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Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.

Motile cells navigate through tissue by relying on tactile cues from gradients provided by extracellular matrix such as ligand density or stiffness. Mesenchymal stem cells (MSCs) and fibroblasts encounter adhesive or ‘haptotactic’ gradients at the interface between healthy and fibrotic tissue as they migrate towards an injury site. Mimicking this phenomenon, we developed tunable RGD and collagen gradients in polyacrylamide hydrogels of physiologically relevant stiffness using density gradient multilayer polymerization to better understand how such ligand gradients regulate migratory behaviors. Independent of ligand composition and fiber deformation, haptotaxis was observed in mouse 3T3 fibroblasts. Human MSCs however, haptotaxed only when cell-substrate adhesion was indirectly reduced via addition of free soluble matrix ligand mimetic peptides. Under basal conditions, MSCs were more contractile than fibroblasts. However, the presence of soluble adhesive peptides reduced MSC-induced substrate deformations; increased contractility may contribute to limited migration, but modulating cytoskeletal assembly was ineffective at promoting MSC haptotaxis. When introduced to gradients of increased absolute ligand concentrations, 3T3s displayed increased contractility and no longer haptotaxed. These data suggest that haptotactic behaviors are limited by adhesion and that although both cell types may home to tissue to aid in repair, fibroblasts may be more responsive to ligand gradients than MSCs.

© 2015 Biomedical Engineering Society Motile cells navigate through tissue by relying on tactile cues from gradients provided by extracellular matrix such as ligand density or stiffness. Mesenchymal stem cells (MSCs) and fibroblasts encounter adhesive or ‘haptotactic’ gradients at the interface between healthy and fibrotic tissue as they migrate towards an injury site. Mimicking this phenomenon, we developed tunable RGD and collagen gradients in polyacrylamide hydrogels of physiologically relevant stiffness using density gradient multilayer polymerization to better understand how such ligand gradients regulate migratory behaviors. Independent of ligand composition and fiber deformation, haptotaxis was observed in mouse 3T3 fibroblasts. Human MSCs however, haptotaxed only when cell-substrate adhesion was indirectly reduced via addition of free soluble matrix ligand mimetic peptides. Under basal conditions, MSCs were more contractile than fibroblasts. However, the presence of soluble adhesive peptides reduced MSC-induced substrate deformations; increased contractility may contribute to limited migration, but modulating cytoskeletal assembly was ineffective at promoting MSC haptotaxis. When introduced to gradients of increased absolute ligand concentrations, 3T3s displayed increased contractility and no longer haptotaxed. These data suggest that haptotactic behaviors are limited by adhesion and that although both cell types may home to tissue to aid in repair, fibroblasts may be more responsive to ligand gradients than MSCs.

Motile cells navigate through tissue by relying on tactile cues from gradients provided by extracellular matrix such as ligand density or stiffness. Mesenchymal stem cells (MSCs) and fibroblasts encounter adhesive or ‘haptotactic’ gradients at the interface between healthy and fibrotic tissue as they migrate towards an injury site. Mimicking this phenomenon, we developed tunable RGD and collagen gradients in polyacrylamide hydrogels of physiologically relevant stiffness using density gradient multilayer polymerization to better understand how such ligand gradients regulate migratory behaviors. Independent of ligand composition and fiber deformation, haptotaxis was observed in mouse 3T3 fibroblasts. Human MSCs however, haptotaxed only when cell-substrate adhesion was indirectly reduced via addition of free soluble matrix ligand mimetic peptides. Under basal conditions, MSCs were more contractile than fibroblasts. However, the presence of soluble adhesive peptides reduced MSC-induced substrate deformations; increased contractility may contribute to limited migration, but modulating cytoskeletal assembly was ineffective at promoting MSC haptotaxis. When introduced to gradients of increased absolute ligand concentrations, 3T3s displayed increased contractility and no longer haptotaxed. These data suggest that haptotactic behaviors are limited by adhesion and that although both cell types may home to tissue to aid in repair, fibroblasts may be more responsive to ligand gradients than MSCs.

Graphite nanoplatelets (GNPs) are an attractive class of reinforcement materials as they offer both high modulus and high strength. GNPs have a thickness of less than 100 nm although their planar dimensions can be as large as a few micrometers. As with any other nanoscale particles, their effectiveness as a reinforcement phase depends on the surface functionalization, which controls dispersion and interfacial bonding. A simple surface oxidation using nitric acid is shown to yield as good an improvement in composite properties as a few other functional groups chemically bonded to the surface do. The properties discussed include modulus, strength, fracture toughness, adhesive strength, thermal and electrical conductivities, and dielectric constants. Methods of further exfoliating graphite nanoplatelets are discussed together with the associated benefits on composite properties. Potential applications of graphite nanoplatelet composites are presented to conclude the report.

Heat transport in polymer nanocomposites reinforced with graphite nanoplatelets (GNPs) is studied using high-precision thermal conductivity measurements. The resistance to heat conduction across interfaces between GNPs and the polymer matrix has a strong effect on energy transport in the nanocomposites. The thermal conductivity is observed to increase when GNPs are pretreated with nitric acid to improve interfacial bonding. The improvement in the thermal conductivity, however, is much smaller than the corresponding improvement in mechanical properties. The thermal interface resistance extracted from the present thermal conductivity data is comparable to that obtained from the previously reported data on carbon nanotube suspensions. (c)2006 American Institute of Physics.

Heat transport in polymer nanocomposites reinforced with graphite nanoplatelets (GNPs) is studied using high-precision thermal conductivity measurements. The resistance to heat conduction across interfaces between GNPs and the polymer matrix has a strong effect on energy transport in the nanocomposites. The thermal conductivity is observed to increase when GNPs are pretreated with nitric acid to improve interfacial bonding. The improvement in the thermal conductivity, however, is much smaller than the corresponding improvement in mechanical properties. The thermal interface resistance extracted from the present thermal conductivity data is comparable to that obtained from the previously reported data on carbon nanotube suspensions. (c)2006 American Institute of Physics.