthspan to reduce the time spent living with disability. Despite significant efforts to develop biomarkers of aging, few studies have focused on biomarkers of healthspan. We developed a proteomics-based signature of healthspan [healthspan proteomic score (HPS)] using proteomic data from the Olink Explore 3072 assay in the UK Biobank Pharma Proteomics Project (53,018 individuals and 2,920 proteins). A lower HPS was...

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CD8^(+) T cells exhibit distinct changes with aging, including a diminished naïve cell pool, an expansion of memory and exhausted cells, and altered effector molecule production, altogether leading to increased susceptibility to infection. They have reduced cytotoxicity in vivo, but increased granule content and faster cytotoxic kinetics to target cells in vitro. Whether CD8^(+) T cells from old mice degranulate when activated in vivo, within the aged environment, is unknown. This study...

Gait alterations are recognized as early markers of age-related decline and cognitive impairment. Dual-task assessments, which impose cognitive load while walking, provide valuable insights into gait control limitations and cognitive-motor interactions in aging populations. This study evaluates age-related and cognitive load-induced changes in gait parameters, with a particular focus on asymmetry, and aims to optimize the gait assessment protocol for the Semmelweis Study framework. The...

The age-associated neurodegenerative disorder, Lewy body dementia (LBD), encompasses neuropsychiatric symptom-overlapping Dementia with Lewy bodies (DLB) and Parkinson's Disease with Dementia (PDD). We characterised how differential mitochondrial DNA (mtDNA) profiles contribute to neurotype-specific neurodegeneration and thereby clinicopathological heterogeneity, between LBD's syndromes. We further characterised key nuclear-encoding genes' recalibrations in response to such mtDNA changes. In...

Multiple studies in mice with genetically disrupted growth hormone (GH) signaling have demonstrated that such disruption results in reduced body size, robustly increased longevity (> 50% in some cases), and improvements across multiple health parameters. However, it remains unclear how generalizable these findings are across mammals. Evidence in rats is limited and inconsistent. These conflicting results highlight the need for further investigation into the role of GH signaling in longevity...

CONCLUSIONS: Frailty trajectories at the end of life varied by cause of death, with neurodegenerative disease decedents exhibiting more severe frailty. These findings underscored the need for early identification of frailty and tailored end-of-life care strategies, particularly for individuals with neurodegenerative diseases who often experienced prolonged and severe frailty.

CONCLUSION: Despite trends of decreased functional specialization in aging, and prior evidence within this cohort of broad task-related activation and connectivity bilaterally, semantic task relevance remained uniquely localized to left hemisphere semantic network hubs. Increased coherence within DAN and DMN during rhyme blocks may reflect novelty of the rhyming task, underscoring flexible network recruitment for demanding tasks in healthy aging. Findings contribute to our understanding of...

CONCLUSIONS: Markers of inflammation were associated with multisensory impairment, but there were fewer associations with individual sensory impairments.