{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:23:10Z","timestamp":1785435790421,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271590"],"award-info":[{"award-number":["82271590"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82230047"],"award-info":[{"award-number":["82230047"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82271590"],"award-info":[{"award-number":["82271590"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82230047"],"award-info":[{"award-number":["82230047"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2021YFA1100103"],"award-info":[{"award-number":["2021YFA1100103"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"innovation team project of universities in Guangdong province","award":["2023KCXTD004"],"award-info":[{"award-number":["2023KCXTD004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Chronic inflammation accelerates the aging process, and targeted clearance of senescent cells shows potential in alleviating age-related decline. PCC1, a potent senescent cell clearance agent in grape seed extract (GSE), has limited applications due to its low oral bioavailability. This study introduced a novel GSE formulation, Natural Senolytics PCC1 (NSPCC1), which significantly enhanced PCC1 absorption and metabolic characteristics. Validation in two mouse aging models demonstrated that oral administration of NSPCC1 markedly extended lifespan and promoted healthy aging. The formulation improved the capacity for hematopoietic stem\/progenitor cell differentiation and reduced age-related myeloid cell bias. Comprehensive histological analysis revealed attenuated aging phenotypes in bone marrow and skin, improved peripheral blood erythroid parameters, and a partial increase in blood antioxidant capacity, alongside reduced M1 macrophage infiltration and fibrosis in liver, kidney, and lung tissues. These effects were validated through histological assessments, including H&amp;E, Masson, F4\/80, and iNOS staining. This study highlighted the pivotal role of hematopoietic stem cells in aging and established NSPCC1 as a promising natural intervention for age-related pathologies. Its enhanced efficacy lays the groundwork for deeper exploration of natural products in aging biology and provides crucial support for the development of safe and effective anti-aging therapies.<\/jats:p>","DOI":"10.3390\/biology15120922","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:49:42Z","timestamp":1781743782000},"page":"922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hematopoietic Rejuvenation via Natural Senolytic NSPCC1 Delays Inflammatory Aging"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2701-0522","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"},{"name":"Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenglong","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"},{"name":"Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongjinlei","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"},{"name":"Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufang","family":"Wang","sequence":"additional","affiliation":[{"name":"BYHEALTH Institute of Nutrition & Health, Guangzhou 510663, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"BYHEALTH Institute of Nutrition & Health, Guangzhou 510663, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"},{"name":"Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Ju","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"},{"name":"Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2292-8884","authenticated-orcid":false,"given":"Ruikun","family":"He","sequence":"additional","affiliation":[{"name":"BYHEALTH Institute of Nutrition & Health, Guangzhou 510663, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1850-519X","authenticated-orcid":false,"given":"Yuanlong","family":"Ge","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"},{"name":"Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102765","DOI":"10.1016\/j.redox.2023.102765","article-title":"EETs alleviate alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress through the Trim25\/Keap1\/Nrf2 axis","volume":"63","author":"Zhang","year":"2023","journal-title":"Redox Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a041197","DOI":"10.1101\/cshperspect.a041197","article-title":"Aging and Inflammation","volume":"14","author":"Singh","year":"2024","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41569-018-0064-2","article-title":"Inflammageing: Chronic inflammation in ageing, cardiovascular disease, and frailty","volume":"15","author":"Ferrucci","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12979-023-00352-w","article-title":"Aging and chronic inflammation: Highlights from a multidisciplinary wo rkshop","volume":"20","author":"Saavedra","year":"2023","journal-title":"Immun. Ageing"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41392-023-01502-8","article-title":"Inflammation and aging: Signaling pathways and intervention therapies","volume":"8","author":"Li","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of aging: An expanding universe","volume":"186","author":"Blasco","year":"2023","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nri3547","article-title":"Age-dependent dysregulation of innate immunity","volume":"13","author":"Shaw","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nature12984","article-title":"The bone marrow niche for haematopoietic stem cells","volume":"505","author":"Morrison","year":"2014","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/s41586-024-07238-x","article-title":"Depleting myeloid-biased haematopoietic stem cells rejuvenates aged im munity","volume":"628","author":"Ross","year":"2024","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1182\/blood.2022017514","article-title":"Fecal microbiota transplantation from young mice rejuvenates aged hema topoietic stem cells by suppressing inflammation","volume":"141","author":"Zeng","year":"2023","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/s41419-024-06863-8","article-title":"mtDNA release promotes cGAS-STING activation and accelerated aging of postmitotic muscle cells","volume":"15","author":"Li","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/s42003-024-06386-0","article-title":"Apoptosis signal-regulating kinase 1 promotes inflammation in senescen ce and aging","volume":"7","author":"Odawara","year":"2024","journal-title":"Commun. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.exger.2016.09.016","article-title":"The effects of resveratrol on aging vessels","volume":"85","author":"Diaz","year":"2016","journal-title":"Exp. Gerontol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2412950","DOI":"10.1002\/advs.202412950","article-title":"Targeting Senescence with Apigenin Improves Chemotherapeutic Efficacy and Ameliorates Age-Related Conditions in Mice","volume":"12","author":"Zhang","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1038\/s42255-021-00491-8","article-title":"The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice","volume":"3","author":"Xu","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_16","unstructured":"(2001). Laboratory Animals\u2014Hygienic Standard for Formula Feeds (Standard No. GB\/T 14924.2-2001)."},{"key":"ref_17","unstructured":"(2010). Laboratory Animals\u2014Nutrients for Formula Feeds (Standard No. GB 14924.3-2010)."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13046-022-02248-x","article-title":"SMARCA5 interacts with NUP98-NSD1 oncofusion protein and sustains hematopoietic cells transformation","volume":"41","author":"Jevtic","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1016\/S0140-6736(22)01546-X","article-title":"The path to healthy ageing in China: A Peking University-Lancet Commission","volume":"400","author":"Chen","year":"2022","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"eaan4673","DOI":"10.1126\/science.aan4673","article-title":"Clonal hematopoiesis in human aging and disease","volume":"366","author":"Jaiswal","year":"2019","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Garc\u00eda, V., Gonz\u00e1lez-Ramos, S., Mart\u00edn-Sanz, P., Castrillo, A., and Bosc\u00e1, L. (2020). Contribution of Extramedullary Hematopoiesis to Atherosclerosis. The S pleen as a Neglected Hub of Inflammatory Cells. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.586527"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.immuni.2013.10.010","article-title":"The spleen in local and systemic regulation of immunity","volume":"39","author":"Bronte","year":"2013","journal-title":"Immunity"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/imm.12590","article-title":"Disorganization of the splenic microanatomy in ageing mice","volume":"148","author":"Aw","year":"2016","journal-title":"Immunology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1097\/00029330-200603020-00013","article-title":"Expression of tissue inhibitor of matrix metalloproteinase-1 in aging of transgenic mouse liver","volume":"119","author":"Zhang","year":"2006","journal-title":"Chin. Med. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1172\/JCI67674","article-title":"Rapamycin extends murine lifespan but has limited effects on aging","volume":"123","author":"Neff","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/ki.2008.319","article-title":"The aging kidney","volume":"74","author":"Zhou","year":"2008","journal-title":"Kidney Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1093\/ndt\/gfp232","article-title":"Ageing mouse kidney\u2014Not always the SAME old story","volume":"24","author":"Schmitt","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1053\/j.ackd.2010.05.002","article-title":"The Aging Kidney: Physiological Changes","volume":"17","author":"Weinstein","year":"2010","journal-title":"Adv. Chronic Kidney Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nature16932","article-title":"Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan","volume":"530","author":"Baker","year":"2016","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1172\/JCI200522675","article-title":"Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair","volume":"115","author":"Duffield","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eadp5239","DOI":"10.1126\/sciadv.adp5239","article-title":"Beta2 adrenergic receptor-mediated abnormal myelopoiesis drives neuroi nflammation in aged patients with traumatic brain injury","volume":"10","author":"Jiang","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e154333","DOI":"10.1172\/JCI154333","article-title":"Myeloid FoxO1 depletion attenuates hepatic inflammation and prevents n onalcoholic steatohepatitis","volume":"132","author":"Lee","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e13094","DOI":"10.1111\/acel.13094","article-title":"Tissue specificity of senescent cell accumulation during physiologic a nd accelerated aging of mice","volume":"19","author":"Yousefzadeh","year":"2020","journal-title":"Aging Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.cell.2011.07.030","article-title":"Autophagy and aging","volume":"146","author":"Rubinsztein","year":"2011","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2933","DOI":"10.1007\/s11357-024-01092-5","article-title":"Longevity and anti-aging effects of curcumin supplementation","volume":"46","author":"Izadi","year":"2024","journal-title":"Geroscience"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10709","DOI":"10.1080\/10408398.2022.2084600","article-title":"Health benefits of astaxanthin against age-related diseases of multipl e organs: A comprehensive review","volume":"63","author":"Alugoju","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.jaad.2004.12.044","article-title":"Green tea and the skin","volume":"52","author":"Hsu","year":"2005","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.phymed.2013.11.001","article-title":"The Chinese herbal formula Liuwei dihuang protects dopaminergic neuron s against Parkinson\u2019s toxin through enhancing antioxidative defense and preventing apoptotic death","volume":"21","author":"Tseng","year":"2014","journal-title":"Phytomedicine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"117694","DOI":"10.1016\/j.jep.2023.117694","article-title":"The function of Bazhen decoction in rescuing progeroid cell senescence via facilitating G-quadruplex resolving and telomere elongation","volume":"323","author":"Li","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.cmet.2016.09.013","article-title":"Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age- Associated Physiological Decline in Mice","volume":"24","author":"Mills","year":"2016","journal-title":"Cell Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e14273","DOI":"10.1111\/acel.14273","article-title":"Cytochrome b5 reductase 3 overexpression and dietary nicoti namide riboside supplementation promote distinctive mitochondrial alte rations in distal convoluted tubules of mouse kidneys during aging","volume":"23","author":"Moreno","year":"2024","journal-title":"Aging Cell"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/12\/922\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T04:34:22Z","timestamp":1781843662000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/12\/922"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,12]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["biology15120922"],"URL":"https:\/\/doi.org\/10.3390\/biology15120922","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,12]]}}}