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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.
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“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
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“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
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“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
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“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]
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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
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Self-citationZhao, H., Liao, M., Huo, R., He, T., Tian, H., Li, Z., Chen, C., Yu, Z., Chai, J., Song, X., et al. (2026) · Cell · doi:10.1016/j.cell.2026.01.016 · Cited by 8
Li, J., Gui, C., Yao, H., Luo, C., Song, H., Lin, H., Xu, Q., Chen, X., Huang, Y., Luo, J., et al. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.871088 · Cited by 7
“A previous study revealed that IKK-β and NF-κB mediate agingrelated hypothalamic GNRH decline, and GNRH treatment amends aging-impaired neurogenesis and decelerates aging (Zhang et al., 2013).”
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Abdrabou, A. M. (2023) · Kinases and Phosphatases · doi:10.3390/kinasesphosphatases2010002 · Cited by 7
“Notably, the activation of IKK β is frequently prompted by proinflammatory stimuli, connecting it to persistent inflammation [89].”
BackgroundHuang, J., Wang, W., Lin, W., CAI, H., ZHU, Z., Waqas, A., Zhang, Q. Y., LIU, J., Zhang, Y., Li, R., et al. (2024) · Biocell · doi:10.32604/biocell.2024.053148 · Cited by 7
“Some studies believe that the hypothalamus plays a signi fi cant role in the occurrence of senescence [53,54], but the mechanism is still unclear.”
BackgroundXu, W., An, X., Zhang, N., Li, L., Zhang, X., Wang, Y., Wang, L., & Sun, Y. (2019) · BioScience Trends · doi:10.5582/bst.2019.01162 · Cited by 7
Martín‐Segura, A., Casadomé‐Perales, Á., Fazzari, P., Mas, J. M., Artigas, L., Valls, R., Nebreda, Á. R., & Dotti, C. G. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00675 · Cited by 7
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Nambu, Y., Ohira, K., Morita, M., Yasumoto, H., Kurganov, E., & Miyata, S. (2021) · Neuroscience Research · doi:10.1016/j.neures.2021.05.012 · Cited by 7
Queen, N. J., Hong, D., Huang, W., Mo, X. M., Wilkins, R. K., Zhu, T., Wu, X., & Cao, L. (2021) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-21-0085 · Cited by 7
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Huang, L., Xu, L., Yun, C., Qiao, J., & Qi, X. (2025) · Life Medicine · doi:10.1093/lifemedi/lnaf029 · Cited by 8
“This inflammatory cascade transcriptionally represses GnRH via direct promoter binding—reducing transcriptional activity by 50%—while impairing kisspeptin neuron function [21, 22].”
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Suk, K. (2026) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2026.102915 · Cited by 6
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
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Poser, M., Sing, K. E. A., Ebert, T., Ziebolz, D., & Schmalz, G. (2023) · Biogerontology · doi:10.1007/s10522-023-10047-w · Cited by 7
“Alterations appear on the neuronal, neuroendocrine and endocrine level (Rera et al. 2011; Zhang et al. 2013; Russell and Kahn 2007; Rando and Chang 2012).”
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“The important role of NFκB in ageing is confirmed by pharmacological and genetic evidence showing that inhibition of the NFκB complex can increase longevity of mice by about 20% (Moskalev and Shaposhnikov 2011; Zhang et al. 2013).”
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Shrestha, S., Shrestha, A., Park, J., Lee, D., Cho, J. S., Shrestha, B., & Baek, N. (2014) · Nepal Journal of Science and Technology · doi:10.3126/njst.v14i2.10415 · Cited by 6
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Wu, C. J., Bendriem, R. M., Freed, W. J., & Lee, C. (2021) · Restorative Neurology and Neuroscience · doi:10.3233/rnn-211161 · Cited by 7
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Queen, N. J., Huang, W., Zou, X., Mo, X. M., & Cao, L. (2023) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2023.09.004 · Cited by 7
Neufeld, K. M., Mao, Y., West, C. L., Ahn, M., Hameed, H. A. A., Iwashita, E., Stanisz, A. M., Forsythe, P., Barbut, D., ZASLOFF, M. A., et al. (2024) · Communications Biology · doi:10.1038/s42003-023-05623-2 · Cited by 6
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Mustafin, R. N., & Хуснутдинова, Э. К. (2018) · Advances in Gerontology · doi:10.1134/s2079057018030128 · Cited by 6
Ou, Y., Zhou, M., Wu, G., Gong, H., Li, K., Wang, X., Peng, J., Niu, P., Liu, Y., Qi, S., et al. (2020) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2020.108694 · Cited by 6
“However, most researchers([2-7]) choose to present histopathological results by analysis of separate hypothalamic or pituitary coronal sections.”
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Haefke, A. S., & Ewald, C. Y. (2020) · BIO-PROTOCOL · doi:10.21769/bioprotoc.3833 · Cited by 6
“TTBT assays have also been used to demonstrate the effect of lifespan-altering interventions involving hypothalamic programming, in which shorter-lived MBH-IKK-β mice exhibited greater TTBTs than both the control group and the longer-lived MBH-IκB-α mice (Zhang et al., 2013).”
MethodLi, R., Li, Y., Tian, M., Zhang, H., Lou, L., Liu, K., Zhang, J., Zhao, Y., Zhang, J., Le, S., et al. (2021) · FEBS Letters · doi:10.1002/1873-3468.14242 · Cited by 7
Self-citationXu, H., Sun, B., Liao, Z., Pribytkova, E., Zhang, Q., Wei, Y., & Liang, M. (2019) · Aquaculture Research · doi:10.1111/are.14307 · Cited by 6
Anisimov, V. N. (2014) · Interdisciplinary topics in gerontology and geriatrics · doi:10.1159/000364982 · Cited by 6
Functional and multi-omic aging rejuvenation with GLP-1R agonismPreprint
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Self-citationMa, T., Tan, L., Shen, C., Jin, X., Li, H., & Liang, J. (2025) · Environmental Science & Technology · doi:10.1021/acs.est.5c01532 · Cited by 5
Palmisano, M., Ramunno, C. F., Farhat, E., Dvir‐Ginzberg, M., Lutz, B., de Almodóvar, C. R., & Bilkei‐Gorzó, A. (2024) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2024.111954 · Cited by 5
“…two possible mechanisms by which hypothalamic neuroinflammation – in this case, due to the lack of CB1 receptor signaling – may influence the course of ageing: the possible role of reduced GnRH production (Zhang et al., 2013a) and, alternatively, a disturbed IGF-1 signaling (Gubbi et al., 2018a).”
BackgroundInfluentialSharif, A., & Prévot, V. (2024) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2024.101154 · Cited by 7
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Kurtak, K. A. (2013) · Rejuvenation Research · doi:10.1089/rej.2013.1485 · Cited by 5
Chatterjee, O., Gopalakrishnan, L., Mol, P., Advani, J., Nair, B. G., Shankar, S. K., Mahadevan, A., & Prasad, T. S. K. (2021) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2021.0158 · Cited by 5
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Santos, C. L., Weber, F. B., Belló‐Klein, A., Bobermin, L. D., & Quincozes‐Santos, A. (2024) · Neurochemical Research · doi:10.1007/s11064-024-04196-8 · Cited by 5
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Wimer, L. A., Kaneshiro, K. R., Ramirez, J., Bose, N., Valdearcos, M., Shanmugam, M. M., Farrera, D. O., Singh, P. P., Beck, J., Sellegounder, D., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116422 · Cited by 5
“…assessed the effect of individual compounds on food consumption rates, body weights, and abbreviated hormonal analysis, future studies testing individual components in varied combinations will be essential to determine whether certain combinations produce synergistic effects for specific outcomes.”
Perspective on Stem Cells in Developmental Biology, with Special Reference to Neuroendocrine Systems
Rizzoti, K., Pires, C., & Lovell-Badge, R. H. (2016) · Research and perspectives in endocrine interactions · doi:10.1007/978-3-319-41603-8_11 · Cited by 5
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BackgroundInfluentialGenetics of aging and longevity
Moskalev, A., Proshkina, E., Belyi, A. A., & Solovev, I. A. (2016) · Vavilov Journal of Genetics and Breeding · doi:10.18699/vj16.171 · Cited by 6
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Nunn, A. V. W., Guy, G. W., & Bell, J. D. (2017) · International Journal of Neurorehabilitation · doi:10.4172/2376-0281.1000272 · Cited by 5
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Menéndez, J. A., Cuyàs, E., Folguera-Blasco, N., Verdura, S., Martín-Castillo, B., Joven, J., & Alarcón, T. (2019) · Aging · doi:10.18632/aging.102180 · Cited by 5
“, aspirin, non-steroidal anti-inflammatory drugs [NSAIDs] or nordihydroguaiaretic acid) [4449], which may even operate at the hypothalamus level to impede systemic inflammation-driven aging [50].”
BackgroundShi, C., Shi, R., Guo, H., Shi, Y., & Liu, X. (2020) · Neuroreport · doi:10.1097/wnr.0000000000001488 · Cited by 5
The science of mind body medicine and the public health challenges of today
Fricchione, G. L. (2014) · South African Journal of Psychology · doi:10.1177/0081246314541025 · Cited by 7
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BackgroundExtension of Life Span in Laboratory Mice
Unnikrishnan, A., Deepa, S. S., Herd, H. R., & Richardson, A. G. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811353-0.00019-1 · Cited by 7
Update on Hypothalamic Inflammation and Gliosis: Expanding Evidence of Relevance Beyond Obesity
Huang, A., Yeum, D., SEWAYBRICKER, L. E., Aleksić, S., Thomas, M., Melhorn, S. J., Feng, Y., & Schur, E. A. (2025) · Current Obesity Reports · doi:10.1007/s13679-024-00595-8 · Cited by 7
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Li, Q., An, H., Bai, R., Sun, Q., Yang, R., Xin, T., Zhuang, Z., Lu, Y., Tang, Y., Chen, G., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115910 · Cited by 5
Self-citationInflammation and vasopressin hypersecretion in aging
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Баранов, В. С., Glotov, O. S., & Baranova, E. V. (2014) · Advances in Gerontology · doi:10.1134/s2079057014040055 · Cited by 4
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Seong, K.-J., Mun, B.-R., Kim, S., Choi, W., Lee, S. J., Jung, J., & Kim, W.-J. (2025) · Life Sciences · doi:10.1016/j.lfs.2025.123490 · Cited by 4
García‐Contreras, R., Scougall‐Vilchis, R. J., Contreras‐Bulnes, R., Sugimoto, M., Nakajima, H., & Sakagami, H. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-42867-5.00003-5 · Cited by 4
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Çakır, I., & Nillni, E. A. (2018) · Springer eBooks · doi:10.1007/978-3-319-89506-2_4 · Cited by 4
Fan, Y., Li, C., Pei, W., Tan, T., Li, R., Qiao, J., & Yu, Y. (2020) · Aging · doi:10.18632/aging.103682 · Cited by 4
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BackgroundKim, D., Lee, Y., Kim, H., Park, Y. J., Hwang, H., Rhim, H., Kang, T., Choi, C. W., Lee, B., & Kim, M. S. (2021) · Scientific Reports · doi:10.1038/s41598-021-00074-3 · Cited by 4
Zhang, P., Zhang, J., Wei, J., Feng, S., Qi, Y., Yang, C.-H., & Jiang, Y. (2022) · Annals of Translational Medicine · doi:10.21037/atm-21-6390 · Cited by 3
“Three major MAPK families, including the extracellular response kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, are widely involved in mammalian systems (21).”
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Liu, Y., Guo, Y., Peng, H., Zhou, H., Su, T., Yang, M., Guo, Q., Ye, X., Huang, Y., & Jiang, T. (2022) · Cell Proliferation · doi:10.1111/cpr.13332 · Cited by 4
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Shimokawa, I. (2023) · Pathology International · doi:10.1111/pin.13387 · Cited by 3
Lysine-36 of Drosophila histone H3.3 supports adult longevity
Brown, J. C., McMichael, B. D., Vandadi, V., Mukherjee, A., Salzler, H. R., & Matera, A. G. (2024) · G3 Genes Genomes Genetics · doi:10.1093/g3journal/jkae030 · Cited by 4
Prahlad, V., & Chikka, M. R. (2018) · Wiley eBooks · doi:10.1002/9781118772034.ch3 · Cited by 4
Activin Signaling Regulates Autophagy and Cardiac Aging through mTORC2Preprint
Chang, K., Kang, P., Liu, Y., Huang, K., Taylor, E., Sagona, A. P., Nezis, I. P., Bodmer, R., Ocorr, K. A., & Bai, H. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/139360 · Cited by 4
Kang, P., Liu, P., Kim, J., Kumar, A., Bolton, M., Murzyn, W. A., Anderson, Z. J., Frank, L. N., Kavlock, N., Hoffman, E., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.30.560323 · Cited by 4
Choi, Y., Kim, M. W., Go, G., & Cai, D. (2026) · Nature Metabolism · doi:10.1038/s42255-026-01474-3 · Cited by 4
Self-citationBiological Clocks: Why We Need Them, Why We Cannot Trust Them, How They Might Be Improved
Mitteldorf, J. (2024) · Biochemistry (Moscow) · doi:10.1134/s0006297924020135 · Cited by 3
“Age-dependent increase in the pro-inflammatory signal NF-κB seems to emanate directly from the hypothalamus [68].”
An Update on Neuroaging on Earth and in Spaceflight
Kuznetsov, N. V., Statsenko, Y. A., & Ljubisavljević, M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26041738 · Cited by 6
Antiaging therapy: a prospective hypothesis
Bonjar, L. S., & Bonjar, M. R. S. (2015) · Drug Design Development and Therapy · doi:10.2147/dddt.s71216 · Cited by 3
“In 2013, Zhang et al at the Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, demonstrated that the hypothalamus was critical for the progress of whole-body aging in mice, and the elemental basis involved hypothalamic immunity mediated by IκB kinase-β (IKK-β), nuclear factor κ…”
Rožman, P. J., Jazbec, K., & Jež, M. (2018) · InTech eBooks · doi:10.5772/intechopen.71764 · Cited by 4
Dalvi, P. S., Loganathan, N., McIlwraith, E. K., Tran, A., & Belsham, D. D. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819801-8.00002-8 · Cited by 3
Human Alpha 1 Antitrypsin Suppresses NF-κB Activity and Extends Lifespan in Adult Drosophila
Yuan, Y., Belkum, M. V., O’Brien, A., Garcia, A., Troncoso, K., Elshikha, A. S., Zhou, L. J., & Song, S. (2022) · Biomolecules · doi:10.3390/biom12101347 · Cited by 5
“The suppression of NF-κB in the brain by transgenic inhibition of IKK-β significantly extended the lifespan of mice and improved aging-related cognition decline, muscle weakness, skin atrophy, bone loss, and collagen cross-linking [18].”
BackgroundBarbut, D., Kinney, W. A., Chen, H., Stewart, A. F. R., Hecksher‐Sørensen, J., Zhang, C., Fleming, A., Zemel, M. B., & ZASLOFF, M. A. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15940 · Cited by 3
Cell-Based Models to Study GnRH Neuron Physiology
Maggi, R. (2017) · MOJ Anatomy & Physiology · doi:10.15406/mojap.2017.03.00119 · Cited by 3
Epigenetic and transcriptional regulation of GnRH gene under altered metabolism and ageing
Chandra, K., Banerjee, A., & Das, M. (2021) · The Nucleus · doi:10.1007/s13237-021-00374-z · Cited by 3
Musi, N., & Bartke, A. (2015) · Springer eBooks · doi:10.1007/978-3-319-23246-1_12 · Cited by 5
Hypothalamic Microinflammation: New Paradigm In Obesity And Metabolic Disease
Meiliana, A., Dewi, N. M., & Wijaya, A. (2020) · The Indonesian Biomedical Journal · doi:10.18585/inabj.v12i3.1235 · Cited by 2
Hypothalamic gene transfer of BDNF promotes healthy aging
Cao, L., Ali, S., & Queen, N. J. (2021) · Vitamins and hormones · doi:10.1016/bs.vh.2020.12.003 · Cited by 4
Sirtuins, healthspan, and longevity in mammals
Kumar, S., Giblin, W., & Lombard, D. B. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-815962-0.00005-6 · Cited by 2
Single cell analysis of the aging female hypothalamusPreprint
Hajdarovic, K. H., Yu, D., Hassell, L.-A., Evans, S. A., Packer, S., Neretti, N., & Webb, A. E. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.07.434282 · Cited by 3
“The number of differentially 274 expressed genes appears to be a function of the number of nuclei per cluster, for example, the 275 Npas3/Gpc cluster (12) which has a large number of nuclei (1923) shows 224 genes 276 downregulated in age and 70 genes upregulated in age.”
BackgroundThree Tiers to biological escape velocity: The quest to outwit aging
Palmer, R. D. (2022) · AGING MEDICINE · doi:10.1002/agm2.12231 · Cited by 2
Diet-Induced Overweight Conditions: Effect on Brain Structure, Cognitive Function, and Neurogenesis
Khatun, A., Patra, S., Ghosh, K., Pradhan, S., & Chakrabarti, S. (2023) · IntechOpen eBooks · doi:10.5772/intechopen.110610 · Cited by 2
Li, L., Wu, G., Xu, X., Yang, J., Yi, L., Yang, Z., Mo, Z., Li, X., Shan, Y., Yu, Z., et al. (2024) · eLife · doi:10.7554/elife.100346.4 · Cited by 2
Gulej, R., Patai, R., Kiss, T., Chandragiri, S. S., Ekambaram, S., Nagaraja, R. Y., Nagy, D., Kordestan, K. V., Lakat, T., Tarantini, S., et al. (2025) · GeroScience · doi:10.1007/s11357-025-01953-7 · Cited by 4
Ottinger, M. A., Duffy, K., Schlappal, A., Sitzmann, B. D., Wu, J., & Zimmer, D. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.00156-2 · Cited by 2
Satoh, A. (2022) · Springer eBooks · doi:10.1007/978-981-16-7977-3_18 · Cited by 2
Expression of MicroRNA-200a/b/c in the Mediobasal Hypothalamic Nuclei with Aging
Порсева, В. В., Pankrasheva, L. G., Moiseev, K. Y., Anfimova, P. A., Emanuilov, A. I., Levshin, N. Y., Baranov, A. A., & Masliukov, P. M. (2023) · MicroRNA · doi:10.2174/2211536612666230810094531 · Cited by 2
Asmaz, E. D., Ceylani, T., Genç, A. İ., Sertkaya, Z. T., & Teker, H. T. (2025) · Biogerontology · doi:10.1007/s10522-025-10197-z · Cited by 2
“…et al. 2011), for cardiovascular ageing and improved endothelial function (Loffredo et al. 2013), age-related obesity, and metabolic syndromes (Zhang et al. 2013) and in improved antioxidant enzyme activities and reduced protein carboxylation in aged rats (Tripathi et al. 2021), indicating…”
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
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