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RNA G-quadruplexes (rG4s) are stable secondary structures formed by guanine-rich RNA sequences that have emerged as critical regulators of RNA metabolism. The rG4s are widespread in both coding and noncoding RNAs and have been implicated in regulation multiple post-transcriptional processes, including RNA stability, splicing, polyadenylation, nuclear export, localization, and translation. Recent findings real that rG4s play pathological roles in neurodegenerative diseases (NDs), including...

Defective nucleocytoplasmic transport (NCT) has emerged as a contributing factor in the pathogenesis of neurodegenerative diseases and aging. Valosin-containing protein (VCP) is an AAA+ATPase required for disassembly of protein complexes, and mutations in VCP cause neurodegenerative and neuromuscular diseases. We find that VCP is required for quality control of nuclear pore complexes (NPCs) by extracting selected nucleoporins from NPCs for proteasome-mediated degradation. Pathogenic VCP variants...

CONCLUSION: Our findings suggest a bidirectional relationship between MetS and EAA, with biological aging potentially mediating metabolic deterioration. EAA may serve as both a marker and mediator of metabolic health, and a promising target for prevention and intervention.

Insulin action on the skeleton is essential for bone development and whole-body energy metabolism, however a global view of signaling in this tissue is lacking. Furthermore, whether there are signaling differences that drive the gene-specific activation under insulin-resistant (IR) or ageing conditions is unknown. Here, we perform a phosphoproteomic analysis of insulin signaling in the bones of young, lean, insulin-sensitive versus old, obese, IR mice revealing a rewiring of phosphorylation. We...

Anopheles gambiae is one of the principal vectors of human malaria. Over the past two decades, transgenic mosquito strains have been essential tools for studying mosquito biology and developing genetic control strategies such as gene drives. Mosquito transformants are typically identified using fluorescent markers, which are assumed to be phenotypically neutral. While generating CRISPR-based gene drive strains carrying an OpIE2-DsRed marker we unexpectedly found that transgenic females were...

CONCLUSIONS: ε4 contributes to literacy decline among older adults, presumably due in part to the accumulation of neuropathologies associated with ε4. We discuss the potential clinical implications of ε4-related literacy decline.

CONCLUSIONS: A decision support tool for caregivers of PLwD that provides education about transitions in care site, along with support for the emotional aspects of decision making, is highly acceptable and supports caregivers' ability to engage with what can be a challenging topic.

CONCLUSIONS: In the Rugao Aging Cohort, significant gender differences of thickness of all macular layers between males and females were identified, with males exhibiting thicker inner rings and thinner outer rings compared to females. Notably, cognitive decline was associated with the thinning of the central part and inner ring of macula exclusively in females. These results suggest that when macular thickness is used as a risk marker for cognitive decline, its gender bias should be carefully...

Memory functions are susceptible to age-related cognitive decline, making it essential to explore the underlying neurophysiological mechanisms that contribute to memory function during healthy ageing. Resting-state EEG (rsEEG) parameters, particularly the aperiodic exponent, a marker of cortical excitation-inhibition balance, and individual alpha peak frequency, a correlate of neural processing efficiency, have demonstrated associations with ageing and cognitive functions. This study...

Aging is a progressive process characterized by cellular and molecular damage leading to mitochondrial dysfunction and cognitive decline. Mitochondrial dysfunction is a critical factor in memory impairment in aging and neurodegenerative diseases. While sex differences in aging have been observed across various species, the underlying cellular and molecular mechanisms remain poorly understood, mainly focused on mitochondrial proteostasis. This study examined hippocampal-dependent cognitive...

CONCLUSIONS: The population of nonagenarians was specific in causes of death and comorbidities. Improving end-of-life care for these patients can include a high access to specialist palliative care and symptoms management.

Chemotherapy-induced bone loss is a debilitating and common side effect of cancer treatment, though its underlying mechanisms remain poorly understood. Here, we show that, despite the systemic administration of chemotherapy, cellular senescence is restricted to bone marrow adipo-lineage cells specifically Cxcl12-abundant reticular (CAR) cells and bone marrow adipocytes (BMAds). Induction of senescence within these populations promotes RANK ligand (RANKL)-mediated osteoclastogenesis, leading to...