Aging is characterized by a gradual loss of function occurring at the molecular, cellular, tissue and organismal levels. At the chromatin level, aging associates with progressive accumulation of epigenetic errors that eventually lead to aberrant gene regulation, stem cell exhaustion, senescence, and deregulated cell/tissue homeostasis. Nuclear reprogramming to pluripotency can revert both the age and the identity of any cell to that of an embryonic cell. Recent evidence shows that transient reprogramming can ameliorate age-associated hallmarks and extend lifespan in progeroid mice. However, it is unknown how this form of rejuvenation would apply to naturally aged human cells. Here we show that transient expression of nuclear reprogramming factors, mediated by expression of mRNAs, promotes a rapid and broad amelioration of cellular aging, including resetting of epigenetic clock, reduction of the inflammatory profile in chondrocytes, and restoration of youthful regenerative response to aged, human muscle stem cells, in each case without abolishing cellular identity.

Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type–specific RNA splicing was discovered and analyzed across tissues within an individual.

The microscopic modeling of surfactant systems is of the utmost importance in understanding the mechanisms related to the micellization process because it allows for prediction and comparison with experimental data of diverse equilibrium system properties. In this work, we present a coarse-grained model for Pluronics, a trademarked type of triblock copolymer, from simulations based on a single-chain mean-field theory (SCMF). This microscopic model is used to quantify the micellization process of these nonionic surfactants at 37 °C and has been shown to be able to quantitatively reproduce experimental data of the critical micelle concentration (CMC) along with other equilibrium properties. In particular, these results correctly capture the experimental behavior with respect to the lengths of the hydrophobic and hydrophilic moieties of the surfactants for low and medium hydrophobicities. However, for the more highly hydrophobic systems with low CMCs, a deviation is found which has been previously attributed to nonequilibrium effects in the experimental data (Garcı́a Daza, F. A.; Mackie, A. D. Low Critical Micelle Concentration Discrepancy between Theory and Experiment. J. Phys. Chem. Lett. 2014, 5, 2027-2032).

Aging is characterized by a gradual loss of function occurring at the molecular, cellular, tissue and organismal levels [1][2][3] . At the chromatin level, aging is associated with the progressive accumulation of epigenetic errors that eventually lead to aberrant gene regulation, stem cell exhaustion, senescence, and deregulated cell/tissue homeostasis 3 . The technology of nuclear reprogramming to pluripotency, through over-expression of a small number of transcription factors, can revert both the age and the identity of any cell to that of an embryonic cell by driving epigenetic reprogramming 2,4,5 . Recent evidence has shown that transient transgenic reprogramming can ameliorate age-associated hallmarks and extend lifespan in progeroid mice 6 .However, it is unknown how this form of 'epigenetic rejuvenation' would apply to physiologically aged cells and, importantly, how it might translate to human cells. Here we show that transient reprogramming, mediated by transient expression of mRNAs, promotes a rapid reversal of both cellular aging and of epigenetic clock in human fibroblasts and endothelial cells, reduces the inflammatory profile in human chondrocytes, and restores youthful regenerative response to aged, human muscle stem cells, in each case without abolishing cellular identity. Our method, that we named Epigenetic Reprogramming of Aging (ERA), paves the way to a novel, potentially translatable strategy for ex vivo cell rejuvenation treatment. In addition, ERA holds promise for in vivo tissue rejuvenation therapies to reverse the physiological manifestations of aging and the risk for the development of age-related diseases.

Microscopic modeling of surfactant systems is expected to be an important tool to describe, understand, and take full advantage of the micellization process for different molecular architectures. Here, we implement a single chain mean field theory to study the relevant equilibrium properties such as the critical micelle concentration (CMC) and aggregation number for three sets of surfactants with different geometries maintaining constant the number of hydrophobic and hydrophilic monomers. The results demonstrate the direct effect of the block organization for the surfactants under study by means of an analysis of the excess energy and entropy which can be accurately determined from the mean-field scheme. Our analysis reveals that the CMC values are sensitive to branching in the hydrophilic head part of the surfactant and can be observed in the entropy-enthalpy balance, while aggregation numbers are also affected by splitting the hydrophobic tail of the surfactant and are manifested by slight changes in the packing entropy.