The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age
Open accessAbstract
Significance: A hallmark of aging is chronic sterile inflammation, which is closely associated with frailty and age-related diseases. We found that senescent fat progenitor cells accumulate in adipose tissue with aging and acquire a senescence-associated secretory phenotype (SASP), with increased production of proinflammatory cytokines compared with nonsenescent cells. These cells provoked inflammation in adipose tissue and induced macrophage migration. The JAK pathway is activated in adipose tissue with aging, and the SASP can be suppressed by inhibiting the JAK pathway in senescent cells. JAK1/2 inhibitors reduced inflammation and alleviated frailty in aged mice. One possible mechanism contributing to reduced frailty is SASP inhibition. Our study points to the JAK pathway as a potential target for countering age-related dysfunction.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Sncs can directly cause insulin resistance through release of SASP factors such as IL-6 and TNF-α (39, 40).”
From Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span (2021) · cites this paper as [39]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“We showed that aged 3xTg-AD male mice in particular, exhibit elevated plasma levels of known SASP factors [65, 66], including IL-12, IL-10, IL-6, CXCL2, CXCL1, and G-CSF”
From Age, sex and Alzheimer’s disease: a longitudinal study of 3xTg-AD mice reveals sex-specific disease trajectories and inflammatory responses mirrored in postmortem brains from Alzheimer’s patients (2024) · cites this paper as [66]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“This concept is supported by a study of aged mice demonstrating that pharmacologic inhibition of the JAK pathway, which regulates the SASP in senescent preadipocytes and endothelial cells in vitro, suppresses markers of both adipose tissue and systemic inflammation and improved parameters of muscle strength, endurance, and coordination (39).”
From Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span (2021) · cites this paper as [39]
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, JAK inhibitors alleviated frailty in aged mice99.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [99]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Similarly, other inhibitors of proinflammatory signalling (e.g. JAK/STAT [124] and p38 [60]) and antibodies targeting IL-6 [125], IL-1 [126] and TNFa [127], might be potentially effective senomorphic drugs.”
From The role of cellular senescence and SASP in tumour microenvironment (2023) · cites this paper as [124]
In the citing paper
“Alternatively, it is possible to modulate individual components of the SASP by inhibiting Janus kinase (JAK) 1/2148 and JAK2/signal transducer and activator of transcription 3 (STAT3).149”
From Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis (2020) · cites this paper as [148]
In the citing paper
“Similarly, the inhibition of pro-inflammatory JAK signalling in the same model was shown to attenuate pathogenesis by reducing the infiltration of monocytes to the lung130–132.”
From COVID-19 and cellular senescence (2023) · cites this paper as [131]
In the citing paper
“However, senomorphic treatment may require continuous administration and could potentially disrupt tissue homeostasis due to SASP blockade.”
From Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies (2024) · cites this paper as [192]
In the citing paper
“In terms of alleviating age-related phenotypes, minimizing the SASP using Janus kinase/signal transducer and activator of transcription (JAK/STAT) inhibition is very similar to eliminating or reducing the burden of senescent cells genetically (e.g., using INK-ATTAC mice) or pharmacologically with senolytic agents [4, 11, 13, 60].”
From Reducing Senescent Cell Burden in Aging and Disease (2020) · cites this paper as [13]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Frailty in Older Adults: Evidence for a Phenotype
Fried, L. P., Tangen, C. M., Walston, J., Newman, A. B., Hirsch, C., Gottdiener, J., Seeman, T., Tracy, R., Kop, W. J., Burke, G., et al. (2001) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/56.3.m146 · Cited by 24,907
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982
The metabolic phenotype in obesity: Fat mass, body fat distribution, and adipose tissue function
Goossens, G. H. (2017) · Obesity Facts · doi:10.1159/000471488 · Cited by 8,481
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
STATs in cancer inflammation and immunity: a leading role for STAT3
Yu, H., Pardoll, D., & Jove, R. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2734 · Cited by 4,383
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · cited 4×
“(iii) p16positive senescent cells were the main cause of increased IL-6 expression in the stromal vascular fraction of adipose tissue digests from older progeroid mice (21).”
BackgroundMethodInfluentialSelf-citationPrinciples of interleukin (IL)-6-type cytokine signalling and its regulation
HEINRICH, P. C., BEHRMANN, I., HAAN, S., HERMANNS, H. M., MÜLLER-NEWEN, G., & SCHAPER, F. (2003) · Biochemical Journal · doi:10.1042/bj20030407 · Cited by 3,272 · cited 1×
“IL-6, a major SASP component, signals through the JAK/ STAT pathway (61) and has been shown to be critical in stabilizing cellular senescence (62).”
Background
Cited by
Sorted by citations
Items 601–700 of 921
The IGF-1 senescence switch: a biphasic model for SASP-driven aging and precision senomodulation
Manni, E., Al‐kuraishy, H. M., Hussain, N. R., Abdelaziz, A. M., & Batiha, G. E. (2026) · Cytokine · doi:10.1016/j.cyto.2026.157143 · Cited by 8
Aging and Autophagy: Roles in Musculoskeletal System Injury
Zhang, H., Gu, W., Wu, G., & Yu, Y. (2024) · Aging and Disease · doi:10.14336/ad.2024.0362 · Cited by 7
“In addition, it contributes to the degeneration of intervertebral discs, senile osteoporosis, and arthritis and tendon disorders caused by the aging of the tendons [30-33].”
Palmer, A. K., Jensen, M. D., Tchkonia, T., & Kirkland, J. L. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822514-1.00009-2 · Cited by 7
Self-citationML216 Prevents DNA Damage-Induced Senescence by Modulating DBC1–BLM Interaction
Cui, F., Han, X., Zhang, X., Wang, S., Liang, N., Tan, Q., Sha, W., & Li, J. (2022) · Cells · doi:10.3390/cells12010145 · Cited by 7
“Currently available intervention strategies targeting senescence include senolytics, which induce apoptosis in senescent cells [13,14], and senomorphics, which suppress the secretory phenotypes of senescent cells [15,16].”
BackgroundCell Senescence in Heterotopic Ossification
Pignolo, R. J., Kaplan, F. S., & Wang, H. (2024) · Biomolecules · doi:10.3390/biom14040485 · Cited by 7
“In addition, activin A is a factor described as part of the SASP [34,35] and the mutated ACVR1/ALK2 BMP type I receptor in FOP aberrantly responds to activin A [36].”
Inflammaging and age-associated diseases
Manabe, I. (2017) · Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics · doi:10.3143/geriatrics.54.105 · Cited by 7
Targeting senescent cells and tumor therapy (Review)
Wang, Z., Gao, J., Liu, H., Ohno, Y., & Xu, C. (2020) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2020.4705 · Cited by 8
“Xu et al (41) demonstrated that JAK inhibitors reduce the secretion of SASP in adipocyte precursor cells and human umbilical vein endothelial cells (HUVEcs), suggesting that the JAK pathway is a potential target for anti-senescence-associated treatments.”
BackgroundCao, J., Li, J., Yang, X. L., Li, P., Yao, Z., Han, D., Ying, L., Wang, L., & Tian, J. (2021) · Scientific Reports · doi:10.1038/s41598-020-80065-y · Cited by 8
Recent Advances in Senotherapeutics Delivery
Choi, J. Y., Yee, S. F., Tchangalova, T., Yang, G., & Fisher, J. P. (2022) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2021.0212 · Cited by 6
“22–24 The JAK-STAT signaling pathway is involved in maintaining cell homeostasis and developmental processes such as stem cell maintenance, apoptosis, immunity, and organismal development.”
Local and systemic impact of adipocyte senescence-associated secretory profile
Wan, Y. C. E., Dufau, J., & Spalding, K. L. (2024) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2024.100547 · Cited by 8
Krüger, P., Schroll, M., Fenzl, F. Q., Hartinger, R., Lederer, E.-M., Görlach, A., Gordon, L. B., Cavalcante, P., Iacomino, N., Rathkolb, B., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26104849 · Cited by 6
“These cytokines activate the JAK/STAT pathway, which not only drives the expression of genes involved in pathogen clearance but also contributes to senescence induction [32–36].”
Rademacher, D. J., Exline, J. E., & Foecking, E. M. (2025) · Biomedicines · doi:10.3390/biomedicines13061400 · Cited by 8
Distinct precursor landscape of subcutaneous and visceral fat in development and aging
Lin, F., & Sul, H. S. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116706 · Cited by 7
“118,119 These cells impact the neighboring adipose precursors by secreting inflammatory factors and impairing adipogenesis.”
Kourti, M., & Kontoghiorghes, G. J. (2025) · Antioxidants · doi:10.3390/antiox15010015 · Cited by 11
“JAK inhibitors, including ruxolitinib, are under evaluation for reducing SASP-driven inflammation in chronic inflammatory and fibrotic diseases and may hold promise for age-related conditions [270].”
Regenerative therapeutics for chronic obstructive pulmonary disease
van der Koog, L., Showell, H., Nugraha, D. F., Lehmann, M., Conlon, T. M., Yildirim, A. Ö., Fuentes‐Mateos, R., Baarsma, H. A., Ng-Blichfeldt, J.-P., Melgert, B. N., et al. (2026) · Pharmacological Reviews · doi:10.1016/j.pharmr.2026.100124 · Cited by 8
Wu, X., Niu, K., Wang, X., Zhao, J., Wang, H., Li, D., Wang, H., Miao, T., Yang, Y., Ma, H., et al. (2021) · Genetics · doi:10.1093/genetics/iyab234 · Cited by 6
Chen, Y., Wu, J., Wong, C., Gao, W., Qi, X., & Zhou, H. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05302-3 · Cited by 7
Kasprzyk-Pawelec, A., Tan, M., Rahhal, R., McIntosh, A. T., Fernandez, H. R., Mosaoa, R., Jiang, L., Pearson, G. W., Glasgow, E. F., Vockley, J., et al. (2024) · Cell Death and Differentiation · doi:10.1038/s41418-024-01428-w · Cited by 15
“Oncogene induced senescence (OIS), is characterized by the secretion of pro-in fl ammatory mediators IL-6, IL-1 β , and IL-1 α , and involves the activity of several downstream effectors, including NFkB, mTOR, AP1/MAPK signaling, and the JAK/STAT pathway [19 – 22].”
The effects of glipizide on DNA damage and nuclear transport in differentiated 3T3-L1 adipocytes
Çevik, M., Caker, S., Deliorman, G., Çağatay, P., Gündüz, M. K., & Duman, B. S. (2022) · Molecular Biology Reports · doi:10.1007/s11033-021-06942-5 · Cited by 6
“Compared to mature adipocytes, older adipocytes have been reported to be associated with higher insulin resistance, lower glucose deposition and energy expenditure, and deterioration of fatty acid esterification [18, 19].”
BackgroundOral Senescence: From Molecular Biology to Clinical Research
Parkinson, E. K., & Prime, S. S. (2022) · Frontiers in Dental Medicine · doi:10.3389/fdmed.2022.822397 · Cited by 7
“Such targets include p38 mitogenactivated kinase (MAPK14; (86), p38 MAPKAPK2/3 (87), Janusactivated kinase 1 (JAK1; (88) and steroids (89); these drugs have been shown to ameliorate the effects of frailty (88) and type 2 diabetes in mice (90).”
BackgroundBrief about hallmarks of aging
Esposto, J., & Balendra, V. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-90235-9.00006-9 · Cited by 6
Liu, A., Wang, X., Liu, H., Yan, D., Yin, Y., Zheng, H., Liu, G., Zhang, J., & Li, Y. (2023) · PLoS ONE · doi:10.1371/journal.pone.0287132 · Cited by 6
“There are also some evidences indicating that the JAK/STAT signaling pathway in senescent cells is more active than non-senescent cells and inhibition of the pathway can suppress the aging-related secretory phenotype and alleviate dysfunction in senescent cells [59].”
BackgroundCellular Senescence in Craniofacial Tissue Regeneration: Inducers, Biomarkers, and Interventions
Tang, W., Huo, F., Long, J., Zhang, S., & Tian, W. (2023) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2023.0136 · Cited by 6
Application potential of senolytics in clinical treatment
Li, T., Li, S., Ma, K., & Kong, J. (2023) · Biogerontology · doi:10.1007/s10522-023-10084-5 · Cited by 6
“In addition, senescent cells generally can directly promote insulin resistance by secreting SASP factors such as activin A, IL 6 and TNF (Xu et al. 2015; Liu et al. 2016).”
Trzaskoma, P., Jung, S., Kanno, Y., O’Shea, J. J., & Chow, C. C. (2024) · Neoplasia · doi:10.1016/j.neo.2024.101071 · Cited by 6
“For example, the JAK/STAT pathway has been shown to be activated in aged tissues [31,32] and during replicative senescence [49].”
Prevention of Senescence in Vasculature Through Quiescence
Mendelsohn, A. R., & Larrick, J. W. (2018) · Rejuvenation Research · doi:10.1089/rej.2018.2138 · Cited by 6
Network Topology of Biological Aging and Geroscience-Guided Approaches to COVID-19
LANDAY, A. L., Bartley, J. M., Banerjee, D., Hargis, G. R., Haynes, L., Keshavarzian, A., Kuo, C., Kwon, O. S., Li, S., Li, S., et al. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.695218 · Cited by 6
Self-citationAltered Regulation of adipomiR Editing with Aging
Meadows, S., Seidler, A., Wall, M., Page, J., Taylor, C., Flinn, B. B., Turner, R., & Santanam, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186899 · Cited by 6
Calvo, L., Cheng, S., Skulimowski, M., Clément, I., Portelance, L., Zhan, Y., Carmona, E., Lafontaine, J., de Ladurantaye, M., Rahimi, K., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/425199 · Cited by 6
“, 2007), further guiding potential senescence pharmacological avenues toward SAPA reinforcement, SASP manipulation, and potential senescent cancer cell elimination via senolysis (Chang et al., 2016; Laberge et al., 2015; Moiseeva et al., 2013; Pan et al., 2017; Rader et al., 2013; Xu et al., 2015; Yosef et al., 2016;…”
BackgroundAdipose Tissue Plasticity in Aging
Wang, G., Song, A., Bae, M., & Wang, Q. A. (2022) · Comprehensive physiology · doi:10.1002/cphy.c220005 · Cited by 9
Heinze-Milne, S., Hodgins, M. L., & Howlett, S. E. (2025) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2025.112054 · Cited by 5
“Higher circulating levels of IL-6 are associated with components of physical frailty (Xu et al., 2015) and can play a major role in frailty progression in mice (Jergovi ´ c et al., 2021) and humans (McKechnie et al., 2021).”
Pharmacological frontiers in senescence: Transforming senescence with drug repurposing
Shahzadi, A., Özyazgan, S., & Çakatay, U. (2025) · Advances in pharmacology · doi:10.1016/bs.apha.2025.02.010 · Cited by 5
Cellular senescence—from solid organs to vascularized composite allotransplants
Knoedler, L., Schroeter, A., Iske, J., Dean, J., Boroumand, S., Schaschinger, T., Niederegger, T., Knoedler, S. A., Panayi, A. C., Heiland, M., et al. (2025) · GeroScience · doi:10.1007/s11357-025-01788-2 · Cited by 6
“…the JAK/STAT pathway plays a dual role—while it facilitates immune surveillance and host defense, its prolonged activation in senescent skin cells undermines the integrity and regenerative capacity of the graft, making it a critical target for modulating inflammation post-transplantation [66, 67].”
The drug discovery and therapeutic nano-strategies targeting cellular senescence
Wang, Y., Liu, M., Chen, X., Wang, S., Li, J., Sun, Y., Zheng, X., Zhang, J.-X., & Li, H. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2025.102480 · Cited by 6
Senotherapeutics for metabolic disease and diabetic complications
Palmer, A. K., Spinelli, R., Prata, L. G. P. L., Chaib, S., Suda, M., Tchkonia, T., Smith, U., & Kirkland, J. L. (2025) · Journal of Internal Medicine · doi:10.1111/joim.70039 · Cited by 6
Self-citationCadar, A. N., Torrance, B. L., Fischler, S. A., Djaba, D. A., Haddad, Z. L., Teskey, D. E., Nagaraju, M., Gorgei, K. A., Lorenzo, E. C., Haynes, L., et al. (2025) · Aging Cell · doi:10.1111/acel.70345 · Cited by 5
“Age-related accumulation of senescent cells has been shown to have a causal role in frailty (Xu et al. 2015), declines in physical function (Xu et al. 2018), and age-related bone loss (Farr et al. 2017) among other disorders.”
Evaluating senescence-targeted approaches in Alzheimer’s Disease: What we know and what lies ahead
Doshi, P. P., Desale, S. H., Khutale, A. A., Sabarathinam, S., & Suresh, S. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103029 · Cited by 7
Senescent Schwann cells as therapeutic targets in nerve regeneration and peripheral neuropathies
Rebolledo, D. L., Khan, M., Melov, S., Höke, A., & Court, F. A. (2026) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2026.01.003 · Cited by 5
Cantero‐Fortiz, Y., Butler, C., Montalbán, X., & Boada, M. (2026) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2026.1805691 · Cited by 6
“Similarly, JAK inhibitors such as ruxolitinib and p38 MAPK inhibitors have demonstrated efficacy in downregulating the SASP and restoring tissue homeostasis (Riessland et al., 2024; Riessland et al., 2024; Xu et al., 2015; Hongo et al., 2017).”
He, E., Sui, H.-T., Wang, H., Zhao, X., Guo, W., Dai, Z., Wu, Z.-K., Huang, K., & Zhao, Q.-H. (2024) · Stem Cell Reviews and Reports · doi:10.1007/s12015-024-10709-3 · Cited by 5
Ruxolitinib Delays Nucleus Pulposus Cell Senescence in Rat Intervertebral Discs
Hao, H., Liang, W., Zhang, S., Cai, X., Abulizi, Y., Gao, S., Xun, C., Xu, T., Cao, R., & Sheng, W. (2025) · JOR Spine · doi:10.1002/jsp2.70044 · Cited by 6
“Modulation of STAT3 using a JAK inhibitor decreases SASP expression and secretion in senescent adipose precursor cells and umbilical vein vascular endothelial cells [10].”
Giroud, J., Delvaux, P., Carlier, L., de Schutter, C., Martin, N., Rouget, R., Bolouki, A., Glas, V. D., Bouriez, I., Bourdoux, F., et al. (2025) · Aging Cell · doi:10.1111/acel.70024 · Cited by 7
“Nevertheless, it has been shown that the secretome from senescent preadipocytes treated with ruxolitinib (a JAK inhibitor) prevents macrophage migration, reduces inflammation in nonsenescent preadipocytes (Xu et al. 2015), and attenuates osteoclast differentiation (Farr et al. 2017).”
In vitro senescence and senolytic functional assays
Ryan, P., & Lee, J. (2025) · Biomaterials Science · doi:10.1039/d4bm01684j · Cited by 7
Telomerase Depletion Accelerates Ageing of the Zebrafish Brain
Martins, R. R., Besse, S., Ellis, P. S., Sevil, R., Hartopp, N., Purse, C., Everett‐Brown, G., Evans, O., Mughal, N., Wahib, M. H. F., et al. (2025) · Aging Cell · doi:10.1111/acel.70280 · Cited by 5
Gijsen, H. S. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-55035-6_16 · Cited by 6
Rad, A. N., Shams, G., Avelar, R. A., Morowvat, M. H., & Ghasemi, Y. (2022) · Informatics in Medicine Unlocked · doi:10.1016/j.imu.2022.100920 · Cited by 4
Cai, G., Xiao, Y., Yang, M., Guo, Q., Su, T., Liu, Y., Jiang, T., & Li, C. (2022) · PeerJ · doi:10.7717/peerj.13475 · Cited by 5
“These factors are termed the senescence associated secretory phenotype (SASP) ( Xu et al., 2015 ), which may contribute to impaired therapeutic effects of senescent BMSCs ( Sepulveda et al., 2014 ; Turinetto, Vitale & Giachino, 2016 ).”
Finding Shangri-La: Limiting the Impact of Senescence on Aging
Trabucco, S. E., & Zhang, H. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.02.002 · Cited by 5
“Two recent studies (Chang et al., 2016; Xu et al., 2015a) now show that pharmacological inhibition of specific senescence pathways can rejuvenate aged stem cells and improve tissue functions in old mice (Figure 1).”
BackgroundInfluentialKasprzyk-Pawelec, A., Tan, M., Rahhal, R., McIntosh, A. T., Fernandez, H. R., Mosaoa, R., Jiang, L., Pearson, G. W., Glasgow, E. F., Vockley, J. E., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.18.549409 · Cited by 5
Impact of Aging and Cellular Senescence in the Pathophysiology of Preeclampsia
Suvakov, S. R., Kattah, A. G., Gojković, T., Enninga, E. A. L., Pruett, J. E., Jayachandran, M., Sousa, C., Santos, J., Hassan, C. A., Suarez, M. L. G., et al. (2023) · Comprehensive physiology · doi:10.1002/cphy.c230003 · Cited by 6
“While suppression of SASP has not been shown to decrease senescent cell burden, it has been demonstrated to alleviate frailty and age-associated chronic morbidities (547).”
Tendon Aging: A Silent Enemy Revealed Strategies for Effective Treatment
Gu, W., Wang, G., Zhang, H., & Yu, Y. (2025) · Aging Medicine · doi:10.1002/agm2.70027 · Cited by 4
“Thus, the inflammatory response occurring in tendons is believed to be driven by the over-differentiation of adipocytes and the accumulation of preadipocytes and adipocyte progenitor cells in the tendons of aging individuals [33].”
Decoding senescent drivers in Alzheimer's disease: From bench to bedside
Zhou, R., Lin, X., Liao, Z., Lin, J., Zheng, R., Ni, H., Liu, W., Feng, Z., He, Q., Lin, X., et al. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102978 · Cited by 4
Zhang, Y., Pei, Z., Wen, Z., Chen, Y., Wang, H., Tan, W., Chen, X. Y., Liu, J., & Ni, Q. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1706384 · Cited by 5
Correale, J. D. (2026) · Journal of Neurochemistry · doi:10.1111/jnc.70414 · Cited by 4
“…initially adaptive during acute responses, becomes self-reinforcing, locking cells into a state where metabolic resources shift away from trophic functions toward maintaining the senescence-associated secretory phenotype (SASP; García-García et al. 2021; Salminen et al. 2012; Xu et al. 2015).”
Chronic Kidney Disease and Cellular Senescence
Morevati, M., Tavenier, J., Scheibye‐Knudsen, M., Houlind, M. B., Hedayati, A., & Hornum, M. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27073205 · Cited by 4
“Another illustration of a senomorphic drug is ruxolitinib, a JAK inhibitor that mitigates inflammation and weakness in elderly mice by suppressing inflammatory components of the SASP [183].”
Treteanu, A. R., & Mirabela, M. M. (2026) · Brain Research · doi:10.1016/j.brainres.2026.150414 · Cited by 6
Inflammaging and osteoarthritis - therapeutic opportunities
Chan, M., Low, P., Ong, S. C., Choy, S. M., Lee, W. X., Goh, K. Y., Ng, K., Chua, K., Lee, J. Y., Guo, A. K., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1850495 · Cited by 4
“…signaling pathways, including the NF-k B pathway, p38 mitogen-activated protein kinase (MAPK/ p38) pathway, mammalian target of rapamycin (mTOR) pathway, AMP-activated protein kinase (AMPK) pathway, and Janus kinase/ signal transducers and activators of transcription (JAK/STAT) pathway (13).”
Sucularlı, C., Demir, Y. D. Ş., Özdemir, A., & Ark, M. (2024) · Biosystems · doi:10.1016/j.biosystems.2024.105140 · Cited by 4
Schultz, D. F., Davies, B. A., Payne, J. A., Martin, C. P., Minard, A. Y., Childs, B. G., Zhang, C., Jeganathan, K. B., Sturmlechner, I., White, T. A., et al. (2024) · Journal of Cell Science · doi:10.1242/jcs.262032 · Cited by 4
Self-citationMa, J., Yang, W., Chen, F.-M., He, Q., Ma, H.-L., Li, C., Liang, M.-L., Zhong, J.-Q., Zhang, X., & Li, F. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117068 · Cited by 4
Xie, J., Shu, X., Xie, Z., Tang, J., & Guo, W. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.177475 · Cited by 4
Huang, Y., Qiu, Z., Jiang, C., Fang, Q., Wang, J., Han, M., Liu, Y., & Li, Z. (2025) · Scientific Reports · doi:10.1038/s41598-025-00950-2 · Cited by 4
“Senescent cells may be one of the sources of chronic systemic inflammation: the senescence-associated secretory phenotype (SASP) is a group of proinflammatory cytokines, chemokines, and proteases secreted by senescent cells 9,24,25 , which collectively modify the local environment.”
Khosla, S. (2024) · Journal of Clinical Investigation · doi:10.1172/jci180558 · Cited by 4
“Conversely, reducing the SASP either through killing senescent cells using senolytics (4) or inhibiting the secretion of the SASP (e.g., using JAK inhibitors (8)) has now been shown to ameliorate a number of aging phenotypes, at least in mice.”
[The effect of deep branches of cervical nerve on motorial function of trapezius muscle].
Wang, F., Wen, Y., & Li, L. (2003) · PubMed · Cited by 4
Iwasaki, K., Carapeto, P., Abarca, C., Hela, F., Sanjines, S., Pena, S., Le, S., Pan, H., Jackson, M., Cahill, C., et al. (2026) · JCI Insight · doi:10.1172/jci.insight.197310 · Cited by 4
Self-citationCan hypoxic exercise retard cellular senescence? A narrative review
Huang, T., Tsang, C. S. L., & Huang, T. (2024) · European Review of Aging and Physical Activity · doi:10.1186/s11556-024-00352-9 · Cited by 3
Senotherapeutics: Milestones, innovations, and future prospects
Atasever, E., Atayik, M. C., & Çakatay, U. (2025) · Advances in pharmacology · doi:10.1016/bs.apha.2025.01.021 · Cited by 3
Unraveling senescence in cancer: mechanistic complexities and therapeutic opportunities
Tiwari, P., Shukla, S. K., & Verma, S. R. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-10630-z · Cited by 3
“In aged mice, inhibiting SASP in senescent preadipocytes lowered systemic inflam - mation and fever [44–49].”
Cellular senescence: A novel mechanism of therapeutic resistance in prostate cancer
Lin, C., Hadfield, M. J., Rathore, A., Pinho-Schwermann, M. P., Zhang, S., Lu, S., den Hollander, P., Mani, S. A., Seyhan, A. A., Santopietro, A., et al. (2025) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2025.103061 · Cited by 4
Ghosh, M., Wu, C., Kumar, A., Nilsson, M. B., Heymach, J. V., Zhao, W., Yu, J., Liu, X., Ding, N., Wang, S., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci198418 · Cited by 3
“Because IL-6 and TNF-α can drive EMT and drug resistance (36, 37), we utilized genetic and pharmacogic approaches to block SASP (38, 39).”
InfluentialYang, T.-J., Chen, T.-X., Zhang, Y., Luo, Y., & Wen, P.-P. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1653037 · Cited by 3
“This makes it a logical hypothesis that senolytics, or senomorphics that modulate the inflammatory secretory phenotype (144), could disrupt the local pathological cascade.”
Natural killer cell-based senotherapy: a promising strategy for healthy aging
中澤務, Yamanishi, R., Morimoto, T., & Matusda, R. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1737572 · Cited by 3
“In senescent fi broblasts and irradiated tissues, these agents reduced proin fl ammatory cytokines and improved regeneration (162).”
Senescence associated osteoarthritis: Emerging therapeutics and future directions
Razdan, S., Tomar, A., & Bawari, S. (2026) · Clinical Immunology Communications · doi:10.1016/j.clicom.2026.01.003 · Cited by 3
Osteoimmune senescence in aging-related bone diseases
Li, H., Yang, Y., & Zhu, H. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1892334 · Cited by 5
“JAK/STAT signaling is another SASP-related pathway with therapeutic relevance because JAK inhibition reduces senescence-associated in fl ammatory mediators in aging models (64).”
InfluentialExploiting senescence as a therapeutic target in osteoarthritis
Larbie, C., & Raza, U. (2024) · Asia-Pacific Journal of Pharmacotherapy & Toxicology · doi:10.32948/ajpt.2024.11.19 · Cited by 4
New approach methodologies in Crohn’s disease link molecular disease subtypes to clinical outcomes
Penrose, H. M., Sinha, S., Tindle, C., Zablan, K. M., Le, H. N., Neill, J., Ghosh, P., & Boland, B. S. (2026) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00393.2025 · Cited by 4
Consequences of senotherapies for tissue repair and reprogramming
van Vliet, T., Kohli, J. S., & Demaria, M. (2019) · Translational Medicine of Aging · doi:10.1016/j.tma.2019.01.003 · Cited by 3
Son, Y. H., Kim, W. J., Shin, Y. J., Lee, S.-M., Lee, B., Lee, K., Lee, S., Kim, K. J., & Kwon, K. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112273 · Cited by 3
Wyles, S. P., Vyas, K. S., Wasserburg, J. R., Ansaf, R. B., & Kirkland, J. L. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15500-0.00009-8 · Cited by 3
Self-citationGuilatco, A. J., Shah, M. V., & Weivoda, M. M. (2024) · Journal of bone oncology · doi:10.1016/j.jbo.2024.100620 · Cited by 4
“…for myelofibrosis and other inflammatory conditions, which has been shown to suppress the pro-inflammatory SASP from senescent human primary preadipocytes and human vascular endothelial cells (hUVEC); treatment of aged mice with ruxolitinib reduced systemic inflammation and alleviated frailty [77].”
BackgroundGerosuppressive and Senolytic Nutrients
Nehlin, J. O. (2021) · Healthy ageing and longevity · doi:10.1007/978-3-030-83017-5_22 · Cited by 3
Cytokine Receptors and Their Ligands
Shing, K. S. C. T., Kan, W. L., Nero, T. L., Hercus, T. R., Tvorogov, D., Metcalfe, R. D., Griffin, M. D. W., de Weerd, N. A., Guthridge, M. A., Hertzog, P. J., et al. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821618-7.00079-1 · Cited by 3
A single nuclei atlas of aging human abdominal subcutaneous white adipose tissuePreprint
Sparks, L. M., Whytock, K. L., Divoux, A., Sun, Y., Pino, M., Yu, G., Smith, S. R., & Walsh, M. J. (2023) · Research Square · doi:10.21203/rs.3.rs-3097605/v1 · Cited by 3
Diniz, B. S., Chen, Z., Steffens, D. C., Pilling, L. C., Fortinsky, R. H., Kuchel, G. A., & Kuo, C. (2024) · medRxiv · doi:10.1101/2024.09.11.24313493 · Cited by 3
“The overactivation of this pathway can lead to the inhibition of pro-apoptotic factors and induction of cellular senescence 68, 69 .”
BackgroundBene, M. R., Chung, T., Fountain, W. A., Rosales‐Soto, G., Hernández‐Ochoa, E. O., Antonescu, C. M., Florea, L., Jeong, S. J., Le, A., Xue, Q., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.30.667744 · Cited by 3
“Notably, ruxoliPnib has been shown to enhance physical performance in naturally aged and progeria mouse models, as well as to increase muscle mass in paPents with myelofibrosis (Xu et al. 2015; Griveau et al. 2020; Lucijanic et al. 2021).”
The role of senescence in cancer therapy-associated cardiovascular toxicity
Alshoubaki, Y. K., Grüterich, V., Zollet, V., & Kuster, G. M. (2024) · The Journal of Cardiovascular Aging · doi:10.20517/jca.2024.14 · Cited by 2
Aversa, Z., Frank, R. D., Geske, J. R., White, T. A., Heeren, A. A., Kapoor, E., Rocca, W. A., Schafer, M. J., Fields, J. A., Kantarci, K., et al. (2025) · Maturitas · doi:10.1016/j.maturitas.2025.108606 · Cited by 2
Self-citationDehkordi, S. K., Sajedi, S., Heshmat, A., Orr, M. E., & Zare, H. (2025) · npj Aging · doi:10.1038/s41514-025-00235-y · Cited by 2
The Role of Senolytics in Osteoporosis
Chen, E., Zhang, J., Chen, H., & Li, W. (2025) · Biomolecules · doi:10.3390/biom15081176 · Cited by 6
“…β -galactosidase-activated prodrugs and nanoparticles [73,74], apoptosis induction via sodium–potassium pump (Na+/K+-ATPase) modulation [75], SASP inhibition [76], and immune-mediated clearance approaches, including chimeric antigen receptor T cells, antibody–drug conjugates, and vaccines [77].”
o-Vanillin enhances bone health and fracture healing by inhibiting cellular senescence in aging mice
Ouyang, X., Geng, S., Abdullah, M., Geng, Y., Heng, K., Sha, L., Geng, Y., Nie, P., Liu, F., Zhai, J., et al. (2025) · Bone · doi:10.1016/j.bone.2025.117773 · Cited by 3
Conquering aging-related immunosenescence and tumor immune escape
Zhang, S., Yang, B., Xu, M., 邴英, Zhang, J., Wang, Y. L., Zheng, C., Zhang, G., & Zhang, L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1785351 · Cited by 2
“JAK inhibitors, on the other hand, directly interfere with the downstream signaling of key in fl ammatory cytokines such as IL-6 and IL-8, thereby attenuating the persistent disruptive in fl uence of SnCs on the immune microenvironment without affecting cell viability (150).”
Self-citationΠαπανικολάου, Κ., Yadav, A., Mankowski, R. T., Alexander, M. S., Gamboa, J. L., Thalacker‐Mercer, A. E., Dungan, C. M., & Englund, D. A. (2026) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00876.2025 · Cited by 2
Goo, B. M. S. S., Ahmadieh, S., Veerapaneni, P., Shi, H., Kim, D. S., Ogbi, M., Chouhaita, R., Cyriac, N., Cave, S., Liu, L., et al. (2026) · Aging Cell · doi:10.1111/acel.70519 · Cited by 2
“…senescent cell burden by senolytic, senomorphic, or genetic manipulations in aging models has been shown to improve adipose tissue function, including insulin sensitivity, glucose tolerance and adipogenesis (Palmer et al. 2019; Wang et al. 2022; Xu, Palmer, et al. 2015; Xu, Tchkonia, et al. 2015).”
Liu, F.-Y., Huang, Y.-P., Li, Z.-Q., Li, X., Zhang, J.-S., Guan, L., & Qiao, W.-J. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1746161 · Cited by 2
“Additionally, senomorphic strategies that suppress SASP (such as JAK inhibitors and NF-κ B inhibitors) may attenuate the detrimental paracrine effects of senescent cells (142).”
Wang, E., Wang, Y., Xu, Z., Zhang, Z., Wang, J., Jiang, Y., & Zhao, C. (2026) · Phytotherapy Research · doi:10.1002/ptr.70387 · Cited by 2
“Given the established role of JAK-STAT signaling in cytokine responses, SASPs, ROS-related DNA damage, and chronic inflammation (Xu et al. 2015, 2016), its suppression may further contribute to the protective effects of HT.”
Wei, R., Liu, D., Shu, K., & Zhu, H. (2026) · Drug Resistance Updates · doi:10.1016/j.drup.2026.101444 · Cited by 2
Cellular senescence during aging and chronic liver diseases
Jurk, D. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822514-1.00005-5 · Cited by 2
Novin, A., Wali, K. H., Pant, A., Liu, S., Du, W., Liu, Y., Wang, L., Xu, M., Wang, B., Suhail, Y., et al. (2024) · Cancers · doi:10.3390/cancers16050969 · Cited by 1
“Fat-derived ASCs (preadipocytes) were isolated from healthy lean kidney donors aged 39 ± 3.3 y with a body mass index of 26.6 ± 0.9 (mean ± SEM) [24].”
MethodInfluentialSelf-citationCellular senescence and PAPP-A
Conover, C. A. (2025) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2025.101637 · Cited by 2
Senotherapy: Implications for Transplantation
Jaros, M., & Melk, A. (2025) · Transplantation · doi:10.1097/tp.0000000000005291 · Cited by 2
Metadata
- Authors
- Xu, M., Tchkonia, T., Ding, H., Ogrodnik, M., Lubbers, E. R., Pirtskhalava, T., White, T. A., Johnson, K. O., Stout, M. B., Mezera, V., Giorgadze, N., Jensen, M. D., LeBrasseur, N. K., & Kirkland, J. L.
- Affiliations
- Mayo Clinic (US)
- Robert and Arlene Kogod Center on Aging,Mayo Clinic, Rochester, MN 55905;
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-11-02
- Volume
- 112
- Issue
- 46
- Pages
- E6301-10
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4655580
- OpenAlex
- W1932046626
- Cited by
- 915
- References
- 68
- Citations by year
- 2026: 104 · 2025: 110 · 2024: 112 · 2023: 98 · 2022: 110 · 2021: 115 · 2020: 72 · 2019: 70 · 2018: 59 · 2017: 30 · 2016: 33 · 2015: 1
- FWCI
- 30.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- HHS | NIH | National Institute on Aging (AG041122, AG013925)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- JAK inhibition, cellular senescence, senescence-associated secretory phenotype, frailty, aging, age-related inflammation, adipose tissue, preadipocytes, macrophage migration, conditioned medium, endothelial cells, physical function, JAK inhibitors
- MeSH terms
- Adipose Tissue, Animals, Cell Movement, Extracellular Matrix, Humans, Macrophages, Signal Transduction, Cellular Senescence, Adipocytes, RNA, Small Interfering, Mice, Janus Kinases, Human Umbilical Vein Endothelial Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
