The DOI matches its Crossref record; 44 of the 45 references it cites were found in a registry or an index.
Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH
Open accessAbstract
Ageing is a result of gradual and overall functional deteriorations across the body; however, it is unknown whether an individual tissue primarily works to mediate the ageing progress and control lifespan. Here we show that the hypothalamus is important for the development of whole-body ageing in mice, and that the underlying basis involves hypothalamic immunity mediated by IκB kinase-β (IKK-β), nuclear factor κB (NF-κB) and related microglia-neuron immune crosstalk. Several interventional models were developed showing that ageing retardation and lifespan extension are achieved in mice by preventing ageing-related hypothalamic or brain IKK-β and NF-κB activation. Mechanistic studies further revealed that IKK-β and NF-κB inhibit gonadotropin-releasing hormone (GnRH) to mediate ageing-related hypothalamic GnRH decline, and GnRH treatment amends ageing-impaired neurogenesis and decelerates ageing. In conclusion, the hypothalamus has a programmatic role in ageing development via immune-neuroendocrine integration, and immune inhibition or GnRH restoration in the hypothalamus/brain represent two potential strategies for optimizing lifespan and combating ageing-related health problems.
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
“inflammatory and stress responses activate NF-κB in the hypothalamus and induce a signaling pathway that results in reduced production of gonadotropin-releasing hormone (GnRH) by neurons”
From The Hallmarks of Aging (2013) · cites this paper as Zhang et al., 2013
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
“This GnRH decline can contribute to numerous aging-related changes such as bone fragility, muscle weakness, skin atrophy and reduced neurogenesis.”
From The Hallmarks of Aging (2013) · cites this paper as Zhang et al., 2013
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“GnRH treatment prevents aging-impaired neurogenesis and decelerates aging development in mice”
From The Hallmarks of Aging (2013) · cites this paper as Zhang et al., 2013
In the citing paper
“Gonadotropin-releasing hormone ameliorates neurogenesis and decelerates the ageing process in mice.463”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [463]
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
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
Mechanisms underlying inflammation in neurodegeneration
Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., & Gage, F. H. (2010) · Cell · doi:10.1016/j.cell.2010.02.016 · Cited by 3,580
Pathways towards and Away from Alzheimer’s Disease
Mattson, M. P. (2004) · Nature · doi:10.1038/nature02621 · Cited by 3,052
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208
The ageing systemic milieu negatively regulates neurogenesis and cognitive function
Villeda, S. A., Luo, J., Mosher, K. I., Zou, B., Britschgi, M., Bieri, G., Stan, T. M., Fainberg, N., Ding, Z., Eggel, A., et al. (2011) · Nature · doi:10.1038/nature10357 · Cited by 1,763
Hypothalamic IKKβ/NF-κB and ER Stress Link Overnutrition to Energy Imbalance and Obesity
Zhang, X., Zhang, G., Zhang, H., Karin, M., Bai, H., & Cai, D. (2008) · Cell · doi:10.1016/j.cell.2008.07.043 · Cited by 1,350
Self-citationSIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin
Michishita, E., McCord, R. A., Berber, E., Kioi, M., Padilla-Nash, H., Damian, M., Cheung, P., Kusumoto, R., Kawahara, T. L. A., Barrett, J. C., et al. (2008) · Nature · doi:10.1038/nature06736 · Cited by 1,111
Microglial cell origin and phenotypes in health and disease
Saijo, K., & Glass, C. K. (2011) · Nature Reviews Immunology · doi:10.1038/nri3086 · Cited by 1,100
Kawahara, T. L. A., Michishita, E., Adler, A. S., Damian, M., Berber, E., Lin, M., McCord, R. A., Ongaigui, K. C. L., Boxer, L. D., Chang, H. Y., et al. (2009) · Cell · doi:10.1016/j.cell.2008.10.052 · Cited by 1,090
Saijo, K., Winner, B., Carson, C. T., Collier, J. G., Boyer, L., Rosenfeld, M. G., Gage, F. H., & Glass, C. K. (2009) · Cell · doi:10.1016/j.cell.2009.01.038 · Cited by 957
Cited by
Sorted by citations
Items 501–600 of 835
Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon
Zambusi, A., Burhan, Ö. P., Giaimo, R. D., Schmid, B., & Ninkovic, J. (2020) · Cells · doi:10.3390/cells9020350 · Cited by 17
Mao, C.-C., & Cai, X. (2020) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x15666200422103916 · Cited by 16
Ogawa, S., & Parhar, I. S. (2021) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2021.100963 · Cited by 15
Perspective: Neuroregenerative Nutrition
Steindler, D. A., & Reynolds, B. A. (2017) · Advances in Nutrition · doi:10.3945/an.117.015388 · Cited by 18
Yuan, F., Yin, H., Deng, Y., Jiao, F., Jiang, H., Niu, Y., Chen, S., Ying, H., Zhai, Q., Chen, Y., et al. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101084 · Cited by 15
Adams, J. M., Rege, S. V., Liu, A. T., Vu, N. V., Raina, S., Kirsher, D. Y., Nguyen, A. L., Harish, R., Szoke, B. G., Leone, D. P., et al. (2023) · Science Advances · doi:10.1126/sciadv.adf8764 · Cited by 16
“Inflammaging in the periphery ( 13 , 14 ) and within the brain ( 15 – 17 ) is detectable before the onset of disease symptoms, and failure to resolve this chronic inflammation has been hypothesized to be a major contributor to aging-related cognitive decline.”
The Quest for Eternal Youth: Hallmarks of Aging and Rejuvenating Therapeutic Strategies
Nunkoo, V. S., Cristian, A., Jurcău, A., Diaconu, R. G., & Jurcău, M. C. (2024) · Biomedicines · doi:10.3390/biomedicines12112540 · Cited by 15
Cortés‐Campos, C., Letelier, J., Ceriani, R., & Whitlock, K. E. (2015) · Biology Open · doi:10.1242/bio.010447 · Cited by 14
“, 2003), and the recently proposed role for hypothalamic GnRH in the recuperation of ageing-impaired neurogenesis (Zhang et al., 2013).”
BackgroundResultThe Role of Aging in Alzheimer’s Disease
Kerchner, G. A., & Wyss‐Coray, T. (2015) · Springer eBooks · doi:10.1007/978-3-319-23246-1_7 · Cited by 14
He, X.-Q., Tian, Y., Lei, L., Zhi, Q., Zhao, J., & Ming, J. (2020) · Journal of Functional Foods · doi:10.1016/j.jff.2020.104089 · Cited by 15
Saccà, S. C., Vernazza, S., Iorio, E. L., Tirendi, S., Bassi, A. M., Gandolfi, S., & Izzotti, A. (2020) · Progress in brain research · doi:10.1016/bs.pbr.2020.06.003 · Cited by 14
Effects of long-term resveratrol treatment in hypothalamic astrocyte cultures from aged rats
Sovrani, V., Bobermin, L. D., Santos, C. L., Brondani, M., Gonçalves, C., Leipnitz, G., & Quincozes‐Santos, A. (2022) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-022-04585-z · Cited by 15
Growth hormone actions during development influence adult phenotype and longevity
Bartke, A., Sun, L. Y., Fang, Y., & Hill, C. M. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2015.12.011 · Cited by 14
Reece, A. S., Thomas, M., Norman, A. F., & Hulse, G. K. (2016) · Reproductive Toxicology · doi:10.1016/j.reprotox.2016.09.006 · Cited by 14
Bonasera, S. J., Arikkath, J., Boska, M. D., Chaudoin, T. R., DeKorver, N. W., Goulding, E. H., Hoke, T. A., Mojtahedzedah, V., Reyelts, C. D., Sajja, B. R., et al. (2016) · Aging · doi:10.18632/aging.101040 · Cited by 14
“support of this concept, interventions inhibiting hypothalamic IKKβ or NFκB activity in aged animals ameliorate age-related feeding phenotypes [46].”
BackgroundAlé, A., Zhang, Y., Han, C., & Cai, D. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00337.2016 · Cited by 14
Self-citationLifespan regulation in α/β posterior neurons of the fly mushroom bodies by Rab27
Lien, W., Chen, Y., Li, Y., Wu, J., Huang, K., Lin, J., Lin, S., Hou, C., Wang, H., Wu, C., et al. (2020) · Aging Cell · doi:10.1111/acel.13179 · Cited by 13
“Several recent studies suggest that the hypothalamus plays a pivotal role in longevity and it may be a regulator of systemic aging (Zhang et al., 2013; Zhao et al., 2017).”
BackgroundBeyond Host Defense: Deregulation of Drosophila Immunity and Age-Dependent Neurodegeneration
Arora, S., & Ligoxygakis, P. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01574 · Cited by 14
“The hypothalamus the neuroendocrine functional center of the body is also responsible for systemic aging though NF-κB signaling (25) and thus provide a potential therapeutic approach to combat age and age related disorders (68).”
BackgroundAPOE and MS4A6A interact with GnRH signaling in Alzheimer's disease: Enrichment of epistatic effects
Cáceres, A., Vargas, J. E., & González, J. R. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.05.009 · Cited by 14
Tumor-derived cyclooxygenase-2 fuels hypothalamic inflammation
Li, X., Zhu, X., Diba, P., Shi, X., Vrieling, F., Jansen, F. A. C., Balvers, M. G. J., de Bus, I., Levasseur, P. R., Sattler, A. L., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.11.002 · Cited by 13
Lee, J., Xue, X., Au, E., McIntyre, W. B., Asgariroozbehani, R., Panganiban, K. J., Tseng, G. C., Papoulias, M., Smith, E., Monteiro, J., et al. (2024) · Translational Psychiatry · doi:10.1038/s41398-023-02716-8 · Cited by 13
Meyer, K., & Yankner, B. A. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.09.012 · Cited by 13
“Cai and colleagues recently offered a proof of principle by demonstrating a link between systemic aging and inflammation and hormone secretion in the hypothalamus (Zhang et al., 2013).”
BackgroundSugiura, A., Shimizu, T., Kameyama, T., Maruo, T., Kedashiro, S., Miyata, M., Mizutani, K., & Takai, Y. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.609911 · Cited by 13
Spindler, M., & Thiel, C. M. (2022) · GeroScience · doi:10.1007/s11357-022-00630-3 · Cited by 14
Effects of neuroleptics administration on adult neurogenesis in the rat hypothalamus
Rojczyk, E., Pałasz, A., & Wiaderkiewicz, R. (2015) · Pharmacological Reports · doi:10.1016/j.pharep.2015.04.014 · Cited by 13
Wang, Z., Khor, S., & Cai, D. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.005429 · Cited by 13
Self-citationDoes Calorie Restriction Modulate Inflammaging via FoxO Transcription Factors?
Kim, S. E., Mori, R., & Shimokawa, I. (2020) · Nutrients · doi:10.3390/nu12071959 · Cited by 14
CanToxoplasma gondiiPave the Road for Dementia?
Saftawy, E. A. E., Amin, N. M. A., Sabry, R. M., El‐Anwar, N., Shash, R. Y., Elsebaie, E. H., & Wassef, R. M. (2020) · Journal of Parasitology Research · doi:10.1155/2020/8859857 · Cited by 13
Gonadotropin Releasing Hormone (GnRH) Triggers Neurogenesis in the Hypothalamus of Adult Zebrafish
Ceriani, R., & Whitlock, K. E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115926 · Cited by 13
“The potential role of GnRH in hypothalamic neurogenesis is apparent in the aging process, where the loss of GnRH function is correlated with decreased neurogenesis [27,28].”
BackgroundEpigenetic mechanisms in Alzheimer's disease
Balázs, R. (2014) · Degenerative Neurological and Neuromuscular Disease · doi:10.2147/dnnd.s37341 · Cited by 15
Sharif, A., Ojeda, S. R., & Prévot, V. (2014) · Stem cell biology and regenerative medicine · doi:10.1007/978-1-4899-7399-3_6 · Cited by 13
Tarbali, S., Mehrian, S. K., & Khezri, S. (2022) · Toxicology Mechanisms and Methods · doi:10.1080/15376516.2022.2049412 · Cited by 12
Weinman, M. A., Fischer, J. A., Jacobs, D. C., Goodall, C. P., Bracha, S., & Chappell, P. E. (2019) · BMC Cancer · doi:10.1186/s12885-019-5363-4 · Cited by 12
Zhang, P., Zhai, Y., Cregg, J. M., Ang, K. K. H., Arkin, M. R., & Kenyon, C. J. (2019) · G3 Genes Genomes Genetics · doi:10.1534/g3.119.400618 · Cited by 12
“Recently, it was shown that blocking age-related hypothalamic NF-kB activation could retard aging and extend lifespan of mice (Zhang et al. 2013), thus potentially highlighting a role of chronic inflammation in aging (Salminen et al. 2008; Jenny 2012).”
BackgroundInfluentialDLG2 variants in patients with pubertal disorders
Jee, Y. H., Won, S., Lui, J. C. K., Jennings, M. S., Whalen, P. E., Yue, S., Temnycky, A. G., Barnes, K. M., Cheetham, T. D., Boden, M. G., et al. (2020) · Genetics in Medicine · doi:10.1038/s41436-020-0803-8 · Cited by 12
Enhancing mask activity in dopaminergic neurons extends lifespan in flies
Tian, X. (2021) · Aging Cell · doi:10.1111/acel.13493 · Cited by 12
Sirtuins, Healthspan, and Longevity in Mammals
Giblin, W., & Lombard, D. B. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-411596-5.00003-4 · Cited by 12
Hypothalamic SLC7A14 accounts for aging-reduced lipolysis in white adipose tissue of male mice
Jiang, X., liu, K., Luo, P., Li, Z., Xiao, F., Jiang, H., Wu, S., Tang, M., Yuan, F., Li, X., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52059-1 · Cited by 12
Stilgenbauer, L., Chen, Q., Pungi, D., James, N. M., Jayarathne, H. S. M., Koshko, L., Scofield, S., Zhang, K., & Sadagurski, M. (2025) · Molecular Metabolism · doi:10.1016/j.molmet.2025.102128 · Cited by 12
“NF-k B signaling and ER stress response play major roles in mediating pro-in fl ammation in these cell types under over-nutrition or with advanced aging [28 e 30].”
PINK1-dependent NFKB signaling contributes to amyloid pathology in Alzheimer disease
Du, F., Yu, Q., Hu, G., Lin, C., & Yan, S. S. (2025) · Autophagy · doi:10.1080/15548627.2025.2463322 · Cited by 13
“Emerging evidence demonstrates the role of NFKB in the processes of aging and neurodegenerative diseases [17,41,42].”
Putilina, M. V., & Grishin, D. V. (2021) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-021-01108-z · Cited by 12
Rzheshevsky, A. V. (2014) · Biochemistry (Moscow) · doi:10.1134/s0006297914100071 · Cited by 11
Sun, Z., Zhao, L., Su, L., Fang, Q., Xu, C., Su, Y., Liang, Y., Li, G., Xue, Y.-X., Tong, T., et al. (2019) · Aging · doi:10.18632/aging.101932 · Cited by 11
“NF-κB activity increases with aging in a variety of tissues of mammals [7-13] and contributes to a number of age-related disorders and pathologies [14-21].”
BackgroundInfluentialUnraveling the Paradoxical Action of Androgens on Muscle Stem Cells.
Seo, J., Kim, J.-H., & Kong, Y. (2019) · Europe PMC (PubMed Central) · doi:10.14348/molcells.2019.0004 · Cited by 12
“Recent studies have suggested the possibilities that aging with low androgen levels may result in systemic aging (Zhang et al., 2013) and dysfunctional muscle stem cells (Carlson and Conboy, 2007; Conboy et al., 2005).”
Backgroundvan Gastel, J., Cai, H., Cong, W., Chadwick, W., Daimon, C. M., Leysen, H., Hendrickx, J. O., Schepper, R. D., Vangenechten, L., Turnhout, J. V., et al. (2019) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2019.111150 · Cited by 11
Wang, Z., Khor, S., & Cai, D. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.12.001 · Cited by 11
“Rotarod test was performed as similarly described in our prior studies [34,35].”
MethodSelf-citationTang, Y., Zuniga-Hertz, J. P., Han, C., Yu, B., & Cai, D. (2020) · eLife · doi:10.7554/elife.52580 · Cited by 11
“All behavior tests were performed in the behavioral testing room as previously described (Zhang et al., 2013).”
MethodSelf-citationBrain is an endocrine organ through secretion and nuclear transfer of parathymosin
Yu, B., Tang, Y., & Cai, D. (2020) · Life Science Alliance · doi:10.26508/lsa.202000917 · Cited by 11
“…cognitive disorders, and we recently appreciated that the hypothalamus is important for the endocrine control of whole-body aging (Satoh et al, 2013; Zhang et al, 2013), although the underlying cell mechanism involves hypothalamic neural stem/progenitor cells (htNSC) (Zhang et al, 2017).”
BackgroundMethodInfluentialSelf-citationMate, N. A., Shaji, R., Das, M., Jain, S., & Banerjee, A. (2022) · Amino Acids · doi:10.1007/s00726-022-03139-3 · Cited by 11
“Further we have corroboration from a GnRH-I therapy study and inhibition of inflammation showing promising results of reverting aging-associated disorders as well as improving lifespan (Zhang et al. 2013).”
BackgroundGeorge, A. J., Dong, B., Lail, H. L., Gomez, M. G., Hoffiz, Y. C., Ware, C. B., Fang, N., Murphy, A. Z., Hrabovszky, E., Wanders, D., et al. (2022) · iScience · doi:10.1016/j.isci.2022.104386 · Cited by 13
“Interestingly, both NF-kB and inhibitor of nuclear factor kappa B kinase subunit beta (IKK-b) activation reduce GnRH release from GT1-7 cells (Zhang et al., 2013).”
InfluentialInflammation, Stem Cells, and the Aging Hypothalamus
Mendelsohn, A. R., & Larrick, J. W. (2017) · Rejuvenation Research · doi:10.1089/rej.2017.2002 · Cited by 11
“Because of its important role in homeostasis, the hypothalamus has long been hypothesized as a potential master “regulator” of aging (neuroendocrine theories of aging), and recent evidence suggests that indeed aging-associated molecular and cellular changes in the hypothalamus impact systemic homeostasis and lifespan…”
InfluentialDownregulation of the NF-κB protein p65 is a shared phenotype among most anti-aging interventions
Elmansi, A. M., Kassem, A., Castilla, R. M., & Miller, R. A. (2024) · GeroScience · doi:10.1007/s11357-024-01466-9 · Cited by 11
“** p 0.01 ◂ phosphorylate the IκB-α inhibitor, which frees the dimer to translocate to the nucleus [15, 53].”
InfluentialKacimi, L., & Prévot, V. (2025) · Endocrinology · doi:10.1210/endocr/bqaf033 · Cited by 10
Gene therapy strategies for aging intervention
Jing, Y., Ren, J., Qu, J. T., & Liu, G. (2025) · Cell Insight · doi:10.1016/j.cellin.2025.100254 · Cited by 10
Self-citationNAD+ oscillation and hypothalamic neuronal functions
Tokizane, K., & Imai, S. (2021) · Faculty Reviews · doi:10.12703/r/10-42 · Cited by 10
Changes of discharge properties of neurons from dorsomedial hypothalamic nuclei during aging in rats
Moiseev, K. Y., Spirichev, A. A., Vishnyakova, P. A., Pankrasheva, L. G., & Masliukov, P. M. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.136168 · Cited by 11
Integrity of hypothalamic–pituitary‐testicular axis in exceptional longevity
Aleksić, S., Desai, D., Ye, K. Q., Duran, S., Gao, T., Crandall, J. P., Atzmon, G., Barzilai, N., & Milman, S. (2022) · Aging Cell · doi:10.1111/acel.13656 · Cited by 9
“…is recognized as an important contributor to systemic aging (Chellappa et al., 2019; Debarba et al., 2022; Sadagurski et al., 2017; Sadagurski, Landeryou, Cady, Bartke, et al., 2015; Sadagurski, Landeryou, Cady, Kopchick, et al., 2015; Wang et al., 2021; Zhang et al., 2013; Zhang et al., 2017).”
BackgroundSleep–wake patterns are altered with age, Prdm13 signaling in the DMH, and diet restriction in mice
Tsuji, S., Brace, C. S., Yao, R., Tanie, Y., Tada, H., Rensing, N. R., Mizuno, S., Almunia, J. A., Kong, Y., Nakamura, K., et al. (2023) · Life Science Alliance · doi:10.26508/lsa.202301992 · Cited by 10
“Although DMH neurons are linked to sleep (Zhong et al, 2022), aging and longevity control (Satoh et al, 2013; Zhang et al, 2013; Zhang et al, 2017), and also activated by psychological stress (Kataoka et al, 2014), the involvement of DMH neurons in sleep control has not been fully elucidated.”
BackgroundMechanisms of Action of Curcumin on Aging
Carvalho, A. C., Gomes, A. C., Pereira‐Wilson, C., & Lima, C. F. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801816-3.00035-2 · Cited by 10
Opportunities and Challenges in Stem Cell Aging
Larijani, B. A., Heravani, N. F., Alaei, S., Rezaei–Tavirani, M., Alavi-Moghadam, S., Payab, M., Goodarzi, P., Tayanloo-Beik, A., Aghayan, H. R., & Arjmand, B. (2021) · Advances in experimental medicine and biology · doi:10.1007/5584_2021_624 · Cited by 10
Basha, E., Eltokhy, A. K., Eltantawy, A. F., Heabah, N. A. E.-G., Elshwaikh, S. L., & El-Harty, Y. M. (2022) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-022-02739-y · Cited by 10
Jylhävä, J., Kananen, L., Raitanen, J. A., Marttila, S., Nevalainen, T., Hervonen, A., Jylhä, M. K., & Hurme, M. (2016) · Oncotarget · doi:10.18632/oncotarget.8278 · Cited by 10
Stem Cell Models: A Guide to Understand and Mitigate Aging?
Brunauer, R., Alavez, S., & Kennedy, B. K. (2016) · Gerontology · doi:10.1159/000449501 · Cited by 10
Cau, P., Navarro, C. L., Harhouri, K., Roll, P., Sigaudy, S., Kaspi, É., Perrin, S., Sandre‐Giovannoli, A. D., & Lévy, N. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.03.022 · Cited by 10
Reappraisal of the Concept of Accelerated Aging in Neurodegeneration and Beyond
Statsenko, Y. A., Kuznetsov, N. V., Morozova, D., Liaonchyk, K., Simiyu, G. L., Smetanina, D., Kashapov, A., Meribout, S., Gorkom, K., Hamoudi, R., et al. (2023) · Cells · doi:10.3390/cells12202451 · Cited by 8
A narrative review on inflammaging and late-onset hypogonadism
Xing, D., Jin, Y., & Jin, B. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1291389 · Cited by 12
Distribution of lipid droplets in hippocampal neurons and microglia: impact of diabetes and exercise
Seferi, G., Mjønes, H. S., Havik, M., Reiersen, H., Dalen, K. T., Nordengen, K., & Morland, C. (2024) · Life Science Alliance · doi:10.26508/lsa.202302239 · Cited by 9
“Their ability to consume lipid-rich materials correlated to the degree of neuroin fl ammation, as proin fl ammatory signals were reported to enhance the internalization of lipids (47, 48).”
BackgroundNF-κB-mediated developmental delay extends lifespan in Drosophila
Kang, P., Liu, P., Hu, Y., Kim, J., Kumar, A., Dorneich-Hayes, M. K., Murzyn, W. A., Anderson, Z. J., Frank, L. N., Kavlock, N., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2420811122 · Cited by 8
SIRT2 and NAD + Boosting Broadly Suppress Aging‐Associated Inflammation
Barthez, M., Song, Z., Feng, Y., Wang, Y., Wang, C.-L., & Chen, D. (2025) · Aging Cell · doi:10.1111/acel.70162 · Cited by 11
Zhu, Y., Fang, X., Zhang, S., Liao, Y., Lin, H., Chen, P., Yang, M., Huang, J. J., & Wang, X. (2026) · International Journal of Nanomedicine · doi:10.2147/ijn.s589123 · Cited by 14
“103 Consequently, heightened inflammatory responses, diminished immune surveillance of pathogens and precancerous cells, alterations in the composition of the pericellular and extracellular milieu, and dysregulation of neurohormonal signaling (eg, renin-angiotensin, adrenergic, and insulin-IGF1…”
IKKβ signaling mediates metabolic changes in the hypothalamus of a Huntington disease mouse model
Soylu-Kucharz, R., Khoshnan, A., & Petersén, Å. (2022) · iScience · doi:10.1016/j.isci.2022.103771 · Cited by 9
Beyond the Lab: What We Can Learn about Cancer from Wild and Domestic Animals
Schraverus, H., Larondelle, Y., & Page, M. M. (2022) · Cancers · doi:10.3390/cancers14246177 · Cited by 10
“Differences have been reported in DNA repair capacity via a positive selection for DNA repair enzymes, such as Ku80 that is involved in the repair of DNA double strand breaks [64].”
BackgroundRole of Estrogen Receptor α in Aging and Chronic Disease
Isola, J. V. V., Ko, S.-H., Ocañas, S. R., & Stout, M. B. (2023) · Advances in Geriatric Medicine and Research · doi:10.20900/agmr20230005 · Cited by 13
“With advancing age, gonadal and neuroendocrine changes occur that result in declines in sex hormone production [18], and thus, declines in negative feedback within the HPG axis [19,20].”
BackgroundSerum Stem Cell Factor Level Predicts Decline in Kidney Function in Healthy Aging Adults
Zhang, W., Jia, L., Liu, D., Chen, L., Wang, Q., Song, K., Nie, S., Ma, J., Chen, X., Xiu, M., et al. (2019) · The journal of nutrition health & aging · doi:10.1007/s12603-019-1253-3 · Cited by 9
Cárdenas‐Tueme, M., Montalvo-Martínez, L., Maldonado‐Ruiz, R., Camacho‐Morales, A., & Reséndez‐Pérez, D. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00013 · Cited by 10
Dolcetti, F. J. C., Lockhart, E. F., Acuña, F., Herrera, M. L., Cervellini, S., Barbeito, C. G., Grassi, D., Arévalo, M., & Bellini, M. J. (2022) · Aging · doi:10.18632/aging.204360 · Cited by 11
“We suggest that IGF1 gene therapy may have a protective effect against reproductive decline. endocrinological as well as inflammatory events [1–3].”
InfluentialYang, Y., Liu, Y.-P., Bao, W., Chen, J.-S., & Xi, X. (2020) · Translational Cancer Research · doi:10.21037/tcr.2020.03.71 · Cited by 9
“The products were then purified and enriched with PCR, in order to construct the final cDNA library.”
InfluentialChen, W., Chen, X., Yao, L., Feng, J., Li, F., Shan, Y., Ren, L., Zhuo, C., Feng, M., Zhong, S., et al. (2024) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2024.06.020 · Cited by 7
“By blocking the activation of I κ B kinase beta (IKK-β ) and nuclear factor kappa B (NF-κ B) in the aging hypothalamus or brain, aging can be delayed and lifespan extended [5].”
Usmani, S. S., Jung, H., Zhang, Q., Kim, M. W., Choi, Y., Çağlayan, A. B., & Cai, D. (2024) · Nature Communications · doi:10.1038/s41467-024-53507-8 · Cited by 10
Self-citationAguilar, G. R., Vidal, B., Ji, H., Evenblij, J., Ji, H., Valperga, G., Liao, C., Fang-Yen, C. M., & Hobert, O. (2025) · PLoS Biology · doi:10.1371/journal.pbio.3002979 · Cited by 8
Zagmutt, S., Rodriguez-Garcia, M., Bolaños-Hurtado, M., Reguera, A. C., Casals, N., & Rodríguez‐Rodríguez, R. (2025) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-025-09992-3 · Cited by 12
“Pioneering studies from Dongsheng Cai’s lab published in 2017, uncovered that hypothalamic inflammation can programmatically regulate whole-body aging [106, 107].”
The brain-joint axis: links between osteoarthritis and neurodegenerative disorders in aging
Rabie, M. A., Madry, H., Cucchiarini, M., & Sayed, N. S. E. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.10.023 · Cited by 13
Current understanding of essential trace elements in intrahepatic cholestasis of pregnancy
Shan, D., Chen, Q., Xie, Y., Dai, S., & Hu, Y. (2024) · BioMetals · doi:10.1007/s10534-024-00586-1 · Cited by 8
“Inflammatory cells are then activated, and the inflammatory responses are then augmented after activation of NF-κB, p53/p21 and other signaling pathways (Zhang et al. 2013).”
Tian, X., Zhao, Z., Zhao, J., Su, D., He, B., Shi, C., & Shi, Y. (2024) · Behavioural Brain Research · doi:10.1016/j.bbr.2024.114943 · Cited by 8
A Brain Anti-Senescence Transcriptional Program Triggered by Hypothalamic-Derived Exosomal microRNAs
Krarup, J., Araya, L., Álvarez, F., Bórquez, D. A., & Urrutia, P. J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25105467 · Cited by 11
Olberg, D. E., Andressen, K. W., Levy, F. O., Klaveness, J., Haraldsen, I., & Sutcliffe-Goulden, J. (2014) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2014.02.002 · Cited by 8
Oszkiel, H., Wilczak, J., & Jank, M. (2014) · Genes & Nutrition · doi:10.1007/s12263-014-0427-1 · Cited by 8
“In addition, Zhang et al. (2013) pointed out the relationship between the pituitary GnRH and immunoaging.”
Dual roles for bone marrow‐derived Sca‐1 cells in cardiac function
Tobin, S. W., Li, S., Li, J., Wu, J., Yeganeh, A., Pan, Y., Weisel, R. D., & Li, R. (2017) · The FASEB Journal · doi:10.1096/fj.201601363rr · Cited by 8
Self-citationThe Endocrinology of Aging: A Key to Longevity “Great Expectations”
Reddy, S. S. K., & Chaiban, J. T. (2017) · Endocrine Practice · doi:10.4158/ep171793.ra · Cited by 9
Yakabi, K., Yamaguchi, N., Ono, S., Yoshida, N., Hosomi, E., Hayashi, K., Ochiai, M., Maezawa, K., & Nomura, K. (2017) · Current Therapeutic Research · doi:10.1016/j.curtheres.2017.07.003 · Cited by 8
“In addition, the influence of ghrelin on microglial behavior in the brain may influence the prognosis of some neurologic disorders, such as multiple sclerosis, supporting the abovementioned possible mechanism.(43,44) The 4-week RKT treatment did not lead to deterioration in the motor function of our patients.”
BackgroundBekker, R. B. W., Fjellaksel, R., Hjørnevik, T., Nuruddin, S., Rafique, W., Hansen, J. H., Sundset, R., Haraldsen, I., & Riss, P. J. (2020) · ChemMedChem · doi:10.1002/cmdc.202000256 · Cited by 8
Shi, C., Li, G., Guo, H., & Liu, X. (2020) · Neuroreport · doi:10.1097/wnr.0000000000001548 · Cited by 8
Multi-Level Regulatory Interactions between NF-κB and the Pluripotency Factor Lin28
Mills, W. T., Nassar, N. N., Ravindra, D., Li, X., & Meffert, M. K. (2020) · Cells · doi:10.3390/cells9122710 · Cited by 8
“One potential explanation could lie in different cell-intrinsic versus systemic outcomes of NF-κB activation; a systemic impact of NF-κB activation on inhibiting gonadotrophin-releasing hormone (GnRH) release is postulated to mediate the subsequent impairment in neurogenesis [74].”
BackgroundTherapeutic effects and perspective of stem cell extracellular vesicles in aging and cancer
Liu, Y., Cheng, Y., Wang, S., Su, Y., Liu, Y., Li, C., Jin, L., Wan, Q., Sang, X., & Wang, Z. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.30212 · Cited by 9
“Neural stem cell and its EVs are found to be able to slowdown aging with the fact that they can improve the endurance, mobility, coordination, sociability, and new things cognization in aged mice (Zhang et al., 2013; Zhang et al., 2017).”
BackgroundCan inflammation regulate systemic aging?
Patel, P., Lockey, R. F., & Kolliputi, N. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.04.011 · Cited by 8
“Conversely, upon the blocking of this hypothalamic NF-κB and IKK-β pathway in mouse models, the mice exhibited a decelerated aging process and an increasedmedian longevity by nearly 20%, as compared to controls (Zhang et al., 2013).”
BackgroundInfluentialInvolvement of inhibitory PAS domain protein in neuronal cell death in Parkinson’s disease
Torii, S., Kasai, S., Suzuki, A., Todoroki, Y., Yokozawa, K., Yasumoto, K.-I., Seike, N., Kiyonari, H., Mukumoto, Y., Kakita, A., et al. (2015) · Cell Death Discovery · doi:10.1038/cddiscovery.2015.15 · Cited by 8
Longevity control by the nervous system: Sensory perception, stress response and beyond
Lin, C.-T., He, C.-W., Huang, T., & Pan, C. (2017) · Translational Medicine of Aging · doi:10.1016/j.tma.2017.07.001 · Cited by 9
Levi, N. J., Wilson, C. W., Redweik, G. A. J., Gray, N. W., Grzybowski, C. W., Lenkey, J. A., Moseman, A. W., Bertsch, A. D., Dao, N., & Walsh, H. E. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2018.07.011 · Cited by 8
HPG-Dependent Peri-Pubertal Regulation of Adult Neurogenesis in Mice
Trova, S., Bovetti, S., Pellegrino, G., Bonzano, S., Giacobini, P., & Peretto, P. M. (2020) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2020.584493 · Cited by 8
“…that GnRH per semay play extra-reproductive functions in the brain (Merchenthaler et al., 1989; Shinoda et al., 1989; Lin et al., 2004; Balasubramanian et al., 2010), and, accordingly, a link between GnRH secretion and DG neurogenesis has been previously suggested in aged mice (Zhang et al., 2013).”
BackgroundShi, C., Shi, R., & Guo, H. (2020) · Neuroreport · doi:10.1097/wnr.0000000000001424 · Cited by 8
Metadata
- Authors
- Zhang, G., Li, J., Purkayastha, S., Tang, Y., Zhang, H., Yin, Y., Li, B., Liu, G., & Cai, D.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Cai, Dongsheng
- Venue
- Nature
- Published
- 2013-05
- Volume
- 497
- Issue
- 7448
- Pages
- 211-216
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3756938
- OpenAlex
- W2098009444
- Cited by
- 834
- References
- 45
- Citations by year
- 2026: 36 · 2025: 45 · 2024: 57 · 2023: 54 · 2022: 58 · 2021: 76 · 2020: 76 · 2019: 62 · 2018: 64 · 2017: 78 · 2016: 72 · 2015: 62 · 2014: 59 · 2013: 34
- FWCI
- 26.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute on Aging (R01AG031774)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK078750)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- lifespan extension, IKKβ, NF-κB, gonadotropin-releasing hormone, neurogenesis, metabolic inflammation, reproductive aging, GnRH treatment
- MeSH terms
- Aging, Animals, Brain, Cognition, Female, Hypothalamus, Gonadotropin-Releasing Hormone, Longevity, Male, Mice, Inbred C57BL, Reproduction, NF-kappa B, Microglia, Mice, Knockout, Mice, I-kappa B Kinase, Neurogenesis
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
