Biology subjects

Lore, S.

Publications and source records attributed to Lore, S..

3 recordsLinked to original sources

bioRxiv2026

BrainYears: A functional EEG-based brain age clock enables intervention-ready measurements of brain aging

Biological brain aging is a major determinant of cognitive decline and neurodegenerative disease, yet scalable and intervention-ready brain aging biomarkers remain limited. Here, we develop an electroencephalography (EEG)-based brain age clock using machine learning trained on high-dimensional neural features across the adult lifespan. Using 643 features captured from a Sens.ai headset and controller device, the model predicts chronological age with high accuracy (Pearson r = 0.92; MAE = 4.43 years) and yields an interpretable set of age-informative neural features capturing functional signatures of brain aging. Unlike MRI-based approaches, this EEG-based clock is non-invasive, transportable, cost- effective and suitable for repeated at-home longitudinal measurement. Furthermore, in a longitudinal neuromodulation program, BrainYears-predicted brain age decreased by a mean of -5.18 years in the intervention group whereas a minimal-exposure comparison group showed no change on average (+0.07 years). Together, this work introduces a functional brain aging biomarker and an intervention-ready platform for quantifying brain age modulation.

bioinformatics↗

bioRxiv2025

Accumulation of SA-βGal High Cells in Human Naive T Cell Compartments Reveals a Stress-Adapted, Senescent-Like State

Aging is associated with a decline in immune function termed immunosenescence, characterized by accumulation of senescent-like immune cells and chronic inflammation, known as inflammaging. While senescence-associated {beta}-galactosidase (SA-{beta}Gal) activity is a well-established senescence marker, its functional significance and the precise cellular subsets affected within the T cell compartment remain unclear. Here, we identify and characterize a previously unrecognized subset of naive CD4 and CD8 T cells displaying high SA-{beta}Gal activity that significantly increases with age. Despite exhibiting hallmark features of senescence such as DNA damage, nuclear envelope disruption, loss of heterochromatin, and pronounced dysregulation of autophagy and lysosomal pathways, these SA-{beta}Gal-high naive T cells notably lack the canonical senescence marker p21CIP1 and retain robust proliferative capacity upon activation. Remarkably, naive CD4 SA-{beta}Gal-high T cells acquire cytotoxic properties including NK-like features, granzyme secretion, and the ability to induce paracrine DNA damage in endothelial cells. Mechanistically, we demonstrate that impaired autophagic flux contributes significantly to this phenotype. Our findings address critical knowledge gaps regarding the nature and functional plasticity of senescence-like states in naive T cells, highlighting a novel link between lysosomal-autophagic dysfunction, cellular stress adaptation, and inflammaging. Understanding this unique T cell population provides important insights into immune aging and offers potential targets to mitigate age-associated immune dysfunction and chronic inflammation.

immunology↗

bioRxiv2024

Utilizing blood single-cell transcriptomics to integrate intrinsic and systemic immune aging

Biomarkers of aging provide insight into the biological effects of interventions and diseases. However, most biomarkers today are based on measurements derived from bulk cell measurements, making it challenging to interpret whether an effect is due to changes in cell type composition (systemic factors) or a cell intrinsic effect. Single-cell RNA sequencing provides a unique platform to simultaneously compare aging-associated changes on both a cellular and bulk level. We first generated a single-cell combined automated human blood cell type and age predictor (clock) for six distinct human T cell subsets. We applied these tools to find acute COVID is associated with a shift in CD8+ cytotoxic cell proportions, while cell type proportions are stable in patients with HIV on long-term ART treatment (HIV+ART). Both COVID and HIV+ART were associated with an increase in naive CD8 T cell transcriptomic age. We further found our single-cell aging biomarker is linked to ribosomal gene expression and has a link to mean cellular transcript length. This study highlights the potential of single cell transcriptomic biomarkers for understanding how the human immune system is impacted by age-associated systemic changes in cell type composition and intrinsic cellular aging.

immunology↗