Dataset Information

High-resolution 3D imaging uncovers organ-specific vascular control of tissue aging.

ABSTRACT: Blood vessels provide supportive microenvironments for maintaining tissue functions. Age-associated vascular changes and their relation to tissue aging and pathology are poorly understood. Here, we perform 3D imaging of young and aging vascular beds. Multiple organs in mice and humans demonstrate an age-dependent decline in vessel density and pericyte numbers, while highly remodeling tissues such as skin preserve the vasculature. Vascular attrition precedes the appearance of cellular hallmarks of aging such as senescence. Endothelial VEGFR2 loss-of-function mice demonstrate that vascular perturbations are sufficient to stimulate cellular changes coupled with aging. Age-associated tissue-specific molecular changes in the endothelium drive vascular loss and dictate pericyte to fibroblast differentiation. Lineage tracing of perivascular cells with inducible PDGFR? and NG2 Cre mouse lines demonstrated that increased pericyte to fibroblast differentiation distinguishes injury-induced organ fibrosis and zymosan-induced arthritis. To spur further discoveries, we provide a freely available resource with 3D vascular and tissue maps.

SUBMITTER: Chen J

PROVIDER: S-EPMC7857692 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High-resolution 3D imaging uncovers organ-specific vascular control of tissue aging.

Chen Junyu J Sivan Unnikrishnan U Tan Sin Lih SL Lippo Luciana L De Angelis Jessica J Labella Rossella R Singh Amit A Chatzis Alexandros A Cheuk Stanley S Medhghalchi Mino M Gil Jesus J Hollander Georg G Marsden Brian D BD Williams Richard R Ramasamy Saravana K SK Kusumbe Anjali P AP

Science advances 20210203 6

Blood vessels provide supportive microenvironments for maintaining tissue functions. Age-associated vascular changes and their relation to tissue aging and pathology are poorly understood. Here, we perform 3D imaging of young and aging vascular beds. Multiple organs in mice and humans demonstrate an age-dependent decline in vessel density and pericyte numbers, while highly remodeling tissues such as skin preserve the vasculature. Vascular attrition precedes the appearance of cellular hallmarks o ...[more]

PMID: 33536212

Similar Datasets

Project description:Heart structure and function change with age, and the notion that the heart may age faster for some individuals than for others has driven interest in estimating cardiac age acceleration. However, current approaches have limited feature richness (heart measurements; radiomics) or capture extraneous data and therefore lack cardiac specificity (deep learning [DL] on unmasked chest MRI). These technical limitations have been a barrier to efforts to understand genetic contributions to age acceleration. We hypothesized that a video-based DL model provided with heart-masked MRI data would capture a rich yet cardiac-specific representation of cardiac aging. In 61,691 UK Biobank participants, we excluded noncardiac pixels from cardiac MRI and trained a video-based DL model to predict age from one cardiac cycle in the 4-chamber view. We then computed cardiac age acceleration as the bias-corrected prediction of heart age minus the calendar age. Predicted heart age explained 71.1% of variance in calendar age, with a mean absolute error of 3.3 years. Cardiac age acceleration was linked to unfavorable cardiac geometry and systolic and diastolic dysfunction. We also observed links between cardiac age acceleration and diet, decreased physical activity, increased alcohol and tobacco use, and altered levels of 239 serum proteins, as well as adverse brain MRI characteristics. We found cardiac age acceleration to be heritable (h2g 26.6%); a genome-wide association study identified 8 loci related to linked to cardiomyopathy (near TTN, TNS1, LSM3, PALLD, DSP, PLEC, ANKRD1 and MYO18B) and an additional 16 loci (near MECOM, NPR3, KLHL3, HDGFL1, CDKN1A, ELN, SLC25A37, PI15, AP3M1, HMGA2, ADPRHL1, PGAP3, WNT9B, UHRF1 and DOK5). Of the discovered loci, 21 were not previously associated with cardiac age acceleration. Mendelian randomization revealed that lower genetically mediated levels of 6 circulating proteins (MSRA most strongly), as well as greater levels of 5 proteins (LXN most strongly) were associated with cardiac age acceleration, as were greater blood pressure and Lp(a). A polygenic score for cardiac age acceleration predicted earlier onset of arrhythmia, heart failure, myocardial infarction, and mortality. These findings provide a thematic understanding of cardiac age acceleration and suggest that heart- and vascular-specific factors are key to cardiac age acceleration, predominating over a more global aging program.

Project description:The zebrafish is extensively used as an animal model for human and fish diseases. However, our understanding of the structural organization of its immune system remains incomplete, especially the mucosa-associated lymphoid tissues (MALTs). Teleost MALTs are commonly perceived as diffuse and scattered populations of immune cells throughout the mucosa. Yet, structured MALTs have been recently discovered in Atlantic salmon (Salmo salar L.), including the interbranchial lymphoid tissue (ILT) in the gills. The existence of the ILT was only recently identified in zebrafish and other fish species, highlighting the need for in-depth characterizations of the gill-associated lymphoid tissue (GIALT) in teleosts. Here, using 3-D high-resolution microscopy, we analyze the GIALT of adult zebrafish with an immuno-histology approach that reveals the organization of lymphoid tissues via the labeling of T/NK cells with an antibody directed to a highly conserved epitope on the kinase ZAP70. We show that the GIALT in zebrafish is distributed over at least five distinct sub-regions, an organization found in all pairs of gill arches. The GIALT is diffuse in the pharyngeal part of the gill arch, the interbranchial septum and the filaments/lamellae, and structured in two sub-regions: the ILT, and a newly discovered lymphoid structure located along each side of the gill arch, which we named the Amphibranchial Lymphoid Tissue (ALT). Based on RAG2 expression, neither the ILT nor the ALT constitute additional thymi. The ALT shares several features with the ILT such as presence of abundant lymphoid cells and myeloid cells embedded in a network of reticulated epithelial cells. Further, the ILT and the ALT are also a site for T/NK cell proliferation. Both ILT and ALT show structural changes after infection with Spring Viraemia of Carp Virus (SVCV). Together, these data suggest that ALT and ILT play an active role in immune responses. Comparative studies show that whereas the ILT seems absent in most neoteleosts ("Percomorphs"), the ALT is widely present in cyprinids, salmonids and neoteleosts, suggesting that it constitutes a conserved tissue involved in the protection of teleosts via the gills.

Dataset Information

High-resolution 3D imaging uncovers organ-specific vascular control of tissue aging.

Publications

High-resolution 3D imaging uncovers organ-specific vascular control of tissue aging.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets