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The field of ageing science has gone through remarkable progress in recent decades, yet many fundamental questions remain unanswered or unexplored. Here we present a curated list of 100 open problems in ageing and longevity science. These questions were collected through community engagement and further analysed using Natural Language Processing to assess their prevalence in the literature and to identify both well-established and emerging research gaps. The final list is categorised into...

CONCLUSIONS: These results suggest that WM training can represent a promising approach to sustain older adults’ cognitive functioning and to modulate cortical plasticity, inducing long-lasting left-lateralized activation.

Low yields of dopamine neurons in human stem cell-derived neural grafts limit their potential for treating Parkinson's disease. Zhang et al.¹ develop a new three-dimensional differentiation method, informed and refined through careful clonal linage tracing of donor cells post-transplantation, to improve dopamine neuron purity of grafts, eliminating unwanted, off-target populations.

Telomere biology is important for aging and is the cause of the pathogenesis of many neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), stroke, and brain tumors. Telomere shortening is considered to play a role in neurodegeneration, immune senescence, and cerebrovascular dysfunction. Shorter leukocyte telomere length (LTL) is associated with increased risk and severity of stroke, poorer cognitive outcomes in AD, and increased...

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The diagnosis of Parkinson's disease (PD) is currently based on clinical criteria, centered on the characteristic motor syndrome. However, motor manifestations become evident only after a significant proportion of nigro-striatal dopaminergic neurons have already undergone neurodegeneration. The recent "NSD-ISS" and "SynNeurGe" research frameworks have proposed new biological diagnostic criteria focusing on α-synucleinopathy, neurodegeneration, and genetic biomarkers, independent of clinical...

Cellular senescence plays dual roles in precancer lesions: initially serving as a tumor-suppressive barrier within the epithelial compartment and later contributing to a pro-tumoral precancer tissue microenvironment (PreTME) via a sustained, paracrine secretome known as senescent-associated secretory phenotype (SASP). This commentary highlights the role of senescence across various PreTME cell types, explores emerging pharmacologic and lifestyle interception strategies, and outlines current...

Cytosolic translation activity is fine-tuned by environmental conditions primarily through signaling pathways that target translation initiation factors. Although mitochondria possess their own translation machinery, they lack an autonomous signaling network analogous to their cytosolic counterpart for regulating translation activity. Consequently, our understanding of how mitochondrial translation activity is adjusted under different metabolic environments remains very limited. Here, we report...

Aging is a natural, multifactorial biological process characterised by progressive cellular and tissue damage in response to various stressors, leading to functional decline that often affects multiple organs, contributing to the development of age-related diseases. Although life expectancy has increased significantly, age-related conditions have become the leading causes of impairment and disability in the elderly, becoming a major global health concern. This highlights the need for innovative,...

Telomere biology is important for aging and is the cause of the pathogenesis of many neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), stroke, and brain tumors. Telomere shortening is considered to play a role in neurodegeneration, immune senescence, and cerebrovascular dysfunction. Shorter leukocyte telomere length (LTL) is associated with increased risk and severity of stroke, poorer cognitive outcomes in AD, and increased...

Age-related hearing loss (ARHL) has been increasingly implicated as a contributor to cognitive decline, yet the structural neural mechanisms underlying this association remain unclear. This study investigates the relationship between hearing function, measured by pure-tone thresholds (PTT) and words-in-noise (WIN) recognition, and gray matter (GM) volume in auditory and non-auditory brain regions in the left and right cerebral hemispheres. We also examine whether GM volume mediates the...

Mitophagy is crucial for the selective autophagic degradation of damaged mitochondria, helping to maintain both mitochondrial and cellular homeostasis. Here, we report a fluoroalkylated polypyridinium that specifically targets mitochondria and exhibits high activity in mitophagy induction. The polymer effectively restores mitochondrial function and alleviates the inflammatory response in foam cells by activating mitophagy, and displays inherent red fluorescence under physiological conditions,...

Motoric cognitive risk (MCR) syndrome is defined by slow gait speed and cognitive complaints. This study aimed to identify objective gait, cognitive, and psychosocial markers that characterize MCR beyond its traditional criteria. 104 older adults were classified into four groups: healthy aging (n = 50), slow gait speed only (n = 31), cognitive complaints only (n = 13), and MCR (n = 10). Participants completed single- and dual-task gait assessments while wearing wearable gait sensors. The...

The disposable soma theory posits that there is a trade-off between reproduction and somatic maintenance. In support of this theory, we previously identified that pharmacological inhibition of the germline has widespread protective cell non-autonomous effects on cellular protein homeostasis in the model organism Caenorhabditis elegans. However, the cell non-autonomous effects of the germline on mitochondrial protein homeostasis are not well defined. Here, we use pharmacological or genetic...

CONCLUSION: This study provides a comprehensive analysis of the multifactorial determinants of old-age disability in Botswana. The findings underscore the need for integrated, multisectoral strategies that go beyond healthcare access to include educational equity, age-friendly infrastructure, digital inclusion, and gender-sensitive social protection. Policies must address not only individual risk but also household and community conditions that jointly shape disability outcomes. These insights...

CONCLUSIONS: The PFMS intervention is feasible and shows preliminary efficacy in certain aspects during the hospital-to-home transition for older adults with chronic disease. Future research should refine the intervention to better enhance patient participation in medication safety behaviours and self-efficacy.

BACKGROUND: This research was conducted to investigate the association between cognitive function and smartphone ownership among very old adults, a rapidly growing age group. Additionally, we conducted a longitudinal investigation as a sub-analysis to determine whether owning a smartphone affects the level of long-term care certification as a proxy outcome for cognitive decline.

Fucosylation, a major glycan modification, has been shown to influence neuronal and microglial mechanisms, but whether unconjugated free l-fucose can affect brain function is unknown. l-Fucose can be transported into cells and metabolized by fucokinase (FCSK) via the poorly understood salvage pathway. Using mouse hippocampal slices, we showed that l-fucose enhanced excitatory neurotransmission and long-term potentiation (LTP) through regulation of presynaptic release. Such effects required...

Impaired clearance of amyloid-β (Aβ) contributes to Alzheimer's disease (AD) pathogenesis, but its upstream modulators remain poorly defined. We report secreted Dickkopf (DKK) proteins-DKK1 through DKK4-as previously unrecognized ligands of low-density lipoprotein receptor-related protein 1 (LRP1), a principal Aβ clearance receptor. Analyses of cells derived from a patient with AD, postmortem tissue, and 5×FAD mice reveal that DKK1 and DKK3 are elevated in AD and reduce Aβ uptake and degradation...