Furman, D. et al. Chronic inflammation in the etiology of disease across the life span. Nat. Med. 25, 1822–1832 (2019).
Arem, H. et al. Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship. JAMA Intern. Med. 175, 959–967 (2015).
Sanford, J. A. et al. Molecular Transducers of Physical Activity Consortium (MoTrPAC): mapping the dynamic responses to exercise. Cell 181, 1464–1474 (2020).
MoTrPAC Study Group, Lead Analysts & MoTrPAC Study Group Temporal dynamics of the multi-omic response to endurance exercise training. Nature 629, 174–183 (2024).
Langston, P. K. et al. Regulatory T cells shield muscle mitochondria from interferon-γ-mediated damage to promote the beneficial effects of exercise. Sci. Immunol. 8, eadi5377 (2023).
Langston, P. K. & Mathis, D. Immunological regulation of skeletal muscle adaptation to exercise. Cell Metab. 36, 1175–1183 (2024).
Becker, M. et al. Regulatory T cells require IL6 receptor α signaling to control skeletal muscle function and regeneration. Cell Metab. 35, 1736–1751 (2023).
Van der Stede, T. et al. Cellular deconstruction of the human skeletal muscle microenvironment identifies an exercise-induced histaminergic crosstalk. Cell Metab. 37, 842–856 (2025).
Pillon, N. J. et al. Distinctive exercise-induced inflammatory response and exerkine induction in skeletal muscle of people with type 2 diabetes. Sci. Adv. 8, eabo3192 (2022).
Kang, X. et al. Exercise-induced musclin determines the fate of fibro-adipogenic progenitors to control muscle homeostasis. Cell Stem Cell 31, 212–226 (2024).
Wei, W. et al. Organism-wide, cell-type-specific secretome mapping of exercise training in mice. Cell Metab. 35, 1261–1279 (2023).
Knudsen, N. H. et al. Interleukin-13 drives metabolic conditioning of muscle to endurance exercise. Science 368, eaat3987 (2020).
Yang, J. et al. Single-cell dissection of the obesity–exercise axis in adipose–muscle tissues implies a critical role for mesenchymal stem cells. Cell Metab. 34, 1578–1593 (2022).
Liu, L. et al. Exercise reprograms the inflammatory landscape of multiple stem cell compartments during mammalian aging. Cell Stem Cell 30, 689–705 (2023).
Joe, A. W. et al. Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis. Nat. Cell Biol. 12, 153–163 (2010).
Uezumi, A. et al. Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle. Nat. Cell Biol. 12, 143–152 (2010).
Uezumi, A. et al. Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle. J. Cell Sci. 124, 3654–3664 (2011).
Wosczyna, M. N. et al. Mesenchymal stromal cells are required for regeneration and homeostatic maintenance of skeletal muscle. Cell Rep. 27, 2029–2035 (2019).
Yaghi, O. K. et al. A discrete ‘early-responder’ stromal-cell subtype orchestrates immunocyte recruitment to injured tissue. Nat. Immunol. 24, 2053–2067 (2023).
Valero, M. C. et al. Eccentric exercise facilitates mesenchymal stem cell appearance in skeletal muscle. PLoS ONE 7, e29760 (2012).
Saito, Y. et al. Exercise enhances skeletal muscle regeneration by promoting senescence in fibro-adipogenic progenitors. Nat. Commun. 11, 889 (2020).
Chiquet-Ehrismann, R. & Chiquet, M. Tenascins: regulation and putative functions during pathological stress. J. Pathol. 200, 488–499 (2003).
Midwood, K. S., Hussenet, T., Langlois, B. & Orend, G. Advances in tenascin-C biology. Cell. Mol. Life Sci. 68, 3175–3199 (2011).
Midwood, K. et al. Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nat. Med. 15, 774–780 (2009).
Zuliani-Alvarez, L. et al. Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers. Nat. Commun. 8, 1595 (2017).
Marzeda, A. M. & Midwood, K. S. Internal affairs: tenascin-C as a clinically relevant, endogenous driver of innate immunity. J. Histochem. Cytochem. 66, 289–304 (2018).
Lukjanenko, L. et al. Aging disrupts muscle stem cell function by impairing matricellular WISP1 secretion from fibro-adipogenic progenitors. Cell Stem Cell 24, 433–446 (2019).
Pillon, N. J. et al. Transcriptomic profiling of skeletal muscle adaptations to exercise and inactivity. Nat. Commun. 11, 470 (2020).
Furrer, R. et al. Molecular control of endurance training adaptation in male mouse skeletal muscle. Nat. Metab. 5, 2020–2035 (2023).
Timmons, J. A. et al. Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J. Appl. Physiol. 108, 1487–1496 (2010).
Vaynman, S., Ying, Z. & Gomez-Pinilla, F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur. J. Neurosci. 20, 2580–2590 (2004).
Szuhany, K. L., Bugatti, M. & Otto, M. W. A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. J. Psychiatr. Res. 60, 56–64 (2015).
Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).
Flück, M., Tunc-Civelek, V. & Chiquet, M. Rapid and reciprocal regulation of tenascin-C and tenascin-Y expression by loading of skeletal muscle. J. Cell Sci. 113, 3583–3591 (2000).
Chiquet, M., Renedo, A. S., Huber, F. & Fluck, M. How do fibroblasts translate mechanical signals into changes in extracellular matrix production?. Matrix Biol. 22, 73–80 (2003).
Tse, J.R. & Engler, A.J. Preparation of hydrogel substrates with tunable mechanical properties. Curr. Protoc. Cell Biol. Chapter 10, Unit 10.16 (2010).
Meizlish, M. L. et al. Mechanosensing regulates tissue repair program in macrophages. Sci. Adv. 10, eadk6906 (2024).
Du, H. et al. Tuning immunity through tissue mechanotransduction. Nat. Rev. Immunol. 23, 174–188 (2023).
Li, X. et al. Stimulation of Piezo1 by mechanical signals promotes bone anabolism. eLife 8, e49631 (2019).
Zhou, T. et al. Piezo1/2 mediate mechanotransduction essential for bone formation through concerted activation of NFAT–YAP1–β-catenin. eLife 9, e52779 (2020).
Shen, B. et al. A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis. Nature 591, 438–444 (2021).
Suchyna, T. M. et al. Identification of a peptide toxin from Grammostola spatulata spider venom that blocks cation-selective stretch-activated channels. J. Gen. Physiol. 115, 583–598 (2000).
Bae, C., Sachs, F. & Gottlieb, P. A. The mechanosensitive ion channel Piezo1 is inhibited by the peptide GsMTx4. Biochemistry 50, 6295–6300 (2011).
Syeda, R. et al. Chemical activation of the mechanotransduction channel Piezo1. eLife 4, e07369 (2015).
Blythe, N. M. et al. Mechanically activated Piezo1 channels of cardiac fibroblasts stimulate p38 mitogen-activated protein kinase activity and interleukin-6 secretion. J. Biol. Chem. 294, 17395–17408 (2019).
Whitmarsh, A. J. & Davis, R. J. Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J. Mol. Med. 74, 589–607 (1996).
Winzen, R. et al. The p38 MAP kinase pathway signals for cytokine-induced mRNA stabilization via MAP kinase-activated protein kinase 2 and an AU-rich region-targeted mechanism. EMBO J. 18, 4969–4980 (1999).
Chiquet, M. Regulation of extracellular matrix gene expression by mechanical stress. Matrix Biol. 18, 417–426 (1999).
Kjaer, M. Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol. Rev. 84, 649–698 (2004).
Hanna, B. S. et al. The gut microbiota promotes distal tissue regeneration via RORγ+ regulatory T cell emissaries. Immunity 56, 829–846 (2023).
Tidball, J. G. Regulation of muscle growth and regeneration by the immune system. Nat. Rev. Immunol. 17, 165–178 (2017).
Alnaqeeb, M. A., Al Zaid, N. S. & Goldspink, G. Connective tissue changes and physical properties of developing and ageing skeletal muscle. J. Anat. 139, 677–689 (1984).
Wood, L. K. et al. Intrinsic stiffness of extracellular matrix increases with age in skeletal muscles of mice. J Appl. Physiol. 117, 363–369 (2014).
Stearns-Reider, K. M. et al. Aging of the skeletal muscle extracellular matrix drives a stem cell fibrogenic conversion. Aging Cell 16, 518–528 (2017).
Wang, Y., Wehling-Henricks, M., Samengo, G. & Tidball, J. G. Increases of M2a macrophages and fibrosis in aging muscle are influenced by bone marrow aging and negatively regulated by muscle-derived nitric oxide. Aging Cell 14, 678–688 (2015).
Wang, Y. et al. Myeloid cell-specific mutation of Spi1 selectively reduces M2-biased macrophage numbers in skeletal muscle, reduces age-related muscle fibrosis and prevents sarcopenia. Aging Cell 21, e13690 (2022).
Abbott, C. B. et al. A novel stable isotope approach demonstrates surprising degree of age-related decline in skeletal muscle collagen proteostasis. Function 2, zqab028 (2021).
Rode, B. et al. Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance. Nat. Commun. 8, 350 (2017).
Xie, Z. et al. Enteric neuronal Piezo1 maintains mechanical and immunological homeostasis by sensing force. Cell 188, 2417–2432 (2025).
Solis, A. G. et al. Mechanosensation of cyclical force by Piezo1 is essential for innate immunity. Nature 573, 69–74 (2019).
Atcha, H. et al. Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing. Nat. Commun. 12, 3256 (2021).
Chakraborty, M. et al. Mechanical stiffness controls dendritic cell metabolism and function. Cell Rep. 34, 108609 (2021).
Coste, B. et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330, 55–60 (2010).
Huang, G., Shi, L. Z. & Chi, H. Regulation of JNK and p38 MAPK in the immune system: signal integration, propagation and termination. Cytokine 48, 161–169 (2009).
Denton, R. M. Regulation of mitochondrial dehydrogenases by calcium ions. Biochim. Biophys. Acta 1787, 1309–1316 (2009).
Langston, P. K. et al. Glycerol phosphate shuttle enzyme GPD2 regulates macrophage inflammatory responses. Nat. Immunol. 20, 1186–1195 (2019).
Medzhitov, R. The spectrum of inflammatory responses. Science 374, 1070–1075 (2021).
Silver, J. S. et al. Injury-mediated stiffening persistently activates muscle stem cells through YAP and TAZ mechanotransduction. Sci. Adv. 7, eabe4501 (2021).
Gosselin, L. E. et al. Effect of exercise training on passive stiffness in locomotor skeletal muscle: role of extracellular matrix. J. Appl. Physiol. 85, 1011–1016 (1998).
Kuswanto, W. et al. Poor repair of skeletal muscle in aging mice reflects a defect in local, interleukin-33-dependent accumulation of regulatory T cells. Immunity 44, 355–367 (2016).
Moiseeva, V. et al. Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration. Nature 613, 169–178 (2023).
Lovric, A. et al. Single-cell sequencing deconvolutes cellular responses to exercise in human skeletal muscle. Commun. Biol. 5, 1121 (2022).
Cahalan, S. M. et al. Piezo1 links mechanical forces to red blood cell volume. eLife 4, e07370 (2015).
Handschin, C. et al. Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1α muscle-specific knock-out animals. J. Biol. Chem. 282, 30014–30021 (2007).
Liu, L., Cheung, T. H., Charville, G. W. & Rando, T. A. Isolation of skeletal muscle stem cells by fluorescence-activated cell sorting. Nat. Protoc. 10, 1612–1624 (2015).
Langston, P. K. et al. Au-ACRAMTU-PEt3 alters redox balance to inhibit T cell proliferation and function. J. Immunol. 195, 1984–1994 (2015).
Picelli, S. et al. Full-length RNA-seq from single cells using Smart-seq2. Nat. Protoc. 9, 171–181 (2014).
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
Zhu, A., Ibrahim, J. G. & Love, M. I. Heavy-tailed prior distributions for sequence count data: removing the noise and preserving large differences. Bioinformatics 35, 2084–2092 (2019).
Korotkevich, G. et al. Fast gene set enrichment analysis. Preprint at bioRxiv https://doi.org/10.1101/060012 (2021).
Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1523 (2019).
Calò, A. et al. Spatial mapping of the collagen distribution in human and mouse tissues by force volume atomic force microscopy. Sci. Rep. 10, 15664 (2020).
Acerbi, I. et al. Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration. Integr. Biol. 7, 1120–1134 (2015).
Peloquin, J., Huynh, J., Williams, R. M. & Reinhart-King, C. A. Indentation measurements of the subendothelial matrix in bovine carotid arteries. J. Biomech. 44, 815–821 (2011).
Shen, Y., Schmidt, T. & Diz-Munoz, A. Protocol on tissue preparation and measurement of tumor stiffness in primary and metastatic colorectal cancer samples with an atomic force microscope. STAR Protoc. 1, 100167 (2020).
Sato, S. et al. Time of exercise specifies the impact on muscle metabolic pathways and systemic energy homeostasis. Cell Metab. 30, 92–110 (2019).


















Leave a Reply