ImAge quantitates aging and rejuvenation.

For efficient, cost-effective and personalized healthcare, biomarkers that capture aspects of functional, biological aging, thus predicting disease risk and lifespan more accurately and reliably than chronological age, are essential. We developed an imaging-based chromatin and epigenetic age (ImAge) that captures intrinsic age-related trajectories of the spatial organization of chromatin and epigenetic marks in single nuclei, in mice. We show that such trajectories readily emerge as principal changes in each individual dataset without regression on chronological age, and that ImAge can be computed using several epigenetic marks and DNA labeling. We find that interventions known to affect biological aging induce corresponding effects on ImAge, including increased ImAge upon chemotherapy treatment and decreased ImAge upon caloric restriction and partial reprogramming by transient OSKM expression in liver and skeletal muscle. Further, ImAge readouts from chronologically identical mice inversely correlated with their locomotor activity, suggesting that ImAge may capture elements of biological and functional age. In sum, we developed ImAge, an imaging-based biomarker of aging with single-cell resolution rooted in the analysis of spatial organization of epigenetic marks.

Characterizing Typhoon-related Posttraumatic Stress Disorder Based on Multimodal Fusion of Structural, Diffusion, and Functional Magnetic Resonance Imaging.

Diagnosing posttraumatic stress disorder (PTSD) using only single-modality images is controversial. We aimed to use multimodal magnetic resonance imaging (MRI) combining structural, diffusion, and functional MRI to possibly provide a more comprehensive viewpoint on the decisive characteristics of PTSD patients. Typhoon-exposed individuals with (n = 26) and without PTSD (n = 32) and healthy volunteers (n = 30) were enrolled. Five MRI features from three modalities, including two resting-state functional MRI (rs-fMRI) features (amplitude of low-frequency fluctuation, ALFF; and regional homogeneity, ReHo), one structural MRI feature (gray matter density, GM), and two diffusion tensor imaging (DTI) features (fractional anisotropy, FA; and mean diffusivity, MD) were investigated simultaneously with a multimodal canonical correlation analysis + joint independent component analysis model to identify abnormalities in the PTSD brain. We identified statistical differences between PTSD patients and healthy controls in terms of 1 rs-fMRI (ALFF, ReHo) alterations in the superior frontal gyrus, precuneus, inferior parietal lobule (IPL), anterior cingulate cortex (ACC), and posterior cingulate cortex (PCC), 2 DTI (FA, MD) changes in the pons, genu, and splenium of the corpus callosum, and 3 Structural MRI abnormalities in the precuneus, IPL, ACC, and PCC. A novel ReHo component was found to distinguish PTSD and trauma-exposed controls, including the precuneus, IPL, middle frontal gyrus, middle occipital gyrus, and cerebellum. This study reveals that PTSD individuals exhibit intertwined functional and structural anomalies within the default mode network. Some alterations within this network may serve as a potential marker to distinguish between PTSD patients and trauma-exposed controls.

Imaging-based chromatin and epigenetic age, ImAge, quantitates aging and rejuvenation.

Biomarkers of biological age that predict the risk of disease and expected lifespan better than chronological age are key to efficient and cost-effective healthcare1-3. To advance a personalized approach to healthcare, such biomarkers must reliably and accurately capture individual biology, predict biological age, and provide scalable and cost-effective measurements. We developed a novel approach - image-based chromatin and epigenetic age (ImAge) that captures intrinsic progressions of biological age, which readily emerge as principal changes in the spatial organization of chromatin and epigenetic marks in single nuclei without regression on chronological age. ImAge captured the expected acceleration or deceleration of biological age in mice treated with chemotherapy or following a caloric restriction regimen, respectively. ImAge from chronologically identical mice inversely correlated with their locomotor activity (greater activity for younger ImAge), consistent with the widely accepted role of locomotion as an aging biomarker across species. Finally, we demonstrated that ImAge is reduced following transient expression of OSKM cassette in the liver and skeletal muscles and reveals heterogeneity of in vivo reprogramming. We propose that ImAge represents the first-in-class imaging-based biomarker of aging with single-cell resolution.

Active cell divisions generate fourfold orientationally ordered phase in living tissue.

Morphogenesis, the process through which genes generate form, establishes tissue-scale order as a template for constructing the complex shapes of the body plan. The extensive growth required to build these ordered substrates is fuelled by cell proliferation, which, naively, should destroy order. Understanding how active morphogenetic mechanisms couple cellular and mechanical processes to generate order-rather than annihilate it-remains an outstanding question in animal development. We show that cell divisions are the primary drivers of tissue flow, leading to a fourfold orientationally ordered phase. Waves of anisotropic cell proliferation propagate across the embryo with precise patterning. Defects introduced into the nascent lattice by cell divisions are moved out of the tissue bulk towards the boundary by subsequent divisions. Specific cell proliferation rates and orientations enable cell divisions to organize rather than fluidize the tissue. We observe this using live imaging and tissue cartography to analyse the dynamics of fourfold tissue ordering in the trunk segmental ectoderm of the crustacean Parhyale hawaiensis beginning 72 h after egg lay. The result is a robust, active mechanism for generating global orientational order in a non-equilibrium system that sets the stage for the subsequent development of shape and form.