Year: 2026
Type: article
Abstract: Age-associated hematopoietic skewing results in an increase in the neutrophil-to-lymphocyte ratio, which serves as a strong predictor of all-cause mortality in older adults, although its causes are incompletely understood. Here we show that cytotoxic CD4 + T lymphocytes accumulate in the bone marrow of mice during aging and induce myelopoiesis, increasing the neutrophil-to-lymphocyte ratio. T cell receptor-dependent induction of mitochondrial stress and activation of STING upregulates the chemokine CCL5 in CD4 + T lymphocytes. During aging, hematopoietic stem cells and downstream myeloid progenitors upregulate CCR5, the primary receptor for CCL5. Genetic ablation of Ccr5 in hematopoietic progenitors mitigates T cell-induced myeloid skewing and neutrophil expansion. Pharmacological blockade of CCR5 using the Food and Drug Administration-approved drug maraviroc normalizes myelopoiesis, reduces circulating and tissue-infiltrating neutrophils, and improves multiple aging-related biomarkers and functional outcomes in aged mice. Together, these findings demonstrate a T cell–bone marrow axis that exacerbates age-associated decline and highlight CCR5 inhibition as a potential geroprotective strategy.
Source: Nature Aging
Authors: Enrique Gabandé-Rodríguez, Gonzalo Soto-Heredero, Elisa Carrasco, Carlos Anerillas, José Ignacio Escrig-Larena, Jorge Martínez-Cano, Sandra Delgado-Pulido, Isaac Francos-Quijorna, Gabriela Desdín-Micó, Tatiana Smirnova, Manuel M. Gómez de las Heras, Álvaro Fernández-Almeida, Alice Leandri, Andrea Cugurra, Eva María Blanco, Elia Winand-Osete, Pablo Ramírez-Ruiz de Erenchun, Virginia Zorita, Camilla Bean, Valentin Basset, Françoise Solly, Amanda Garrido, Rafael de Cabo, Santos Mañes, Manolis Pasparakis, Matteo Iannacone, César Cobaleda, Olaia Naveiras, Myriam Gorospe, María Mittelbrunn
Institutions: Consejo Superior de Investigaciones Científicas, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Instituto Ramón y Cajal de Investigación Sanitaria, National Institute on Aging, Centre Hospitalier Universitaire Vaudois, University of Lausanne, University of Padua, Spanish National Centre for Cardiovascular Research, Veneto Institute of Molecular Medicine, Saint Camillus International University of Health and Medical Sciences, Centro Nacional de Biotecnología, University of Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: National Science Foundation, Comunidad de Madrid, Ministerio de Ciencia, Innovación y Universidades, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Universidad Autónoma de Madrid, Ministerio de Ciencia e Innovación, National Institutes of Health, Agencia Estatal de Investigación, National Institute on Aging
Awards: G1105844351, G1175115578, G1272900390, G131395453, G1389939605, G1401168639, G1610934229, G1855990336, G2262748287, G2309174360, G252646220, G2660406951, G278662286, G294895050, G300979063, G3059641936, G3371592566, G3449904603, G3480869486, G3518538256, G3722519122, G395944757, Rejuvenating hematopoietic stem cells through partial in vivo reprogramming for improved functionality in aging and bone marrow failure syndromes, G4212894969, G425668148, G430777504, G4620043560, G464105488, G491712853, G504565433, G5080475149, G5421974903, G5483478483, G5635532810, G5879405622, G593054264, G6083578192, G691503953, G7084143925, G7190536026, G7395345766, G7434936867, G745419941, G7780475403, G7805626310, G7863371703, G7949600678, G7995181139, G8345352404, G8497050386, G8575141037, G8626970783, G8667377315, G8920660035, G99296377
OpenAlex ID: W7204259855