Age-related hyperinsulinemia leads to insulin resistance in neurons and cell-cycle-induced senescence
Abstract
Prediabetes and Alzheimer's disease both increase in prevalence with age. The former is a risk factor for the latter, but a mechanistic linkage between them remains elusive. We show that prediabetic serum hyperinsulinemia is reflected in the cerebrospinal fluid and that this chronically elevated insulin renders neurons resistant to insulin. This leads to abnormal electrophysiological activity and other defects. In addition, neuronal insulin resistance reduces hexokinase 2, thus impairing glycolysis. This hampers the ubiquitination and degradation of p35, favoring its cleavage to p25, which hyperactivates CDK5 and interferes with the GSK3β-induced degradation of β-catenin. CDK5 contributes to neuronal cell death while β-catenin enters the neuronal nucleus and re-activates the cell cycle machinery. Unable to successfully divide, the neuron instead enters a senescent-like state. These findings offer a direct connection between peripheral hyperinsulinemia, as found in prediabetes, age-related neurodegeneration and cognitive decline. The implications for neurodegenerative conditions such as Alzheimer's disease are described.
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Obesity and hyperinsulinemia can trigger senescence and chronic inflammation, impairing brain homeostasis.
“Additionally, recent evidence suggests that obesity 119 and hyperinsulinemia 120 can also trigger senescence and chronic inflammation, impairing brain homeostasis.”
From Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies (2024) · cites this paper as [120]
DNA damage may play a central role in neuroinflammation associated with neurodegenerative disease.
“work establishing a role for senescence in the aging and diseased brain reveals DNA damage may play a central role in neuroinflammation associated with neurodegenerative disease.”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Chow et al, 2019
Senescent-like phenotypes in neurons have been noted in other models of aging and neurodegeneration.
“Senescent‐like phenotypes in neurons have also been noted in other models of aging and neurodegeneration (Chow et al, 2019; Moreno‐Blas et al, 2019).”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Chow et al, 2019
Cites
The limited in vitro lifetime of human diploid cell strains
Hayflick, L. (1965) · Experimental Cell Research · doi:10.1016/0014-4827(65)90211-9 · Cited by 5,876 · see citing works
Short-Term Synaptic Plasticity
Zucker, R. S., & Regehr, W. G. (2002) · Annual Review of Physiology · doi:10.1146/annurev.physiol.64.092501.114547 · Cited by 5,068 · see citing works
Hearing loss and cognitive decline in older adults
Lin, F. R., Yaffe, K., Xia, J., Xue, Q.-L., Harris, T. B., Purchase-Helzner, E., Satterfield, S., Ayonayon, H. N., Ferrucci, L., Simonsick, E. M., et al. (2013) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2013.1868 · Cited by 4,017 · see citing works
The ClusPro web server for protein–protein docking
Kozakov, D., Hall, D. R., Xia, B., Porter, K. A., Padhorny, D., Yueh, C., Beglov, D., & Vajda, S. (2017) · Nature Protocols · doi:10.1038/nprot.2016.169 · Cited by 3,297 · see citing works
Aging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954 · see citing works
Diabetes mellitus and the risk of dementia: The Rotterdam Study
Ott, A., Stolk, R. P., van Harskamp, F., Pols, H. A. P., Hofman, A., & Breteler, M. M. B. (1999) · Neurology · doi:10.1212/wnl.53.9.1937 · Cited by 2,175 · see citing works
HDOCK: a web server for protein–protein and protein–DNA/RNA docking based on a hybrid strategy
Yan, Y., Zhang, D., Zhou, P., Li, B., & Huang, S. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx407 · Cited by 1,479 · see citing works
Use of the Open Field Maze to Measure Locomotor and Anxiety-like Behavior in Mice
Seibenhener, M. L., & Wooten, M. C. (2015) · Journal of Visualized Experiments · doi:10.3791/52434 · Cited by 1,467 · see citing works
Senescence-associated β-galactosidase is lysosomal β-galactosidase.
Lee, B. Y., Han, J. A., Im, J. S., Morrone, A., Johung, K., Goodwin, E. C., Kleijer, W. J., DiMaio, D., & Hwang, E. S. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00199.x · Cited by 1,444 · see citing works
Nucleolar Arf sequesters Mdm2 and activates p53
Weber, J. D., Taylor, L. J., Roussel, M. F., Sherr, C. J., & Bar-Sagi, D. (1999) · Nature Cell Biology · doi:10.1038/8991 · Cited by 940 · see citing works
Insulin Resistance and Hyperinsulinemia
Shanik, M. H., Xu, Y., Škrha, J., Dankner, R., Zick, Y., & Roth, J. (2008) · Diabetes Care · doi:10.2337/dc08-s264 · Cited by 791 · see citing works
Hawley, S. A., Gadalla, A. E., Olsen, G. S., & Hardie, D. G. (2002) · Diabetes · doi:10.2337/diabetes.51.8.2420 · Cited by 696 · see citing works
Incretin-based therapies for type 2 diabetes mellitus
Lovshin, J. A., & Drucker, D. J. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.48 · Cited by 645 · see citing works
Can, A., Dao, D. T., Arad, M., Terrillion, C. E., Piantadosi, S. C., & Gould, T. D. (2011) · Journal of Visualized Experiments · doi:10.3791/3638 · Cited by 616 · see citing works
Tau protein aggregation is associated with cellular senescence in the brain
Musi, N., Valentine, J. M., Sickora, K. R., Baeuerle, E., Thompson, C. S., Shen, Q., & Orr, M. E. (2018) · Aging Cell · doi:10.1111/acel.12840 · Cited by 595 · see citing works
Synapsins as Regulators of Neurotransmitter Release
Hilfiker, S., Pieribone, V. A., Czernik, A. J., Kao, H.-T., Augustine, G. J., & Greengard, P. (1999) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.1999.0378 · Cited by 537 · see citing works
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
Kim, B., & Feldman, E. L. (2015) · Experimental & Molecular Medicine · doi:10.1038/emm.2015.3 · Cited by 357 · see citing works
PML regulates p53 stability by sequestering Mdm2 to the nucleolus
Bernardi, R., Scaglioni, P. P., Bergmann, S., Horn, H. F., Vousden, K. H., & Pandolfi, P. P. (2004) · Nature Cell Biology · doi:10.1038/ncb1147 · Cited by 348 · see citing works
van Houten, M., Posner, B. I., Kopriwa, B. M., & Brawer, J. R. (1979) · Endocrinology · doi:10.1210/endo-105-3-666 · Cited by 321 · see citing works
The Role of Insulin in Human Brain Glucose Metabolism
Bingham, E., Hopkins, D., Smith, D., Pernet, A., Hallett, W. A., Reed, L. J., Marsden, P. K., & Amiel, S. A. (2002) · Diabetes · doi:10.2337/diabetes.51.12.3384 · Cited by 293 · see citing works
Scherf, M., Klingenhoff, A., & Werner, T. A. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.3589 · Cited by 281 · see citing works
Fischer, A., Sananbenesi, F., Pang, P. T., Lu, B., & Tsai, L.-H. (2005) · Neuron · doi:10.1016/j.neuron.2005.10.033 · Cited by 277 · see citing works
A Technique for Serial Collection of Cerebrospinal Fluid from the Cisterna Magna in Mouse
Liu, L., & Duff, K. (2008) · Journal of Visualized Experiments · doi:10.3791/960 · Cited by 268 · see citing works
Glycogen Synthase Kinase 3β Phosphorylates Tau at Both Primed and Unprimed Sites
Cho, J.-H., & Johnson, G. V. W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m206236200 · Cited by 266 · see citing works
Kim, J., Grunke, S. D., Levites, Y., Golde, T. E., & Jankowsky, J. L. (2014) · Journal of Visualized Experiments · doi:10.3791/51863 · Cited by 250 · see citing works
Impaired insulin action in the human brain: causes and metabolic consequences
Heni, M., Kullmann, S., Preissl, H., Fritsche, A., & Häring, H.-U. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.173 · Cited by 245 · see citing works
Hamilton, A., & Hölscher, C. (2009) · NeuroReport · doi:10.1097/wnr.0b013e32832fbf14 · Cited by 227 · see citing works
Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia telangiectasia
Li, J., Chen, J., Ricupero, C. L., Hart, R. P., Schwartz, M. S., Kusnecov, A., & Herrup, K. (2012) · Nature Medicine · doi:10.1038/nm.2709 · Cited by 210 · see citing works
Self-citationCellular Senescence in Postmitotic Cells: Beyond Growth Arrest
Sapieha, P., & Mallette, F. A. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.03.003 · Cited by 193 · see citing works
Hyperinsulinemia and Cognitive Decline in a Middle-Aged Cohort
Young, S. E., Mainous, A. G., & Carnemolla, M. (2006) · Diabetes Care · doi:10.2337/dc06-0915 · Cited by 180 · see citing works
Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan
Templeman, N. M., Flibotte, S., Chik, J. H. L., Sinha, S., Lim, G. E., Foster, L. J., Nislow, C., & Johnson, J. D. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.06.048 · Cited by 148 · see citing works
Neuronal LRP1 Regulates Glucose Metabolism and Insulin Signaling in the Brain
Liu, C., Hu, J., Tsai, C., Yue, M., Melrose, H. L., Kanekiyo, T., & Bu, G. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.5180-14.2015 · Cited by 140 · see citing works
Glutamate mediates acute glucose transport inhibition in hippocampal neurons
Porras, O. H., Loaiza, A., & Barros, L. F. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1882-04.2004 · Cited by 139 · see citing works
Loss of Neuronal Cell Cycle Control in Ataxia-Telangiectasia: A Unified Disease Mechanism
Yang, Y. F., & Herrup, K. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4946-04.2005 · Cited by 130 · see citing works
Self-citationEffects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance
Hirvonen, J., Virtanen, K. A., Nummenmaa, L., Hannukainen, J. C., Honka, M., Bucci, M., Nesterov, S. V., Parkkola, R. K., Rinne, J. O., Iozzo, P., et al. (2011) · Diabetes · doi:10.2337/db10-0940 · Cited by 128 · see citing works
Salani, B., Marini, C., Río, A. D., Ravera, S., Massollo, M., Orengo, A. M., Amaro, A. A., Passalacqua, M., Maffioli, S., Pfeffer, U., et al. (2013) · Scientific Reports · doi:10.1038/srep02070 · Cited by 120 · see citing works
Sans, C. L., Satterwhite, D. J., Stoltzman, C. A., Breen, K., & Ayer, D. E. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00657-05 · Cited by 117 · see citing works
Identification of the Axin and Frat Binding Region of Glycogen Synthase Kinase-3
Fraser, E., Young, N., Dajani, R. B., Franca‐Koh, J., Ryves, J., Williams, R. S. B., Yeo, M., Webster, M.-T., Richardson, C. D., Smalley, M. J., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109462200 · Cited by 114 · see citing works
GJEDDE, A. H., & Marrett, S. (2001) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200112000-00002 · Cited by 112 · see citing works
Nehlig, A., Wittendorp-Rechenmann, E., & Dao Lam, C. (2004) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000128533.84196.d8 · Cited by 111 · see citing works
Hyperinsulinemia Induces Insulin Resistance in Dorsal Root Ganglion Neurons
Kim, B., McLean, L. L., Philip, S., & Feldman, E. L. (2011) · Endocrinology · doi:10.1210/en.2011-0029 · Cited by 107 · see citing works
Wang, J., & Kelly, P. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.0407a.x · Cited by 105 · see citing works
A Prospective Analysis of Elevated Fasting Glucose Levels and Cognitive Function in Older People
Euser, S. M., Sattar, N. A., Witteman, J. C. M., Bollen, E. L. E. M., Sijbrands, E. J. G., Albert Hofman, D., Perry, I. J., Breteler, M. M. B., Westendorp, R. G. J., & Study, F. P. A. T. R. (2010) · Diabetes · doi:10.2337/db09-0568 · Cited by 89 · see citing works
ATM is activated by ATP depletion and modulates mitochondrial function through NRF1
Chow, H., Cheng, A., Song, X., Swerdel, M. R., Hart, R. P., & Herrup, K. (2019) · The Journal of Cell Biology · doi:10.1083/jcb.201806197 · Cited by 82 · see citing works
Self-citationPenetration of peripheral glucose and insulin into cerebrospinal fluid in rats
Steffens, A. B., Scheurink, A. J. W., Porte, D., & Woods, S. C. (1988) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1988.255.2.r200 · Cited by 80 · see citing works
Esteve, P., Rueda‐Carrasco, J., Mateo, M. I., Martín‐Bermejo, M. J., Draffin, J. E., Pereyra, G., Sandonís, Á., Crespo, I., Moreno, I., Aso, E., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0432-1 · Cited by 78 · see citing works
Role of the SIK2–p35–PJA2 complex in pancreatic β-cell functional compensation
Sakamaki, J.-I., Fu, A., Reeks, C., Baird, S. D., Depatie, C., Azzabi, M. A., Bardeesy, N. M., Gingras, A., Yee, S., & Screaton, R. A. (2014) · Nature Cell Biology · doi:10.1038/ncb2919 · Cited by 77 · see citing works
CDK5 activator protein p25 preferentially binds and activates GSK3β
Chow, H., Guo, D. S., Zhou, J., Zhang, G.-Y., Li, H., Herrup, K., & Zhang, J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402627111 · Cited by 73 · see citing works
Self-citationWang, J., & Stelzer, A. (1996) · Journal of Neurophysiology · doi:10.1152/jn.1996.75.4.1687 · Cited by 65 · see citing works
Wang, J., Wei, J. N., Chen, X., Yu, J., Chen, N., & Shi, J. J. (2008) · Journal of Cell Science · doi:10.1242/jcs.025684 · Cited by 65 · see citing works
Wei, J. N., Zhang, M., Zhu, Y., & Wang, J. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.05.056 · Cited by 61 · see citing works
Lalioti, V. S., Muruáis, G., Dinarina, A., Damme, J. V., Vandekerckhove, J. S., & Sandoval, I. V. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900218106 · Cited by 59 · see citing works
Chen, L., LYU, J., Yang, X., Ji, W., Yuan, B.-X., Chen, M., Ma, X., & Wang, B. (2013) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2013.1453 · Cited by 49 · see citing works
Perez‐Leighton, C. E., Boland, K., Billington, C. J., & Kotz, C. M. (2013) · Obesity · doi:10.1002/oby.20045 · Cited by 39 · see citing works
Lutski, M., Weinstein, G., Goldbourt, U., & Tanné, D. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161016 · Cited by 37 · see citing works
Begg, D. P., May-Zhang, A. A., Mul, J. D., Liu, M., D’Alessio, D. A., Seeley, R. J., & Woods, S. C. (2015) · Diabetes · doi:10.2337/db14-1364 · Cited by 31 · see citing works
Cyclin-dependent Kinase-5 Is a Key Molecule in Tumor Necrosis Factor-α-induced Insulin Resistance
Nohara, A., Okada, S., Ohshima, K., Pessin, J. E., & Mori, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.231431 · Cited by 28 · see citing works
Wnt signaling and senescence: A tug of war in early neoplasia?
Adams, P. D., & Enders, G. H. (2008) · Cancer Biology & Therapy · doi:10.4161/cbt.7.11.6943 · Cited by 23 · see citing works
Wang, J., & Zhang, M. J. (2004) · Brain Research · doi:10.1016/j.brainres.2004.01.025 · Cited by 18 · see citing works
Christensen, D. Z., Thomsen, M. S., & Mikkelsen, J. D. (2013) · Neurochemistry International · doi:10.1016/j.neuint.2013.04.002 · Cited by 17 · see citing works
Cell- and region-specific miR30-based gene knock-down with temporal control in the rat brain
Liu, B., Xu, H., Paton, J. F. R., & Kasparov, S. (2010) · BMC Molecular Biology · doi:10.1186/1471-2199-11-93 · Cited by 11 · see citing works
Role of the Sik2-p35-Pja2 Complex in Pancreatic Beta Cell Functional Compensation
Sakamaki, J.-I., Fu, A., Reeks, C., Depatie, C., Azzabi, M. A., Bardeesy, N. M., Gingras, A., Yee, S., & Screaton, R. A. (2013) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2013.08.020 · Cited by 9 · see citing works
Mayer, J., Reichart, G., Tokay, T., Lange, F., Baltrusch, S., Junghanß, C., Wolkenhauer, O., Jaster, R., Kunz, M., Tiedge, M., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0123863 · Cited by 8 · see citing works
ATM is activated by ATP depletion and modulates mitochondrial function through NRF1Preprint
Chow, H., Cheng, A., Song, X., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/414490 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer’s patients
Mertens, J., Herdy, J. R., Traxler, L., Schafer, S. T., Schlachetzki, J. C. M., Böhnke, L., Reid, D. A., Lee, H., Zangwill, D., Fernandes, D. P., et al. (2021) · Cell Stem Cell · doi:10.1016/j.stem.2021.04.004 · Cited by 240 · see citing works
Herdy, J. R., Traxler, L., Agarwal, R. K., Karbacher, L., Schlachetzki, J. C. M., Boehnke, L., Zangwill, D., Galasko, D., Glass, C. K., Mertens, J., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.11.010 · Cited by 208 · see citing works
Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce
Li, Q., Hagberg, C. E., Silva Cascales, H., Lang, S., Hyvönen, M. T., Salehzadeh, F., Chen, P., Alexandersson, I., Terezaki, E., Harms, M. J., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01501-8 · Cited by 178 · see citing works
Profiling senescent cells in human brains reveals neurons with CDKN2D/p19 and tau neuropathology
Dehkordi, S. K., Walker, J., Sah, E., Bennett, E., Atrian, F., Frost, B., Woost, B., Bennett, R. E., Orr, T. C., Zhou, Y., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00142-3 · Cited by 169 · see citing works
Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease
Welch, G., & Tsai, L. (2022) · The EMBO Reports · doi:10.15252/embr.202154217 · Cited by 129 · see citing works
Gaikwad, S., Senapati, S., Haque, M. A., & Kayed, R. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13490 · Cited by 117 · see citing works
Reading, C. L., Ahlem, C. N., & Murphy, M. F. (2021) · Neurodegenerative Disease Management · doi:10.2217/nmt-2021-0022 · Cited by 84 · see citing works
Role of glucagon-like peptide-1 receptor agonists in Alzheimer’s disease and Parkinson’s disease
Hong, C.-T., Chen, J.-H., & Hu, C.-J. (2024) · Journal of Biomedical Science · doi:10.1186/s12929-024-01090-x · Cited by 78 · see citing works
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Novotný, J., Čarná, M., Dammer, E., Mao, Z., & Stokin, G. (2025) · doi:10.1101/2025.11.27.690929 · Cited by 1 · see citing works
Kawabata, S., Iijima, H., Kanemura, N., & Murata, K. (2025) · Molecular Neurobiology · doi:10.1007/s12035-024-04666-8
- Authors
- Chow, H.-M., Shi, M., Cheng, A., Gao, Y., Chen, G., Song, X., So, R. W. L., Zhang, J., & Herrup, K.
- Affiliations
- Chinese University of Hong Kong (HK)
- Xiamen University (CN)
- Hong Kong University of Science and Technology (HK)
- University of Pittsburgh (US)
- Corresponding author
- Chow, Hei-Man
- Zhang, Jie
- Herrup, Karl
- Venue
- Nature Neuroscience
- Published
- 2019-10-21
- Volume
- 22
- Issue
- 11
- Pages
- 1806-1819
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2980373857
- Cited by
- 171
- References
- 66
- Citations by year
- 2026: 14 · 2025: 31 · 2024: 38 · 2023: 28 · 2022: 21 · 2021: 33 · 2020: 6
- FWCI
- 10.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- Research Grants Council, University Grants Committee (16100219, 16100718, 16103317, 660813, 16101315)
- Alzheimer’s Association (AARF-17-531566)
- National Natural Science Foundation of China (91849205)
- Fundamental Research Funds for Central Universities of China-Xiamen University
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- hyperinsulinemia, insulin resistance, neurons, neuronal senescence, prediabetes, Alzheimer's disease, cerebrospinal fluid insulin, hexokinase 2, glycolysis, cyclin-dependent kinase 5, GSK3β, β-catenin degradation, neuronal cell death, cognitive decline, age-related neurodegeneration
- MeSH terms
- Liraglutide, Aging, Animals, Cell Cycle, Glycolysis, Hexokinase, Hyperinsulinism, Insulin, Insulin Resistance, Male, Metformin, Neurons, Phosphotransferases, Gene Expression, Cellular Senescence, Cell Death, Protein Serine-Threonine Kinases, Maze Learning, Excitatory Postsynaptic Potentials, beta Catenin, Cyclin-Dependent Kinase 5, Mice, Inhibitory Postsynaptic Potentials, Ubiquitination, Primary Cell Culture
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