{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:48:08Z","timestamp":1793692088492,"version":"4.5.1"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat. Nanotechnol."],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1038\/s41565-025-01972-7","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T09:04:28Z","timestamp":1755594268000},"page":"1332-1344","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["An energy metabolism-engaged nanomedicine maintains mitochondrial homeostasis to alleviate cellular ageing"],"prefix":"10.1038","volume":"20","author":[{"given":"Liyuan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijie","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0671-6822","authenticated-orcid":false,"given":"Nan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0495-4720","authenticated-orcid":false,"given":"Xiaoshuai","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengren","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danqing","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengye","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangbo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmeng","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanghui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4657-6131","authenticated-orcid":false,"given":"Dan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3885-5149","authenticated-orcid":false,"given":"Cunyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8193-6729","authenticated-orcid":false,"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"1972_CR1","doi-asserted-by":"publisher","first-page":"eaao6806","DOI":"10.1126\/scitranslmed.aao6806","volume":"10","author":"AK Picke","year":"2018","unstructured":"Picke, A. K. et al. Thy-1 (CD90) promotes bone formation and protects against obesity. Sci. Transl. Med. 10, eaao6806 (2018).","journal-title":"Sci. Transl. Med."},{"key":"1972_CR2","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1126\/science.284.5411.143","volume":"284","author":"MF Pittenger","year":"1999","unstructured":"Pittenger, M. F. et al. Multilineage potential of adult human mesenchymal stem cells. Science 284, 143\u2013147 (1999).","journal-title":"Science"},{"key":"1972_CR3","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39958-5","volume":"14","author":"Y Gao","year":"2023","unstructured":"Gao, Y. et al. Multi-omics analysis of human mesenchymal stem cells shows cell aging that alters immunomodulatory activity through the downregulation of PD-L1. Nat. Commun. 14, 4373 (2023).","journal-title":"Nat. Commun."},{"key":"1972_CR4","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1038\/s41591-018-0030-x","volume":"24","author":"M Maryanovich","year":"2018","unstructured":"Maryanovich, M. et al. Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche. Nat. Med. 24, 782\u2013791 (2018).","journal-title":"Nat. Med."},{"key":"1972_CR5","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/s41586-021-03795-7","volume":"597","author":"TH Ambrosi","year":"2021","unstructured":"Ambrosi, T. H. et al. Aged skeletal stem cells generate an inflammatory degenerative niche. Nature 597, 256\u2013262 (2021).","journal-title":"Nature"},{"key":"1972_CR6","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/s41556-018-0124-1","volume":"20","author":"JB Spinelli","year":"2018","unstructured":"Spinelli, J. B. & Haigis, M. C. The multifaceted contributions of mitochondria to cellular metabolism. Nat. Cell Biol. 20, 745\u2013754 (2018).","journal-title":"Nat. Cell Biol."},{"key":"1972_CR7","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/nrm.2017.110","volume":"19","author":"T Shpilka","year":"2018","unstructured":"Shpilka, T. & Haynes, C. M. The mitochondrial UPR: mechanisms, physiological functions and implications in ageing. Nat. Rev. Mol. Cell Biol. 19, 109\u2013120 (2018).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1972_CR8","doi-asserted-by":"publisher","first-page":"e45432","DOI":"10.15252\/embr.201745432","volume":"19","author":"P Lisowski","year":"2018","unstructured":"Lisowski, P., Kannan, P., Mlody, B. & Prigione, A. Mitochondria and the dynamic control of stem cell homeostasis. EMBO Rep. 19, e45432 (2018).","journal-title":"EMBO Rep."},{"key":"1972_CR9","doi-asserted-by":"publisher","first-page":"e158447","DOI":"10.1172\/JCI158447","volume":"132","author":"S Miwa","year":"2022","unstructured":"Miwa, S., Kashyap, S., Chini, E. & von Zglinicki, T. Mitochondrial dysfunction in cell senescence and aging. J. Clin. Invest. 132, e158447 (2022).","journal-title":"J. Clin. Invest."},{"key":"1972_CR10","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nature13264","volume":"510","author":"RM Chin","year":"2014","unstructured":"Chin, R. M. et al. The metabolite alpha-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR. Nature 510, 397\u2013401 (2014).","journal-title":"Nature"},{"key":"1972_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19360-1","volume":"11","author":"Y Wang","year":"2020","unstructured":"Wang, Y. et al. Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations. Nat. Commun. 11, 5596 (2020).","journal-title":"Nat. Commun."},{"key":"1972_CR12","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1016\/j.cmet.2014.06.014","volume":"20","author":"CS Zhang","year":"2014","unstructured":"Zhang, C. S. et al. The lysosomal v-ATPase-Ragulator complex is a common activator for AMPK and mTORC1, acting as a switch between catabolism and anabolism. Cell Metab. 20, 526\u2013540 (2014).","journal-title":"Cell Metab."},{"key":"1972_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43672-7","volume":"14","author":"C Thomas","year":"2023","unstructured":"Thomas, C. et al. A naturally occurring polyacetylene isolated from carrots promotes health and delays signatures of aging. Nat. Commun. 14, 8142 (2023).","journal-title":"Nat. Commun."},{"key":"1972_CR14","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.cmet.2015.06.009","volume":"22","author":"X Fu","year":"2015","unstructured":"Fu, X. et al. 2-Hydroxyglutarate inhibits ATP synthase and mTOR signaling. Cell Metab. 22, 508\u2013515 (2015).","journal-title":"Cell Metab."},{"key":"1972_CR15","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1016\/j.devcel.2024.04.020","volume":"59","author":"G Kelly","year":"2024","unstructured":"Kelly, G. et al. Suppressed basal mitophagy drives cellular aging phenotypes that can be reversed by a p62-targeting small molecule. Dev. Cell 59, 1924\u20131939.e1927 (2024).","journal-title":"Dev. Cell"},{"key":"1972_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08590-2","author":"T Yamada","year":"2025","unstructured":"Yamada, T. et al. Dual regulation of mitochondrial fusion by Parkin-PINK1 and OMA1. Nature https:\/\/doi.org\/10.1038\/s41586-025-08590-2 (2025).","journal-title":"Nature"},{"key":"1972_CR17","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1016\/j.stem.2022.09.002","volume":"29","author":"X Hong","year":"2022","unstructured":"Hong, X. et al. Mitochondrial dynamics maintain muscle stem cell regenerative competence throughout adult life by regulating metabolism and mitophagy. Cell Stem Cell 29, 1506\u20131508 (2022).","journal-title":"Cell Stem Cell"},{"key":"1972_CR18","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/s41593-018-0332-9","volume":"22","author":"EF Fang","year":"2019","unstructured":"Fang, E. F. et al. Mitophagy inhibits amyloid-beta and tau pathology and reverses cognitive deficits in models of Alzheimer\u2019s disease. Nat. Neurosci. 22, 401\u2013412 (2019).","journal-title":"Nat. Neurosci."},{"key":"1972_CR19","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1146\/annurev-biochem-013118-110903","volume":"88","author":"W Kuhlbrandt","year":"2019","unstructured":"Kuhlbrandt, W. Structure and mechanisms of F-type ATP synthases. Annu. Rev. Biochem. 88, 515\u2013549 (2019).","journal-title":"Annu. Rev. Biochem."},{"key":"1972_CR20","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1016\/j.molcel.2023.04.029","volume":"83","author":"Y Lai","year":"2023","unstructured":"Lai, Y. et al. Structure of the human ATP synthase. Mol. Cell 83, 2137\u20132147.e2134 (2023).","journal-title":"Mol. Cell"},{"key":"1972_CR21","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1146\/annurev.biochem.78.081307.104803","volume":"78","author":"C von Ballmoos","year":"2009","unstructured":"von Ballmoos, C., Wiedenmann, A. & Dimroth, P. Essentials for ATP synthesis by F1F0 ATP synthases. Annu. Rev. Biochem. 78, 649\u2013672 (2009).","journal-title":"Annu. Rev. Biochem."},{"key":"1972_CR22","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/s41565-021-00860-0","volume":"16","author":"KA Dawson","year":"2021","unstructured":"Dawson, K. A. & Yan, Y. Current understanding of biological identity at the nanoscale and future prospects. Nat. Nanotechnol. 16, 229\u2013242 (2021).","journal-title":"Nat. Nanotechnol."},{"key":"1972_CR23","doi-asserted-by":"publisher","first-page":"3653","DOI":"10.1002\/anie.201409400","volume":"54","author":"X Zhang","year":"2015","unstructured":"Zhang, X. et al. Black phosphorus quantum dots. Angew. Chem. Int. Ed. 54, 3653\u20133657 (2015).","journal-title":"Angew. Chem. Int. Ed."},{"key":"1972_CR24","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201702815","volume":"14","author":"T Guo","year":"2018","unstructured":"Guo, T. et al. Black phosphorus quantum dots with renal clearance property for efficient photodynamic therapy. Small 14, 1702815 (2018).","journal-title":"Small"},{"key":"1972_CR25","doi-asserted-by":"publisher","first-page":"3596","DOI":"10.1021\/acsnano.5b01143","volume":"9","author":"J Kang","year":"2015","unstructured":"Kang, J. et al. Solvent exfoliation of electronic-grade, two-dimensional black phosphorus. ACS Nano 9, 3596\u20133604 (2015).","journal-title":"ACS Nano"},{"key":"1972_CR26","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201800510","volume":"5","author":"X Zeng","year":"2018","unstructured":"Zeng, X. et al. Polydopamine-modified black phosphorous nanocapsule with enhanced stability and photothermal performance for tumor multimodal treatments. Adv. Sci. 5, 1800510 (2018).","journal-title":"Adv. Sci."},{"key":"1972_CR27","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201603276","volume":"29","author":"W Tao","year":"2017","unstructured":"Tao, W. et al. Black phosphorus nanosheets as a robust delivery platform for cancer theranostics. Adv. Mater. 29, 1603276 (2017).","journal-title":"Adv. Mater."},{"key":"1972_CR28","doi-asserted-by":"publisher","first-page":"6358","DOI":"10.1016\/j.cell.2024.08.021","volume":"187","author":"Y Yang","year":"2024","unstructured":"Yang, Y. et al. Metformin decelerates aging clock in male monkeys. Cell 187, 6358\u20136378.e6329 (2024).","journal-title":"Cell"},{"key":"1972_CR29","first-page":"497","volume":"14","author":"Y Jing","year":"2023","unstructured":"Jing, Y. et al. Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging. Protein Cell 14, 497\u2013512 (2023).","journal-title":"Protein Cell"},{"key":"1972_CR30","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/s41586-023-06783-1","volume":"624","author":"S Sun","year":"2023","unstructured":"Sun, S. et al. CHIT1-positive microglia drive motor neuron ageing in the primate spinal cord. Nature 624, 611\u2013620 (2023).","journal-title":"Nature"},{"key":"1972_CR31","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1126\/science.1160809","volume":"324","author":"MG Vander Heiden","year":"2009","unstructured":"Vander Heiden, M. G., Cantley, L. C. & Thompson, C. B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029\u20131033 (2009).","journal-title":"Science"},{"key":"1972_CR32","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.172","volume":"10","author":"T Ou","year":"2020","unstructured":"Ou, T. et al. SIRT5 deficiency enhances the proliferative and therapeutic capacities of adipose-derived mesenchymal stem cells via metabolic switching. Clin. Transl. Med. 10, e172 (2020).","journal-title":"Clin. Transl. Med."},{"key":"1972_CR33","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/j.stem.2021.01.010","volume":"28","author":"P Deng","year":"2021","unstructured":"Deng, P. et al. Loss of KDM4B exacerbates bone-fat imbalance and mesenchymal stromal cell exhaustion in skeletal aging. Cell Stem Cell 28, 1057\u20131073.e1057 (2021).","journal-title":"Cell Stem Cell"},{"key":"1972_CR34","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/s41368-022-00175-3","volume":"14","author":"P Deng","year":"2022","unstructured":"Deng, P. et al. Loss of KDM4B impairs osteogenic differentiation of OMSCs and promotes oral bone aging. Int. J. Oral Sci. 14, 24 (2022).","journal-title":"Int. J. Oral Sci."},{"key":"1972_CR35","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1038\/s41565-021-00924-1","volume":"16","author":"KE Wheeler","year":"2021","unstructured":"Wheeler, K. E. et al. Environmental dimensions of the protein corona. Nat. Nanotechnol. 16, 617\u2013629 (2021).","journal-title":"Nat. Nanotechnol."},{"key":"1972_CR36","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1001\/jama.1989.03420070075034","volume":"261","author":"NM Resnick","year":"1989","unstructured":"Resnick, N. M. & Greenspan, S. L. \u2018Senile\u2019 osteoporosis reconsidered. JAMA 261, 1025\u20131029 (1989).","journal-title":"JAMA"},{"key":"1972_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29191-x","volume":"13","author":"ZX Wang","year":"2022","unstructured":"Wang, Z. X. et al. Aged bone matrix-derived extracellular vesicles as a messenger for calcification paradox. Nat. Commun. 13, 1453 (2022).","journal-title":"Nat. Commun."},{"key":"1972_CR38","doi-asserted-by":"publisher","first-page":"2122","DOI":"10.1016\/j.stem.2021.08.010","volume":"28","author":"HS Shu","year":"2021","unstructured":"Shu, H. S. et al. Tracing the skeletal progenitor transition during postnatal bone formation. Cell Stem Cell 28, 2122\u20132136.e2123 (2021).","journal-title":"Cell Stem Cell"},{"key":"1972_CR39","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1038\/s12276-023-00950-0","volume":"55","author":"N Thi Nguyen","year":"2023","unstructured":"Thi Nguyen, N. et al. Inhibition of mitochondrial phosphate carrier prevents high phosphate-induced superoxide generation and vascular calcification. Exp. Mol. Med. 55, 532\u2013540 (2023).","journal-title":"Exp. Mol. Med."},{"key":"1972_CR40","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1038\/s41565-021-00952-x","volume":"16","author":"X Shao","year":"2021","unstructured":"Shao, X. et al. Intrinsic bioactivity of black phosphorus nanomaterials on mitotic centrosome destabilization through suppression of PLK1 kinase. Nat. Nanotechnol. 16, 1150\u20131160 (2021).","journal-title":"Nat. Nanotechnol."},{"key":"1972_CR41","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42598-4","volume":"14","author":"Z Li","year":"2023","unstructured":"Li, Z. et al. Self-promoted electroactive biomimetic mineralized scaffolds for bacteria-infected bone regeneration. Nat. Commun. 14, 6963 (2023).","journal-title":"Nat. Commun."},{"key":"1972_CR42","doi-asserted-by":"publisher","first-page":"1806445","DOI":"10.1002\/adfm.201806445","volume":"29","author":"Y Liu","year":"2019","unstructured":"Liu, Y. et al. Thermodynamically controlled self-assembly of hierarchically staggered architecture as an osteoinductive alternative to bone autografts. Adv. Funct. Mater. 29, 1806445 (2019).","journal-title":"Adv. Funct. Mater."}],"container-title":["Nature Nanotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41565-025-01972-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41565-025-01972-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41565-025-01972-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T20:02:19Z","timestamp":1758139339000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41565-025-01972-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,19]]},"references-count":42,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["1972"],"URL":"https:\/\/doi.org\/10.1038\/s41565-025-01972-7","relation":{},"ISSN":["1748-3387","1748-3395"],"issn-type":[{"value":"1748-3387","type":"print"},{"value":"1748-3395","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,19]]},"assertion":[{"value":"26 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}