Perspective: Targeting the JAK/STAT pathway to fight age-related dysfunction
Open accessAbstract
Senescent cells accumulate in a variety of tissues with aging. They can develop a senescence-associated secretory phenotype (SASP) that entails secretion of inflammatory cytokines, chemokines, proteases, and growth factors. These SASP components can alter the microenvironment within tissues and affect the function of neighboring cells, which can eventually lead to local and systemic dysfunction. The JAK pathway is more highly activate in senescent than non-senescent cells. Inhibition of the JAK pathway suppresses the SASP in senescent cells and alleviates age-related tissue dysfunction. Targeting senescent cells could be a promising way to improve healthspan in aged population.
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Minimizing the SASP using JAK/STAT inhibition is very similar to eliminating or reducing senescent cell burden genetically or pharmacologically with senolytics.
“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 [60]
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The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508 · cited 1× · see citing works
“Cellular senescence refers to a state of irreversible proliferative arrest in replicationcompetent cells (2) and has been associated with many age-related diseases (3–5).”
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 · see citing works
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 · cited 1× · see citing works
“The JAK/STAT (Janus kinase/signal transducer and activator of transcription) pathway is one of the major mechanisms that regulates cytokine production (22, 23).”
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766 · cited 1× · see citing works
“It was shown to extend lifespan in mice (43), while it had limited effects on age-related tissue dysfunction (44).”
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 1× · see citing works
“Furthermore, genetic or pharmacological senescent cell clearance in progeroid mice (15) or naturally aged mice (17) alleviated frailty.”
Self-citationA Gain-of-Function Mutation of <i>JAK2</i> in Myeloproliferative Disorders
Kralovics, R., Passamonti, F., Buser, A. S., Teo, S.-S., Tiedt, R., Passweg, J. R., Tichelli, A., Cazzola, M., & Skoda, R. C. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051113 · Cited by 3,470 · see citing works
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,891 · cited 1× · see citing works
“We found that genetic clearance of senescent cells improved adipogenesis in fat tissue in older, naturally-aged mice (20), a finding that was subsequently confirmed by others (39).”
Cellular senescence: from physiology to pathology
Muñoz-Espín, D., & Serrano, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3823 · Cited by 2,818 · see citing works
The Achilles' heel of senescent cells: from transcriptome to senolytic drugs
Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., et al. (2015) · Aging Cell · doi:10.1111/acel.12344 · Cited by 2,562 · cited 1× · see citing works
“Furthermore, genetic or pharmacological senescent cell clearance in progeroid mice (15) or naturally aged mice (17) alleviated frailty.”
Self-citationA complex secretory program orchestrated by the inflammasome controls paracrine senescence
Acosta, J. C., Banito, A., Wuestefeld, T., Georgilis, A., Janich, P., Morton, J. P., Athineos, D., Kang, T.-W., Lasitschka, F., Andrulis, M., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2784 · Cited by 2,278 · cited 1× · see citing works
“Senescent cells appear to be able to spread senescence to nearby cells (18, 19).”
A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis
Verstovsek, S., Mesa, R. A., Gotlib, J., Levy, R. S., Gupta, V., DiPersio, J. F., Catalano, J. V., Deininger, M., Miller, C., Silver, R. T., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1110557 · Cited by 2,103 · see citing works
Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
Kuilman, T., Michaloglou, C., Vredeveld, L. C. W., Douma, S., van Doorn, R., Desmet, C. J., Aarden, L. A., Mooi, W. J., & Peeper, D. S. (2008) · Cell · doi:10.1016/j.cell.2008.03.039 · Cited by 2,086 · see citing works
An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA
Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R.-M., Vijg, J., Van Steeg, H., Dollé, M. E. T., et al. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.11.012 · Cited by 2,045 · see citing works
Cellular senescence and the senescent secretory phenotype: therapeutic opportunities
Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J., & Kirkland, J. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64098 · Cited by 1,774 · cited 1× · see citing works
“Aging is one of the leading risk factors for a variety of age-related diseases, including atherosclerosis, most cancers, diabetes, osteoporosis, neurodegeneration, and frailty (1).”
Self-citationMetformin improves healthspan and lifespan in mice
Martin-Montalvo, A., Mercken, E. M., Mitchell, S. J., Palacios, H. H., Mote, P. L., Scheibye-Knudsen, M., Gomes, A. P., Ward, T. M., Minor, R. K., Blouin, M.-J., et al. (2013) · Nature Communications · doi:10.1038/ncomms3192 · Cited by 1,445 · cited 1× · see citing works
“It has been shown to improve physical function, increase insulin sensitivity, and reduce lipotoxicity in aged mice (45), effects similar to those of JAK inhibitors.”
Safety and Efficacy of INCB018424, a JAK1 and JAK2 Inhibitor, in Myelofibrosis
Verstovšek, S., Kantarjian, H. M., Mesa, R. A., Pardanani, A. D., Cortes, J. E., Thomas, D. A., Estrov, Z. E., Fridman, J. S., Bradley, E. C., Erickson‐Viitanen, S., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1002028 · Cited by 1,165 · cited 1× · see citing works
“JAK inhibitors can have side effects, including anemia and thrombocytopenia, at least in human subjects with myelofibrosis (46, 48).”
Laberge, R.-M., Sun, Y., Orjalo, A. V., Patil, C. K., Freund, A., Zhou, L., Curran, S. C., Davalos, A. R., Wilson-Edell, K. A., Liu, S., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3195 · Cited by 1,160 · see citing works
Janus kinases in immune cell signaling
Ghoreschi, K., Laurence, A., & O’Shea, J. J. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00754.x · Cited by 1,149 · cited 1× · see citing works
“JAK3 is principally expressed in cells of the hematopoietic lineage and is involved in erythropoietin signaling and immune function (25, 26).”
Fat tissue, aging, and cellular senescence
Tchkonia, T., Morbeck, D. E., Von Zglinicki, T., Van Deursen, J., Lustgarten, J., Scrable, H., Khosla, S., Jensen, M. D., & Kirkland, J. L. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00608.x · Cited by 1,094 · see citing works
Self-citationProinflammatory Cytokines, Aging, and Age-Related Diseases
Michaud, M., Balardy, L., Moulis, G., Gaudin, C., Peyrot, C., Vellas, B., Cesari, M., & Nourhashemi, F. (2013) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2013.05.009 · Cited by 1,094 · cited 1× · see citing works
“In addition, since frailty is highly associated with inflammation (47), we speculate that JAK inhibitor treatment might be more effective in patients with a high level of inflammation.”
Xu, M., Tchkonia, T., Ding, H., Ogrodnik, M., Lubbers, E. R., Pirtskhalava, T., White, T. A., Johnson, K. O., Stout, M. B., Mezera, V., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515386112 · Cited by 915 · cited 15× · see citing works
“These SASP components can alter the microenvironment within tissues and affect the function of neighboring cells, which can eventually lead to local and systemic dysfunction.”
InfluentialSelf-citationQuintás-Cardama, A., Vaddi, K., Liu, P., Manshouri, T., Li, J., Scherle, P. A., Caulder, E., Wen, X., Li, Y., Waeltz, P., et al. (2010) · Blood · doi:10.1182/blood-2009-04-214957 · Cited by 843 · cited 2× · see citing works
“Due to the role of JAK pathways in immune responses, we tested the effect of the JAK1/2 inhibitor on peripheral blood immune cells in aged mice and found no substantial change in either young or aged mice, which is consistent with previous findings (38).”
A senescent cell bystander effect: senescence‐induced senescence
Nelson, G., Wordsworth, J., Wang, C., Jurk, D., Lawless, C., Martin‐Ruiz, C., & von Zglinicki, T. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00795.x · Cited by 755 · cited 1× · see citing works
“Senescent cells appear to be able to spread senescence to nearby cells (18, 19).”
Roos, C. M., Zhang, B., Palmer, A. K., Ogrodnik, M. B., Pirtskhalava, T., Thalji, N. M., Hagler, M., Jurk, D., Smith, L. A., Casaclang‐Verzosa, G., et al. (2016) · Aging Cell · doi:10.1111/acel.12458 · Cited by 738 · see citing works
Self-citationDNA damage response and cellular senescence in tissues of aging mice
Wang, C., Jurk, D., Maddick, M., Nelson, G., Martin‐Ruiz, C., & Von Zglinicki, T. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00481.x · Cited by 696 · see citing works
Moiseeva, O., Deschênes‐Simard, X., St‐Germain, E., Igelmann, S., Huot, G., Cadar, A. E., Bourdeau, V., Pollak, M. N., & Ferbeyre, G. (2013) · Aging Cell · doi:10.1111/acel.12075 · Cited by 654 · cited 1× · see citing works
“In addition to JAK inhibitors, other compounds have been noted to suppress SASP components, including metformin (40), rapamycin (41), and glucocorticoids (42).”
Modulation of Innate and Adaptive Immune Responses by Tofacitinib (CP-690,550)
Ghoreschi, K., Jesson, M. I., Xiong, L., Lee, J. L., Ghosh, S., Alsup, J. W., Warner, J. D., Tanaka, M., Steward-Tharp, S. M., Gadina, M., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003668 · Cited by 642 · cited 1× · see citing works
“Other inhibitors that target different JAKs are in clinical trials for treating myelofibrosis (22, 30), acute myeloid leukemia (31), lymphoma (32), and rheumatoid arthritis (22, 33, 34).”
Targeting senescent cells enhances adipogenesis and metabolic function in old age
Xu, M., Palmer, A. K., Ding, H., Weivoda, M. M., Pirtskhalava, T., White, T. A., Sepe, A., Johnson, K. O., Stout, M. B., Giorgadze, N., et al. (2015) · eLife · doi:10.7554/elife.12997 · Cited by 604 · cited 3× · see citing works
“We found that genetic clearance of senescent cells improved adipogenesis in fat tissue in older, naturally-aged mice (20), a finding that was subsequently confirmed by others (39).”
Self-citationFridman, J. S., Scherle, P., Collins, R. J., Burn, T. C., Li, Y., Li, J., Covington, M. B., Thomas, B. A., Collier, P., Favata, M. F., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902819 · Cited by 472 · cited 1× · see citing works
“Other inhibitors that target different JAKs are in clinical trials for treating myelofibrosis (22, 30), acute myeloid leukemia (31), lymphoma (32), and rheumatoid arthritis (22, 33, 34).”
Inhibition of JAK-STAT signaling stimulates adult satellite cell function
Price, F. D., von Maltzahn, J., Bentzinger, C. F., Dumont, N. A., Yin, H., Chang, N. C., Wilson, D. H., Frenette, J., & Rudnicki, M. A. (2014) · Nature Medicine · doi:10.1038/nm.3655 · Cited by 433 · cited 1× · see citing works
“Furthermore, JAK inhibitors have been found to improve antitumor responses by reprogramming the SASP in senescent cells (NVP-BSK805, JAK2 inhibitor) (35), promoting hair growth (ruxolitinib and tofacitinib) (36), and improving muscle stem cell function and muscle regeneration (Tyrphostin AG 490, JAK2 inhibitor) (37).”
Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity
Palmer, A. K., Tchkonia, T., LeBrasseur, N. K., Chini, E. N., Xu, M., & Kirkland, J. L. (2015) · Diabetes · doi:10.2337/db14-1820 · Cited by 423 · see citing works
Self-citationPartial Impairment of Cytokine Responses in Tyk2-Deficient Mice
Karaghiosoff, M., Neubauer, H. J., Lassnig, C., Kovarik, P., Schindler, H., Pircher, H., McCoy, B., Bogdan, C., Decker, T., Brem, G., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)00054-6 · Cited by 422 · cited 1× · see citing works
“TYK2 plays a critical role in immune cell function and host defenses (27, 28).”
Toso, A., Revandkar, A., Di Mitri, D., Guccini, I., Proietti, M., Sarti, M., Pinton, S., Zhang, J., Kalathur, M., Civenni, G., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.044 · Cited by 418 · cited 1× · see citing works
“Furthermore, JAK inhibitors have been found to improve antitumor responses by reprogramming the SASP in senescent cells (NVP-BSK805, JAK2 inhibitor) (35), promoting hair growth (ruxolitinib and tofacitinib) (36), and improving muscle stem cell function and muscle regeneration (Tyrphostin AG 490, JAK2 inhibitor) (37).”
Rapamycin extends murine lifespan but has limited effects on aging
Neff, F., Flores-Dominguez, D., Ryan, D. P., Horsch, M., Schröder, S., Adler, T., Afonso, L. C., Aguilar-Pimentel, J. A., Becker, L., Garrett, L., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67674 · Cited by 374 · cited 1× · see citing works
“It was shown to extend lifespan in mice (43), while it had limited effects on age-related tissue dysfunction (44).”
p16Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion
Helman, A., Klochendler, A., Azazmeh, N., Gabai, Y., Horwitz, E., Anzi, S., Swisa, A., Condiotti, R., Granit, R. Z., Nevo, Y., et al. (2016) · Nature Medicine · doi:10.1038/nm.4054 · Cited by 351 · cited 1× · see citing works
“However, senescent cells appear to be important for several biological processes, including prevention of fibrosis (3), promotion of wound healing (50), and insulin secretion (51).”
Shimoda, K., Kato, K., Aoki, K., Matsuda, T., Miyamoto, A., Shibamori, M., Yamashita, M., Numata, A., Takase, K., Kobayashi, S., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)00055-8 · Cited by 322 · cited 1× · see citing works
“TYK2 plays a critical role in immune cell function and host defenses (27, 28).”
Replicative senescence in normal liver, chronic hepatitis C, and hepatocellular carcinomas
Paradis, V., Youssef, N., Dargère, D., Bâ, N., Bonvoust, F., Deschatrette, J., & Bedossa, P. (2001) · Human Pathology · doi:10.1053/hupa.2001.22747 · Cited by 314 · see citing works
Coppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302 · cited 13× · see citing works
“These SASP components can alter the microenvironment within tissues and affect the function of neighboring cells, which can eventually lead to local and systemic dysfunction.”
InfluentialCellular senescence in vivo: Its relevance in ageing and cardiovascular disease
Erusalimsky, J. D., & Kurz, D. J. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.04.010 · Cited by 252 · see citing works
Pharmacologic inhibition of JAK-STAT signaling promotes hair growth
Harel, S., Higgins, C. A., Cerise, J. E., Dai, Z., Chen, J. C., Clynes, R., & Christiano, A. M. (2015) · Science Advances · doi:10.1126/sciadv.1500973 · Cited by 238 · cited 1× · see citing works
“Furthermore, JAK inhibitors have been found to improve antitumor responses by reprogramming the SASP in senescent cells (NVP-BSK805, JAK2 inhibitor) (35), promoting hair growth (ruxolitinib and tofacitinib) (36), and improving muscle stem cell function and muscle regeneration (Tyrphostin AG 490, JAK2 inhibitor) (37).”
Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis
Pardanani, A. D., Laborde, R. R., Lasho, T. L., Finke, C. M., Begna, K. H., Al‐Kali, A., Hogan, W. J., Litzow, M. R., Leontovich, A. A., Kowalski, M. M., et al. (2013) · Leukemia · doi:10.1038/leu.2013.71 · Cited by 234 · see citing works
Glucocorticoids suppress selected components of the senescence‐associated secretory phenotype
Laberge, R., Zhou, L., Sarantos, M. R., Rodier, F., Freund, A., de Keizer, P. L. J., Liu, S., Demaria, M., Cong, Y., Kapahi, P., et al. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00818.x · Cited by 229 · cited 1× · see citing works
“In addition to JAK inhibitors, other compounds have been noted to suppress SASP components, including metformin (40), rapamycin (41), and glucocorticoids (42).”
Melk, A., Kittikowit, W., Sandhu, I., Halloran, K. M., Grimm, P., Schmidt, B. M. W., & Halloran, P. F. (2003) · Kidney International · doi:10.1046/j.1523-1755.2003.00032.x · Cited by 205 · see citing works
Hart, S., Goh, K. C., Novotny‐Diermayr, V., Hu, C. Y., Hentze, H., Tan, Y., Madan, B., Amalini, C., Loh, Y. K., Ong, L. C., et al. (2011) · Leukemia · doi:10.1038/leu.2011.148 · Cited by 204 · cited 1× · see citing works
“Other inhibitors that target different JAKs are in clinical trials for treating myelofibrosis (22, 30), acute myeloid leukemia (31), lymphoma (32), and rheumatoid arthritis (22, 33, 34).”
Clinical strategies and animal models for developing senolytic agents
Kirkland, J. L., & Tchkonia, T. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2014.10.012 · Cited by 168 · cited 1× · see citing works
“Senolytic drugs offer an alternative option, since it may be feasible to administer them intermittently instead of continuously (49).”
Self-citationMolecular Pathways: Molecular Basis for Sensitivity and Resistance to JAK Kinase Inhibitors
Meyer, S. C., & Levine, R. L. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0279 · Cited by 164 · see citing works
JAK3: a novel JAK kinase associated with terminal differentiation of hematopoietic cells.
Rane, S. G., & Reddy, E. P. (1994) · PubMed · Cited by 149 · see citing works
Cellular Senescence and the Biology of Aging, Disease, and Frailty
LeBrasseur, N. K., Tchkonia, T., & Kirkland, J. L. (2015) · Nestlé Nutrition Institute Workshop Series · doi:10.1159/000382054 · Cited by 147 · see citing works
Self-citationStout, M. B., Tchkonia, T., Pirtskhalava, T., Palmer, A. K., List, E. O., Berryman, D. E., Lubbers, E. R., Escande, C., Spong, A., Masternak, M. M., et al. (2014) · Aging · doi:10.18632/aging.100681 · Cited by 136 · see citing works
Self-citationEmerging roles of JAK–STAT signaling pathways in adipocytes
Richard, A. J., & Stephens, J. M. (2011) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2011.03.007 · Cited by 108 · cited 1× · see citing works
“JAK1 and 2 play essential roles in inflammatory signaling and in regulating growth hormone and other endocrine signals (24).”
Lestaurtinib, a multitargeted tyrosinse kinase inhibitor: from bench to bedside
Shabbir, M., & Stuart, R. K. (2010) · Expert Opinion on Investigational Drugs · doi:10.1517/13543781003598862 · Cited by 85 · cited 1× · see citing works
“Other inhibitors that target different JAKs are in clinical trials for treating myelofibrosis (22, 30), acute myeloid leukemia (31), lymphoma (32), and rheumatoid arthritis (22, 33, 34).”
Flagged first, then by citations
1 of the 52 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Senolytics improve physical function and increase lifespan in old age
Xu, M., Pirtskhalava, T., Farr, J. N., Weigand, B. M., Palmer, A. K., Weivoda, M. M., Inman, C. L., Ogrodnik, M. B., Hachfeld, C. M., Fraser, D. G., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0092-9 · Cited by 2,287 · see citing works
Self-citationCellular senescence: a key therapeutic target in aging and diseases
Zhang, L., Pitcher, L. E., Yousefzadeh, M. J., Niedernhofer, L. J., Robbins, P. D., & Zhu, Y. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158450 · Cited by 631 · see citing works
Interferon target-gene expression and epigenomic signatures in health and disease
Barrat, F. J., Crow, M. K., & Ivashkiv, L. B. (2019) · Nature Immunology · doi:10.1038/s41590-019-0466-2 · Cited by 537 · see citing works
Strategies for targeting senescent cells in human disease
Gasek, N. S., Kuchel, G. A., Kirkland, J. L., & Xu, M. (2021) · Nature Aging · doi:10.1038/s43587-021-00121-8 · Cited by 501 · see citing works
Self-citationRoles of JAK2 in Aging, Inflammation, Hematopoiesis and Malignant Transformation
Perner, F., Perner, C., Ernst, T., & Heidel, F. H. (2019) · Cells · doi:10.3390/cells8080854 · Cited by 247 · see citing works
“In how far kinase inhibition could be utilized as an intervention for age related functional decline or chronic degenerative diseases is currently a subject to controversial discussions within the community [119,120].”
BackgroundTherapeutic interventions for aging: the case of cellular senescence
Soto-Gamez, A., & Demaria, M. (2017) · Drug Discovery Today · doi:10.1016/j.drudis.2017.01.004 · Cited by 192 · see citing works
Reducing Senescent Cell Burden in Aging and Disease
Pignolo, R. J., Passos, J. F., Khosla, S., Tchkonia, T., & Kirkland, J. L. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.03.005 · Cited by 177 · see citing works
“, using INK-ATTAC mice) or pharmacologically with senolytic agents [4, 11, 13, 60].”
MethodSelf-citationAnti-senescence compounds: A potential nutraceutical approach to healthy aging
Gurău, F., Baldoni, S., Prattichizzo, F., Espinosa, E., Amenta, F., Procopio, A. D., Albertini, M. C., Bonafè, M., & Olivieri, F. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.05.001 · Cited by 179 · see citing works
Wang, B., Wang, L., Gasek, N. S., Zhou, Y., Kim, T., Guo, C., Jellison, E. R., Haynes, L., Yadav, S., Tchkonia, T., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00107-6 · Cited by 145 · see citing works
Self-citationImmunosenescence: signaling pathways, diseases and therapeutic targets
Fu, Y., Wang, B., Alu, A., Hong, W., Hong, L., He, X., Shi, H., Cheng, P., & Yang, X. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02371-z · Cited by 157 · see citing works
“34,304 Notably, the JAK pathway is more active in the adipose tissue of aged animals than in that of their younger counterparts.”
Hou, J., Chen, K., He, C., Li, X., Huang, M., Jiang, Y.-Z., Jiao, Y.-R., Xiao, Q., He, W., Liu, L., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00694-0 · Cited by 136 · see citing works
“Senolytics, which are drugs designed to selectively target senescent cells 50 , show promising results in preclinical models and clinical trials 33,51–53 , However, long-term safety and efficacy of senolytics have not been clinically proven.”
Chronic inflammation and sarcopenia: A regenerative cell therapy perspective
Chhetri, J. K., Barreto, P. D. S., Fougère, B., Rolland, Y., Vellas, B. J., & Cesari, M. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2017.12.023 · Cited by 126 · see citing works
The role of epigenetics in renal ageing
Shiels, P. G., McGuinness, D., Eriksson, M., Kooman, J. P., & Stenvinkel, P. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.78 · Cited by 114 · see citing works
Down-syndrome-induced senescence disrupts the nuclear architecture of neural progenitors
Meharena, H. S., Marco, A., Dileep, V., Lockshin, E. R., Akatsu, G. Y., Mullahoo, J., Watson, L. A., Ko, T., Guerin, L. N., Abdurrob, F., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2021.12.002 · Cited by 92 · see citing works
Neutrophil Elastase Inhibitors and Chronic Kidney Disease
Bronze-da-Rocha, E., & Santos‐Silva, A. (2018) · International Journal of Biological Sciences · doi:10.7150/ijbs.26111 · Cited by 93 · see citing works
“The inhibition of Jak/STAT pathway prevents the secretion of inflammatory cytokines, chemokines, proteases and growth factors and might be used to extend longevity in ageing [32].”
BackgroundPotential Regulators of the Senescence-Associated Secretory Phenotype During Senescence and Aging
Han, X., Lei, Q., Xie, J., Liu, H., Li, J., Zhang, X., Zhang, T., & Gou, X. (2022) · The Journals of Gerontology Series A · doi:10.1093/gerona/glac097 · Cited by 96 · see citing works
The JAK1/2 inhibitor ruxolitinib delays premature aging phenotypes
Griveau, A., Wiel, C., Ziegler, D. V., Bergö, M. O., & Bernard, D. (2020) · Aging Cell · doi:10.1111/acel.13122 · Cited by 78 · see citing works
“Overall, these results confirm that JAK1/2 inhibition by ruxolitinib impacts not only the secretome of senescent cells, as already suggested by others (Farr et al., 2017; Xu et al., 2015, 2016), but also the cell cycle arrest, which can itself be induced by the SASP (Acosta et al., 2008).”
BackgroundInfluentialMatar, D. B., Zhra, M., Nassar, W. K., Altemyatt, H., Naureen, A., Abotouk, N., Elahi, M. A., & Aljada, A. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1592683 · Cited by 80 · see citing works
“SASP encompasses secretion of diverse factors - in fl ammatory mediators, growth factors, and matrix components (418) - regulated through NF-k B, C/EBP b , and Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling networks (419, 420).”
Advancements in therapeutic drugs targeting of senescence
Zhu, M., Meng, P., Ling, X., & Zhou, L. (2020) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622320964125 · Cited by 68 · see citing works
Fang, C., Liu, B., & Wan, M. (2023) · Calcified Tissue International · doi:10.1007/s00223-023-01100-4 · Cited by 69 · see citing works
“The JAK/STAT pathway is more highly activated in senescent than non-senescent cells [213].”
BackgroundVascular senescence and aging: mechanisms, clinical implications, and therapeutic prospects
Picos, A., Seoane, N., Campos‐Toimil, M., & Viña, D. (2025) · Biogerontology · doi:10.1007/s10522-025-10256-5 · Cited by 81 · see citing works
“Other senomorphics, like JAK inhibitors, target cytokine signaling cascades to diminish the pro-inflammatory environment created by senescent cells (Valenzuela 2022; Xu et al. 2016; Xu et al. 2015).”
Ali, D., Figeac, F., Caci, A., Ditzel, N., Schmal, C., Kerckhofs, G., Havelund, J. F., Færgeman, N. J., Rauch, A., Tencerová, M., et al. (2022) · Aging Cell · doi:10.1111/acel.13726 · Cited by 65 · see citing works
Accelerated Vascular Aging in Chronic Kidney Disease: The Potential for Novel Therapies
Hobson, S., Arefin, S., Witasp, A., Hernandez, L. N., Kublickiene, K. R., Shiels, P. G., & Stenvinkel, P. (2023) · Circulation Research · doi:10.1161/circresaha.122.321751 · Cited by 64 · see citing works
Adipose tissue aging is regulated by an altered immune system
Zhang, Y.-X., Ou, M.-Y., Yang, Z.-H., Sun, Y., Li, Q.-F., & Zhou, S.-B. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1125395 · Cited by 62 · see citing works
Cellular Senescence Affects Cardiac Regeneration and Repair in Ischemic Heart Disease
Yan, C., Xu, Z.-M., & Huang, W. (2021) · Aging and Disease · doi:10.14336/ad.2020.0811 · Cited by 60 · see citing works
Cellular Senescence and Periodontitis: Mechanisms and Therapeutics
Chen, S., Zhou, D., Liu, O., Chen, H., Wang, Y., & Zhou, Y. (2022) · Biology · doi:10.3390/biology11101419 · Cited by 49 · see citing works
A tale of the good and bad: Cell senescence in bone homeostasis and disease
Liu, X., & Wan, M. (2019) · International review of cytology · doi:10.1016/bs.ircmb.2019.03.005 · Cited by 44 · see citing works
Lourido, F., Quenti, D., Salgado-Canales, D., & Tobar, N. (2021) · Scientific Reports · doi:10.1038/s41598-021-82944-4 · Cited by 46 · see citing works
Su, X., Shen, Y., Jin, Y., Kim, I., Weintraub, N. L., & Tang, Y. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.654316 · Cited by 45 · see citing works
Exosomes and Micro-RNAs in Aging Process
Hamdan, Y., Mazini, L., & Malka, G. (2021) · Biomedicines · doi:10.3390/biomedicines9080968 · Cited by 43 · see citing works
Cellular senescence as a therapeutic target to improve renal transplantation outcome
van Willigenburg, H., de Keizer, P. L. J., & de Bruin, R. W. F. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.02.015 · Cited by 38 · see citing works
“Unfortunately, also long term treatment with these compounds has deleterious effects as they can result in anemia and thrombocytopenia in humans [81].”
Pro‐inflammatory cytokines mediating senescence of vascular endothelial cells in atherosclerosis
Shang, D., Liu, H., & Tu, Z. (2023) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12915 · Cited by 37 · see citing works
Senotherapy: growing old and staying young?
Schmitt, R. (2017) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-1972-4 · Cited by 35 · see citing works
“Another senescence-associated pathway that might be an interesting target is the JAK/STAT pathway, which is more highly activated in senescent than in non-senescent cells [63].”
BackgroundPast and Future Directions for Research on Cellular SenescencePreprint
Zhu, Y. Z., Anastasiadis, Z. P., Espíndola‐Netto, J. M., Evans, T. S., Tchkonia, T., & Kirkland, J. L. (2023) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041205 · Cited by 36 · see citing works
Self-citationMechanotransduction for therapeutic approaches: Cellular aging and rejuvenation
Han, H.-M., Kim, S.-Y., & Kim, D. (2025) · APL Bioengineering · doi:10.1063/5.0263236 · Cited by 29 · see citing works
“178 This increased activation is associated with increased inflammation and metabolic dysfunction, indicating a direct link between JAK/STAT signaling and aging.”
Sahu, P., & Satapathy, T. (2025) · Inflammopharmacology · doi:10.1007/s10787-025-01867-y · Cited by 29 · see citing works
“For instance, rapamycin dampens SASP output by inhibiting mTOR signaling, while JAK inhibitors curb the autocrine and paracrine cytokine loops that amplify SASP (Xu et al. 2016).”
Gao, L., Zheng, W.-G., Wu, X., Du, G., & Qin, X. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00024 · Cited by 27 · see citing works
Understanding cellular senescence: pathways involved, therapeutics and longevity aiding
Kumar, A., & Thirumurugan, K. (2023) · Cell Cycle · doi:10.1080/15384101.2023.2287929 · Cited by 26 · see citing works
“Senomorphic compounds act on suppressing the SASP signaling, while senolytic compounds help in clearing senescent cells [74,201].”
BackgroundCirculating microRNA profile in humans and mice with congenital GH deficiency
Saccon, T. D., Schneider, A., Marinho, C. G., Nunes, A., Noureddine, S. A., Dhahbi, J. M., López, Y. O. N., LeMunyan, G., Salvatori, R., Oliveira, C. R. P., et al. (2021) · Aging Cell · doi:10.1111/acel.13420 · Cited by 24 · see citing works
“Recent evidence suggests the JAK/STAT pathway is more active in senescent cells and that its inhibition can alleviate age- related tissue dysfunction (Xu et al., 2016).”
BackgroundExtracellular Vesicles and Hematopoietic Stem Cell Aging
Goldberg, L. R. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.314643 · Cited by 20 · see citing works
Combining stem cell rejuvenation and senescence targeting to synergistically extend lifespan
Kaur, P., Otgonbaatar, A., Ramamoorthy, A., Chua, E. H. Z., Harmston, N., Gruber, J., & Tolwinski, N. S. (2022) · Aging · doi:10.18632/aging.204347 · Cited by 20 · see citing works
“injury leading to asymmetric divisions and lower numbers of stem cells (48, 49).”
BackgroundSenolytic therapies for cardiovascular aging: tackling fibrosis and metabolic dysfunction
Atlante, S., Zamperla, M. G., Cis, L., Farsetti, A., & Gaetano, C. (2025) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2025.07.009 · Cited by 19 · see citing works
Yin, F., He, Y., Li, J., & Gao, Y. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1596686 · Cited by 16 · see citing works
Zhu, J., Huang, Y., Lei, L., Zhao, Z., Wang, H., Li, Z., Liu, H., Wang, J., & Zheng, Z. (2025) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2025.02.773 · Cited by 15 · see citing works
Ding, F., Yu, Y., Zhao, J., Wei, S.-B., Zhang, Y., Han, J.-H., Li, Z., Jiang, H.-B., Ryu, D., Cho, M., et al. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1593096 · Cited by 14 · see citing works
“Notable examples include Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway inhibitors, rapamycin, and metformin–all of which have been found to dampen SASP signaling (Xu et al., 2016).”
Cellular Senescence and Immunosenescence in Melanoma: Insights From the Tumor Microenvironment
Xiong, L., & Cheng, J. (2025) · Cancer Medicine · doi:10.1002/cam4.71223 · Cited by 16 · see citing works
“Agents such as rapamycin, metformin, or JAK inhibitors have been shown to blunt SASP production in tumor or stromal compartments, reducing chronic inflammation and myeloid cell recruitment [120, 121].”
Xu, M., Xia, Z.-Y., Sun, J., Liu, C., An, Y., Xu, J., Zhang, S.-H., Zhong, X., Zeng, N., Ma, S., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1395047 · Cited by 14 · see citing works
Self-citationWu, J., Liu, X., Liu, Y., Su, W., & Zhuo, Y. (2025) · Bioengineering · doi:10.3390/bioengineering12060563 · Cited by 13 · see citing works
Senescent Cells: Dual Implications on the Retinal Vascular System
Habibi-Kavashkohie, M. R., Scorza, T., & Oubaha, M. (2023) · Cells · doi:10.3390/cells12192341 · Cited by 12 · see citing works
“The JAK family is composed of four members (including JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2)) that act through downstream STAT proteins (including Stats 1–4, Stat5a, Stat5b, and Stat6) [91].”
BackgroundInfluentialToma, G. A., Lemnian, I., Karapetian, E., Große, I., & Seliger, B. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.806906 · Cited by 12 · see citing works
“In contrast to these observations, several studies demonstrated that this pathway was defective in old individuals (54, 72), but a comparison of the expression of this pathway in memory CD8 T cells of young versus old donors was not performed in these studies.”
ResultSenomorphic effect of diphenyleneiodonium through AMPK/MFF/DRP1 mediated mitochondrial fission
Liao, K.-M., Chen, C., Luo, W., Hsu, C.-W., Yu, S., Yang, P., & Su, K. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114616 · Cited by 11 · see citing works
Increased vascular smooth muscle cell senescence in aneurysmal Fibulin-4 mutant mice
Stefens, S. J. M., van Vliet, N., IJpma, A. S., Burger, J. E., Li, Y., van Heijningen, P. M., Lindeman, J. H. N., Majoor‐Krakauer, D. F., Verhagen, H. J. M., Kanaar, R., et al. (2024) · npj Aging · doi:10.1038/s41514-024-00154-4 · Cited by 10 · see citing works
“The JAK/STAT signaling pathway is activated in senescent cells and inhibition of this pathway has been shown to suppress SASP secretion and attenuate senescence 25,54 .”
Spina, J. S., Carr, T. L., Phillips, L. A., Knight, H., Crosbie, N. E., Lloyd, S. M., Jhala, M. A., Lam, T. J., Kármán, J., Clements, M. E., et al. (2024) · Aging · doi:10.18632/aging.205994 · Cited by 11 · see citing works
The emerging role of cellular senescence in complications of COVID-19
Mohiuddin, M., & Kasahara, K. (2021) · Cancer Treatment and Research Communications · doi:10.1016/j.ctarc.2021.100399 · Cited by 11 · see citing works
“• The JAK pathway is more activated in senescent cells than in nonsenescent cells [50].”
Alexa‐Stratulat, T., Tanasa, M. P., Cianga, V. A., & Antoniu, S. A. (2022) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2022.2139242 · Cited by 11 · see citing works
Эрдман, В. В., Насибуллин, Т. Р., Tuktarova, I. A., Сомова, Р. Ш., & Mustafina, O. E. (2019) · Russian Journal of Genetics · doi:10.1134/s1022795419050077 · Cited by 10 · see citing works
Key Age-Imposed Signaling Changes That Are Responsible for the Decline of Stem Cell Function
Mehdipour, M., Liu, Y., Liu, C., Kumar, B., Kim, D., Gathwala, R., & Conboy, I. M. (2018) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-2835-0_5 · Cited by 8 · see citing works
Cell Senescence in Heterotopic Ossification
Pignolo, R. J., Kaplan, F. S., & Wang, H. (2024) · Biomolecules · doi:10.3390/biom14040485 · Cited by 7 · see citing works
“The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is overactive in senescent cells, and its inhibition suppresses and partially normalizes the SASP [60].”
Effects of unpaired 1 gene overexpression on the lifespan of Drosophila melanogaster
Moskalev, A., Николаевна, П. Е., Zhavoronkov, A. A., & Shaposhnikov, M. V. (2019) · BMC Systems Biology · doi:10.1186/s12918-019-0687-x · Cited by 7 · see citing works
Dotou, M., L’honoré, A., Moumné, R., & Amri, C. E. (2024) · Journal of Natural Products · doi:10.1021/acs.jnatprod.3c01195 · Cited by 8 · see citing works
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 · see citing works
Véret, D., & Brondello, J. (2020) · médecine/sciences · doi:10.1051/medsci/2020220 · Cited by 5 · see citing works
Aging modulation of the immune system and immunotherapy efficacy in cancer
Wang, Y., Liang, M., Mao, Y., Zhu, W., Shen, X., & Guan, W. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1781885 · Cited by 4 · see citing works
“Chronic activation of the JAK-STAT pathway drives cytokine storms, causes hematopoietic stem cell (HSC) dysfunction, and leads to T cell reduction (111, 112).”
Tang, X., Hu, J., Fan, X., Su, H., Li, M., Zhang, L., & Ma, D. (2025) · Immunity & Ageing · doi:10.1186/s12979-025-00541-9 · Cited by 4 · see citing works
“Suppressing SASP can mitigate inflammation and alleviate senescence-related tissue dysfunction [100].”
Tissue-specific biological aging predicts progression in prostate cancer and acute myeloid leukemia
Ramakrishnan, A., Datta, I., Panja, S., Patel, H., Liu, Y., Craige, M. W., Chu, C., Jean-Marie, G., Oladoja, A.-R., Kim, I., et al. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1222168 · Cited by 3 · see citing works
Jia, G., Li, J., Khan, A., Kaushik, A. C., Wu, D., Chen, H., Li, R., Wang, J., Zhang, C., Farooq, A., et al. (2025) · Chemical Biology & Drug Design · doi:10.1111/cbdd.70214 · Cited by 2 · see citing works
“Under senescent conditions, JAK/STAT (Figure S1b) pathway becomes highly activated, which facilitates the progression of aging without reducing SASP levels (Xu et al. 2016).”
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 · see citing works
“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.”
Senomorphic, senolytic, and rejuvenation therapies
Zhu, X. Y., & Lerman, L. O. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-823318-4.00025-1 · Cited by 2 · see citing works
Protein kinase modulation for anti-aging intervention
Muñoz, M. F., Argüelles, S., Ayala, A., & Marotta, F. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-823679-6.00011-4 · Cited by 1 · see citing works
Epigenetic Mechanisms, Assessment and Therapeutics of Epidermal Stem Cells in Skin Aging
Yang, J., Xu, M., Duan, Y., Yuan, Y., Zhang, J., & Jiang, W. (2025) · Stem Cells International · doi:10.1155/sci/7575250 · Cited by 1 · see citing works
“This potential is, however, undermined by fl awed integrins that prevent the cells from securing the fi rm adhesion needed for effective migration [28 – 30].”
Self-citationWei, Z., Li, Z., & Quan, N. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1702207 · Cited by 1 · see citing works
“Studies have shown that SASP inhibition via the JAK/STAT pathway can reduce inflammation (Griveau et al., 2020; Wu et al., 2020) and restore insulin sensitivity (Xu et al., 2016).”
Manni, E., Al‐kuraishy, H. M., Fawzy, M. N., & Batiha, G. E. (2026) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-026-05416-4 · Cited by 1 · see citing works
Brain Aging and Cellular Senescence Trigger Neuroimmunological Dysregulation and Neurodegeneration
Vega-García, A., Apolinar, L. M., Feria-Romero, I. A., Campos‐Bedolla, P., Alberto, G.-G. C., Luna‐Munguía, H., Sofía, R.-H., & Orozco-Suárez, S. A. (2026) · Brain Sciences · doi:10.3390/brainsci16101019 · Cited by 1 · see citing works
“An increase in the β 2-microglobulin component of the major histocompatibility complex (MHC-I) in plasma has been reported, leading to a pro-inflammatory monocyte phenotype linked to cognitive decline and impaired tissue regeneration in the adult brain [129,130].”
A geroscience approach for osteosarcopenia: Autophagy and senescence as therapeutic targets
Cordero, N. P., Schoenlein, P. V., Fulzele, S., & Hill, W. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-820088-9.00031-7 · Cited by 1 · see citing works
Chronobiological Aspects of Aging, Neurodegeneration, and Inflammation
Banerjee, S., Das, S., Halder, N., Bisht, S., Talukdar, A., & Ray, S. (2024) · Progress in inflammation research · doi:10.1007/978-3-031-74744-1_8 · Cited by 1 · see citing works
Sakellaropoulos, T., Binenbaum, I., Lefaki, M., Chatziioannou, A. A., Chondrogianni, N., & Alexopoulos, L. G. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/389692 · Cited by 1 · see citing works
Binenbaum, I., Lefaki, M., Chondrogianni, N., & Chatziioannou, A. A. (2020) · Biogerontology · doi:10.1007/s10522-020-09866-y
Senotherapeutics: Experimental therapy of cellular senescence
Justice, J. N., Niedernhofer, L. J., & Orr, M. E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-815962-0.00012-3
Mason, R. S. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733607913.793560955
She, J., & Wang, C.-Y. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733607913.793549270
Quiescencia y senescencia: enfoque traslacional al paciente oncológico y críticamente enfermo.
Moscoso, S. X. A., Montalvo-Villagómez, M., González, F. E. J., Páez, P. A. V., Montero, C. G. V., & Vélez-Páez, J. L. (2019) · Revista Ecuatoriana de Ciencia Tecnología e Innovación en Salud Pública · doi:10.31790/inspilip.v4i1.154
The current report on drug development focuses on “The new dimension” of cancer hallmarks
Ucche, S., Larasati, Y. A., Maharani, D., Widyardhita, M. H., Widayanti, W. R., & Hermawan, A. (2025) · Gene · doi:10.1016/j.gene.2025.149750
Graft versus host disease treatment and prevention in older adults: A single-database review
Ciurylo, W. A., Hamparsumian, A., Wall, S. A., & Meyers, G. (2026) · Journal of Geriatric Oncology · doi:10.1016/j.jgo.2026.102848
Larsen, E. C., Moon, J. E., King, O. D., & Lawrence, J. B. (2026) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2026.02.014
“…defects in DS. 115 Similarly, GADD45 and the JAK-STAT pathway both relate to cellular senescence, which is known to be increased in DS, 113,114,116,117 and JAK-STAT itself has been reported to be disrupted in DS. 118–120 While these connections to RWDD2B are speculative at this point, we believe…”
Anti-aging Concepts: Adipose Tissue as a Therapeutic Target in Anti-aging Medicine
Knoedler, S., & Prantl, L. (2026) · Springer eBooks · doi:10.1007/978-3-032-01711-6_17
Senescent fibroblasts in aging and pulmonary fibrosis
Palega, S., Borengasser, A. Y., & Sanders, Y. Y. (2026) · Frontiers in Aging · doi:10.3389/fragi.2026.1816071
“…and oxidative stress pathways (Zhang L. et al., 2023). mTOR and JAK inhibitors are particularly relevant for fibroblasts, as they target key signaling nodes that sustain the profibrotic SASP (Xu et al., 2014; Carroll et al., 2017; Xu et al., 2015; Laberge et al., 2015; Xu et al., 2016).”
Targeting the JAK-STAT signaling pathway ameliorates chemotherapy-induced skin aging
Li, J., Luo, Z., Zheng, Y., Wang, J., Cai, R., Chen, L., Shi, D., Zhang, D., Li, L., Chen, C., et al. (2026) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2026.117946
Paul, B. M., Kannan, G., Arunachalam, K., & Thangaraj, P. (2026) · Inflammopharmacology · doi:10.1007/s10787-026-02346-8
“Similarly, Tofacitinib, an FDA-approved JAK inhibitor used for autoimmune disorders, has emerged as an additional candidate for targeting cytokine-amplifying senescence networks (Gurău et al. 2018; Xu et al. 2016).”
Wang, Y., Huang, Z., Tseng, Y., Ma, H., Chen, K., Pan, X., Ye, H., Cheng, T., Ge, J., Deng, J., et al. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-08705-x
“Within this family, JAK1 and JAK2 are particularly crucial for transducing inflammatory and other endocrine signals [25].”
Future perspectives: personalized medicine and senescence modulation in cardiovascular health
Nissar, I., Uppal, J., Gayaz, M., Chawla, A., Mohi-ud-din, R., Hussain, M. S., Mir, R. H., & Ahmad, A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-45811-8.00008-8
Purkayastha, K., Roy, A., Bhattacharya, P., & Borah, A. (2026) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2026.130989
Garnier, N., Ossi, J., Marconi, V. C., Schinazi, R. F., & Titanji, B. K. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1887876
“Senescent cells secrete a wide range of pro-in fl ammatory cytokines, chemokines, and growth factors which de fi ne senescence-associated secretory phenotype (SASP) (69).”
InfluentialImmunosenescence in uveitis: From mechanistic insights to therapeutic implications
Wu, Y., Zou, Y., Yang, M., Gu, W., Ye, Z., Deng, J., Ohno‐Matsui, K., & Kamoi, K. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103381
Jiang, S., Xiao, D., Chen, Y., Kuang, Y., Xian-Gan, C. H. E. N., Li, Z., Zhang, C., & Li, J. (2026) · Research Square · doi:10.21203/rs.3.rs-10879351/v1
Guan, X., Lu, M., Cui, X., Zhang, D., Lei, Z., Lin, L., Li, Y., Hu, Y., & Li, C. (2026) · Advanced Science · doi:10.1002/advs.77891
“They propagate senescence to surrounding non-senescent cells through SASP [ 9 ].”
Wang, J., Liu, R., Zhang, X., Qi, G., Xu, Q., & Jia, F. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103412
Huang, D., Si, H., Jiao, X., Xuan, S., Yang, T., Ba, M., Qi, D., Pei, X., 卢丁丽, 黄深振, et al. (2026) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.67.12.73
“86,87 Multi-lineage activation of the JAK–STAT pathway supports its consideration as a broad-spectrum anti-inflammatory target, 88,89 whereas PD-L1 upregulation suggests the potential utility of immune checkpoint modulation.”
- Authors
- Xu, M., Tchkonia, T., & Kirkland, J. L.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Kirkland, James L.
- Venue
- Pharmacological Research
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 111
- Pages
- 152-154
- ISSN
- 1043-6618 (ISSN-L)
- PMC
- PMC5026572
- OpenAlex
- W2403936349
- Cited by
- 99
- References
- 52
- Citations by year
- 2026: 20 · 2025: 15 · 2024: 8 · 2023: 11 · 2022: 9 · 2021: 12 · 2020: 5 · 2019: 7 · 2018: 9 · 2017: 3
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pharmacological Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (AG013925, AG044396, AG19899)
- Robert and Arlene Kogod Center on Aging
- Connor Group
- Ted Nash Foundation
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- JAK/STAT signaling, cellular senescence, senescence-associated secretory phenotype, aging, JAK inhibition, healthspan, senolytics, inflammatory cytokines, tissue microenvironment
- MeSH terms
- Frailty, Janus Kinase Inhibitors, Age Factors, Aged, Aged, 80 and over, Aging, Animals, Humans, Phenotype, Drug Design, Signal Transduction, Frail Elderly, Cellular Senescence, Cell Proliferation, STAT Transcription Factors, Janus Kinases, Molecular Targeted Therapy, Cellular Microenvironment
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