Aggregator

The molecular circadian clock is a ubiquitous transcriptional-translational feedback loop that regulates CNS function, glial responses, and neurodegenerative pathology. The nuclear receptors REV-ERB-α (Nr1d1) and REV-ERB-β (Nr1d2) are components of the core circadian clock which regulate metabolism, neuroinflammatory responses, synaptic pruning, and protein aggregation, though the cell type-specific effects and relative compensatory effects of REV-ERB-α AND -β in the brain are unknown. To study...

Cytokines and their receptors play important roles in brain development and aging-related disease, but their functions within the healthy adult brain remain poorly understood. Here, we show that pyramidal neurons in hippocampal CA1 induce Fn14 expression in response to activity and environmental enrichment. Once expressed, Fn14 dampens the activity of these neurons most prominently at the daily transition between light and dark. Fn14 expression in CA1 neurons is regulated by the circadian...

Nicotinamide adenine dinucleotide (NAD^(+)) levels decline with age, which has been associated with the development of aging-associated diseases. However, it remains unknown whether low NAD^(+) levels in early life affect aging. This study demonstrates that deficiency of NAD synthetase (NADS), a critical enzyme of the deamidated NAD^(+) biosynthesis pathway, drastically reduced NAD^(+) levels in skeletal muscle and impaired muscle function at a young age. Intriguingly, NAD^(+) levels were...

Energy metabolism involves a series of biochemical reactions that generate ATP, utilizing substrates such as glucose and oxygen supplied via cerebral blood flow. Energy substrates are metabolized in multiple interrelated pathways that are cell- and organelle-specific. These pathways not only generate energy but are also fundamental to the production of essential biomolecules required for neuronal function and survival. How these complex biochemical processes are spatially distributed across the...

Dysregulation of the adaptive immune system is a key feature of aging and is associated with age-related chronic diseases and mortality. Here, we find that T cell aging, especially in the CD4 subset, is controlled by B cells. B cells contributed to the age-related reduction of naive CD4 T cells, their differentiation toward immunosenescent T cell subsets, and age-associated T cell receptor clonal restriction. Concurrently, mice lacking B cells displayed improvements in health span and life span....

The elegant work by Maejima et al. recently published in Aging Cell reveals a previously unrecognized mechanism linking age-related oxytocin (OXT) decline to epigenetic remodeling, mitochondrial dysfunction, and systemic inflammation (Maejima et al. 2025). Beyond documenting this relationship, the authors demonstrate its remarkable reversibility through nasal OXT administration. These findings provide the first molecular evidence supporting what has long been proposed: that the OXT system...

A newly identified specific category of non-coding RNA (ncRNA), circRNAs, is drawing interest for their role in controlling several biological processes including muscle regeneration, aging, and adaptation to physical activity. Unlike linear RNAs, circRNAs are very stable and can have long-lasting regulatory impact since they create a covalently closed loop structure. Emerging evidence indicates that circRNAs play a pivotal role in skeletal muscle biology by regulating myogenesis, satellite cell...

Episodic sequence memory is crucial for daily functioning and typically declines during aging. However, the neural mechanisms underlying this decline remain poorly understood. We examined the resting-state functional connectivity (FC) correlates of sequence memory in healthy older adults (OA), with a young adult (YA) group included for comparison. Thirty-eight OA (mean ± SD age: 69.9 ± 3.9 years; 24 women) and 20 YA (mean ± SD age: 24.2 ± 3.4 years; 14 women) completed a sequence memory task and...

No abstract

To maintain protein homeostasis, which is essential for health, animals have developed complex protective mechanisms against various acute and chronic stresses. However, the coordination of responses to these protein stresses, especially their age-dependent changes, is not well understood. HSF-1 is a key regulator of protein homeostasis. Our study identifies PBS-7, a proteasome subunit, as its crucial regulator. In aged C. elegans, decreased PBS-7 binding reduces proteasome-mediated degradation...

CONCLUSION: Ubiquitination modification, autophagy process, cellular senescence and nervous system regulation may jointly contribute to the core molecular mechanism of ARHL. The hsa-miR-100-5p, hsa-miR-23b-3p, hsa-miR-373-3p, and hsa-miR-27b-3p may preliminarily act as key regulatory factors to participate in the pathophysiological process of ARHL, providing exploratory evidence for their potential application value as molecular markers.