Poltorak, A. | bioRxiv Science

bioRxiv2024

Time-Resolved Neural Oscillations Across Sleep Stages: Associations with Sleep Quality and Aging

Sleep is a fundamental physiological process critical to cognitive function, memory consolidation, emotional regulation, and overall health. This study investigates the relationship between EEG spectral power dynamics and key sleep metrics, including percentage of N3, biological age, percentage of REM, and total sleep time (TST). Using high-resolution spectral analysis, we examine how power across multiple frequency bands (0.1-50 Hz) evolves temporally across sleep stages and influences sleep architecture. Our results reveal an inverse relationship between high-frequency power (sigma, beta, and gamma) during the N1 and N2 stages and the subsequent percentage of N3, suggesting that excessive low-frequency power in N2 may disrupt the smooth progression into deep sleep. Additionally, we identify a negative correlation between low delta power (0.1-0.5 Hz) during N2 and both percentages of N3 and TST, challenging traditional views on the role of delta activity in sleep regulation. These findings advance the understanding of how brain activity across frequencies modulates sleep depth and duration, with implications for addressing age-related sleep declines. Statement of SignificanceThis research highlights novel insights into the relationships between EEG spectral power dynamics and sleep architecture, offering a deeper understanding of how brain activity influences critical sleep metrics such as N3 percentage, REM percentage, and total sleep time. By revealing unexpected findings, such as the inverse relationship between low-frequency power during N2 and N3 duration, this study challenges conventional sleep science paradigms. These findings have significant implications for addressing age-related sleep declines and designing brain-computer interfaces (BCIs) to optimize sleep. By targeting specific frequency bands and leveraging real-time feedback, this work paves the way for personalized, non-invasive sleep modulation therapies, revolutionizing clinical and home-based sleep interventions.

neuroscience↗

bioRxiv2024

STING promotes homeostatic maintenance of tissues and confers longevity with aging

Local immune processes within aging tissues are a significant driver of aging associated dysfunction, but tissue-autonomous pathways and cell types that modulate these responses remain poorly characterized. The cytosolic DNA sensing pathway, acting through cyclic GMP-AMP synthase (cGAS) and Stimulator of Interferon Genes (STING), is broadly expressed in tissues, and is poised to regulate local type I interferon (IFN-I)-dependent and independent inflammatory processes within tissues. Recent studies suggest that the cGAS/STING pathway may drive pathology in various in vitro and in vivo models of accelerated aging. To date, however, the role of the cGAS/STING pathway in physiological aging processes, in the absence of genetic drivers, has remained unexplored. This remains a relevant gap, as STING is ubiquitously expressed, implicated in multitudinous disorders, and loss of function polymorphisms of STING are highly prevalent in the human population (>50%). Here we reveal that, during physiological aging, STING-deficiency leads to a significant shortening of murine lifespan, increased pro-inflammatory serum cytokines and tissue infiltrates, as well as salient changes in histological composition and organization. We note that aging hearts, livers, and kidneys express distinct subsets of inflammatory, interferon-stimulated gene (ISG), and senescence genes, collectively comprising an immune fingerprint for each tissue. These distinctive patterns are largely imprinted by tissue-specific stromal and myeloid cells. Using cellular interaction network analyses, immunofluorescence, and histopathology data, we show that these immune fingerprints shape the tissue architecture and the landscape of cell-cell interactions in aging tissues. These age-associated immune fingerprints are grossly dysregulated with STING-deficiency, with key genes that define aging STING- sufficient tissues greatly diminished in the absence of STING. Changes in immune signatures are concomitant with a restructuring of the stromal and myeloid fractions, whereby cell:cell interactions are grossly altered and resulting in disorganization of tissue architecture in STING-deficient organs. This altered homeostasis in aging STING-deficient tissues is associated with a cross-tissue loss of homeostatic tissue-resident macrophage (TRM) populations in these tissues. Ex vivo analyses reveal that basal STING- signaling limits the susceptibility of TRMs to death-inducing stimuli and determines their in situ localization in tissue niches, thereby promoting tissue homeostasis. Collectively, these data upend the paradigm that cGAS/STING signaling is primarily pathological in aging and instead indicate that basal STING signaling sustains tissue function and supports organismal longevity. Critically, our study urges caution in the indiscriminate targeting of these pathways, which may result in unpredictable and pathological consequences for health during aging. HIGHLIGHTSO_LIAging tissues are associated with tissue-autonomous immune fingerprints, primarily driven by interactions of tissue stromal and myeloid populations. C_LIO_LISTING shapes these immune fingerprints of aging tissues in unexpected ways. C_LIO_LILoss of STING alters the location, numbers, and viability of tissue resident macrophages. C_LIO_LISTING signaling is critical for longer lifespans and maintenance of tissue architecture. C_LI

immunology↗