Diet Restriction Slows Neurodegeneration and Extends Lifespan of DNA-Repair-Deficient Mice

DNA damage occurs in human cells at a constant rate. These cells are usually able to repair themselves, but sometimes deficiencies in certain genes cause the repair process to shut down. When damaged DNA isn’t fixed, mutations can occur that cause accelerated aging or cancerous tumors to form (Hoeijmakers, 2009). Scientists at Erasmus University Medical Center in Rotterdam have found a way to slow down the process – at least in mice.

In a study published in Nature, the researchers report that when mice deficient in the DNA-repair genes Ercc1 or Xpg are put on a restricted diet, they experience better overall health and increased lifespans compared to DNA-repair-deficient mice fed a normal diet. They also found significantly lower levels of neurodegeneration in the brains and spinal cords of diet restricted animals compared to controls.

“Here we report that a dietary restriction of 30 percent tripled the median and maximal remaining lifespans of these progeroid mice, strongly retarding numerous aspects of accelerated aging Mice undergoing dietary restriction retained 50 percent more neurons and maintained full motor function far beyond the lifespan of mice fed ad libitum,” (Vermeij, et al 2016).

Since the DNA-repair-deficient mice were already smaller and weaker than normal mice, the Rotterdam researchers wondered whether diet restriction would be beneficial or detrimental to their health. They found that gradually restricting the diets of DNA-repair-deficient mice starting at age seven weeks increased their median lifespans from 10 to 35 weeks in males and 13 to 39 weeks in females as compared to controls.

They also saw significant differences in the levels of neurodegeneration between these two populations. Using Stereo Investigator, they found 50 percent more neurons in the brains of diet-restricted mice compared to those fed a normal diet. They also saw lower levels of cells expressing p53 – a protein expressed in response to DNA damage – in diet-restricted mice.

According to the authors, dietary restriction may not fix defects in DNA repair mechanisms, but it may help to reduce the severity and speed at which the damage occurs.

“Our findings establish the Ercc1 mouse as a powerful model organism for health-sustaining interventions, reveal potential for reducing endogenous DNA damage, facilitate a better understanding of the molecular mechanism of dietary restriction and suggest a role for counterintuitive dietary-restriction-like therapy for human progeroid genome instability syndromes and possibly neurodegeneration in general,” (Vermeij, et al 2016).

Vermeij W.P., Dollé M.E.T., Reiling E., Jaarsma D., Payan-Gomez C, Bombardieri C.R., Wu H., Roks A.J.M., Botter S.M., van der Eerden B.C., Youssef S.A., Kuiper R.V., Nagarajah B., van Oostrom C.T., Brandt R.M.C., Barnhoorn S., Imholz S., Pennings J.L.A., de Bruin A., Gyenis Á., Pothof J, Vijg J, van Steeg H., and Hoeijmakers J.H.J. (2016) Restricted diet delays accelerated aging and genomic stress in DNA repair deficient mice. Nature 537, 427-431, doi:10.1038/nature19329

Hoeijmakers JH (2009) DNA Damage, aging, and cancer. N Engl J Med; 361:1475-1485, DOI: 10.1056/NEJMra0804615

Stock image of DNA used in accordance with the CC0 public domain license.

Researchers cited MBF Bioscience systems in 27 papers between 08/18/2017 and 09/01/2017

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Researchers cited MBF Bioscience systems in 32 papers between 08/11/2017 and 08/18/2017

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Researchers cited MBF systems in 8 papers during the week of 06/19/2017

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Martinez, E. M., Young, A. L., Patankar, Y. R., Berwin, B. L., Wang, L., von Herrmann, K. M., . . . Havrda, M. C. (2017). Nlrp3 is required for inflammatory changes and nigral cell loss resulting from chronic intragastric rotenone exposure in mice. Toxicological Sciences. https://academic.oup.com/toxsci/article-abstract/doi/10.1093/toxsci/kfx1…

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Researchers cited MBF systems in 25 papers between 6/10/2017 and 6/16/2017

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Arawaka, S., Sato, H., Sasaki, A., Koyama, S., & Kato, T. (2017). Mechanisms underlying extensive Ser129-phosphorylation in α-synuclein aggregates. Acta Neuropathologica Communications, 5(1), 48.

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Chaves, P. P., Valdoria, C. M., Amorim, M. C. P., & Vasconcelos, R. O. (2017). Ontogenetic development of the inner ear saccule and utricle in the Lusitanian toadfish: Potential implications for auditory sensitivity. Hearing Research. doi: https://doi.org/10.1016/j.heares.2017.06.008.

Ebenezer, G. J., Liu, Y., Judge, D. P., Cunningham, K., Truelove, S., Carter, N. D., . . . Polydefkis, M. (2017). Cutaneous nerve biomarkers in transthyretin familial amyloid polyneuropathy. Annals of Neurology, n/a-n/a. doi: 10.1002/ana.24972.

Fischer, D. L., Kemp, C. J., Cole-Strauss, A., Polinski, N. K., Paumier, K. L., Lipton, J. W., . . . Sortwell, C. E. (2017). Subthalamic Nucleus Deep Brain Stimulation Employs TrkB Signaling for Neuroprotection and Functional Restoration. The Journal of Neuroscience.

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Researchers cited MBF systems in 25 papers between 5/27/2017 and 6/9/2017

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Bastidas, J., Athauda, G., De La Cruz, G., Chan, W.-M., Golshani, R., Berrocal, Y., . . . Pearse, D. D. (2017). Human schwann cells exhibit long-term cell survival, are not tumorigenic and promote repair when transplanted into the contused spinal cord. Glia, n/a-n/a. doi: 10.1002/glia.23161.

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Researchers cited MBF systems in 25 papers between 5/16/2017 and 5/26/2017

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Baxter, V. K., Glowinski, R., Braxton, A. M., Potter, M. C., Slusher, B. S., & Griffin, D. E. (2017). Glutamine antagonist-mediated immune suppression decreases pathology but delays virus clearance in mice during nonfatal alphavirus encephalomyelitis. Virology, 508, 134-149. doi: https://doi.org/10.1016/j.virol.2017.05.013.

Brzozowska, N. I., Smith, K. L., Zhou, C., Waters, P. M., Cavalcante, L. M., Abelev, S. V., . . . Arnold, J. C. (2017). Genetic deletion of P-glycoprotein alters stress responsivity and increases depression-like behavior, social withdrawal and microglial activation in the hippocampus of female mice. Brain, Behavior, and Immunity. doi: https://doi.org/10.1016/j.bbi.2017.05.008.

Chareyron, L. J., Banta Lavenex, P., Amaral, D. G., & Lavenex, P. (2017). Functional organization of the medial temporal lobe memory system following neonatal hippocampal lesion in rhesus monkeys. Brain Structure and Function, 1-16. doi: 10.1007/s00429-017-1441-z.

Kwan, T., Floyd, C. L., Patel, J., Mohaimany-Aponte, A., & King, P. H. (2017). Astrocytic expression of the RNA regulator HuR accentuates spinal cord injury in the acute phase. Neuroscience Letters, 651, 140-145. doi: https://doi.org/10.1016/j.neulet.2017.05.003.

Newville, J., Valenzuela, C. F., Li, L., Jantzie, L. L., & Cunningham, L. A. (2017). Acute oligodendrocyte loss with persistent white matter injury in a third trimester equivalent mouse model of fetal alcohol spectrum disorder. Glia, n/a-n/a. doi: 10.1002/glia.23164.

Onger, M. E., Kaplan, S., Geuna, S., Türkmen, A. P., Muratori, L., Altun, G., & Altunkaynak, B. Z. (2017). Possible effects of some agents on the injured nerve in obese rats: A stereological and electron microscopic study. Journal of Cranio-Maxillofacial Surgery. doi: https://doi.org/10.1016/j.jcms.2017.05.004.

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Researchers cited MBF systems in 17 papers during the week of 05/08/2017

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Day, N. L., Carle, M. S., & Floyd, C. L. (2017). Post-injury administration of a combination of memantine and 17β-estradiol is protective in a rat model of traumatic brain injury. Neurochemistry International. doi: https://doi.org/10.1016/j.neuint.2017.04.018.

El-Agnaf, O., Overk, C., Rockenstein, E., Mante, M., Florio, J., Adame, A., . . . Rissman, R. A. (2017). Differential effects of immunotherapy with antibodies targeting α-synuclein oligomers and fibrils in a transgenic model of synucleinopathy. Neurobiology of Disease, 104, 85-96. doi: https://doi.org/10.1016/j.nbd.2017.05.002.

Matsuda, W., Ehara, A., Nakadate, K., Yoshimoto, K., & Ueda, S. (2017). Effects of environmental enrichment on the activity of the amygdala in micrencephalic rats exposed to a novel open field. Congenital Anomalies, n/a-n/a. doi: 10.1111/cga.12228.

Musacchio, T., Rebenstorff, M., Fluri, F., Brotchie, J. M., Volkmann, J., Koprich, J. B., & Ip, C. W. (2017). STN-DBS is neuroprotective in the A53T α-synuclein Parkinson’s disease rat model. Annals of Neurology, n/a-n/a. doi: 10.1002/ana.24947.

Soares, J. I., Valente, M. C., Andrade, P. A., Maia, G. H., & Lukoyanov, N. V. (2017). Reorganization of the septohippocampal cholinergic fiber system in experimental epilepsy. Journal of Comparative Neurology, n/a-n/a. doi: 10.1002/cne.24235.

Yoshii, Y., Inoue, T., Uemura, Y., Iwasaki, Y., Yada, T., Nakabeppu, Y., & Noda, M. (2017). Complexity of Stomach–Brain Interaction Induced by Molecular Hydrogen in Parkinson’s Disease Model Mice. Neurochemical Research, 1-8. doi: 10.1007/s11064-017-2281-1.  Continue reading “Researchers cited MBF systems in 17 papers during the week of 05/08/2017” »

Researchers cited MBF systems in 42 papers between 4/7/2017 and 4/21/2017

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Ay, M., Luo, J., Langley, M., Jin, H., Anantharam, V., Kanthasamy, A., & Kanthasamy, A. G. (2017). Molecular Mechanisms Underlying Protective Effects of Quercetin Against Mitochondrial Dysfunction and Progressive Dopaminergic Neurodegeneration in Cell Culture and MitoPark Transgenic Mouse Models of Parkinson’s Disease. Journal of Neurochemistry, n/a-n/a. doi: 10.1111/jnc.14033.

Carryl, H., Van Rompay, K., De Paris, K., & Burke, M. (2017). Hippocampal Neuronal Loss in Infant Macaques Orally Infected with Virulent Simian Immunodeficiency Virus (SIV). Brain Sciences, 7(4), 40.

Galinato, M. H., Lockner, J. W., Fannon-Pavlich, M. J., Sobieraj, J. C., Staples, M. C., Somkuwar, S. S., . . . Mandyam, C. D. (2017). A synthetic small-molecule Isoxazole-9 protects against methamphetamine relapse. Molecular Psychiatry. doi: 10.1038/mp.2017.46.

Gilles, Y. D., & Polston, E. K. (2017). Effects of social deprivation on social and depressive-like behaviors and the numbers of oxytocin expressing neurons in rats. Behavioural Brain Research SreeTestContent1, 328, 28-38. doi: http://doi.org/10.1016/j.bbr.2017.03.036.

Hamilton, G. F., Hernandez, I. J., Krebs, C. P., Bucko, P. J., & Rhodes, J. S. (2017). Neonatal alcohol exposure reduces number of parvalbumin-positive interneurons in the medial prefrontal cortex and impairs passive avoidance acquisition in mice deficits not rescued from exercise. Neuroscience. doi: http://doi.org/10.1016/j.neuroscience.2017.03.058.

Jinhua, H., Zhao, M., Shuangcheng, H., Yuanran, Z., Rui, N., Wei, L., . . . Jian, Y. (2017). Icariin protects against glucocorticoid induced osteoporosis, increases the expression of the bone enhancer DEC1 and modulates the PI3K/Akt/GSK3β/β-catenin integrated signaling pathway. Biochemical Pharmacology. doi: http://doi.org/10.1016/j.bcp.2017.04.010.

Kafetzopoulos, V., Kokras, N., Sotiropoulos, I., Oliveira, J. F., Leite-Almeida, H., Vasalou, A., . . . Dalla, C. (2017). The nucleus reuniens: a key node in the neurocircuitry of stress and depression. Molecular Psychiatry. doi: 10.1038/mp.2017.55.

Lear, C. A., Davidson, J. O., Mackay, G. R., Drury, P. P., Galinsky, R., Quaedackers, J. S., . . . Bennet, L. (2017). Antenatal dexamethasone before asphyxia promotes cystic neural injury in preterm fetal sheep by inducing hyperglycemia. Journal of Cerebral Blood Flow and Metabolism, 0271678X17703124. doi: 10.1177/0271678×17703124.

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Researchers cited MBF systems in 27 papers between 3/20/2017 and 3/30/2017

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Abe, C., Inoue, T., Inglis, M. A., Viar, K. E., Huang, L., Ye, H., . . . Guyenet, P. G. (2017). C1 neurons mediate a stress-induced anti-inflammatory reflex in mice. Nature Neuroscience, advance online publication. doi: 10.1038/nn.4526

Caldwell, A. S. L., Edwards, M. C., Desai, R., Jimenez, M., Gilchrist, R. B., Handelsman, D. J., & Walters, K. A. (2017). Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome. Proceedings of the National Academy of Sciences. doi: 10.1073/pnas.1616467114.

Castro-Hernández, J., Adlard, P. A., & Finkelstein, D. I. (2017). Pramipexole restores depressed transmission in the ventral hippocampus following MPTP-lesion. Scientific Reports, 7, 44426. doi: 10.1038/srep44426.

Dawes, W. J., Zhang, X., Fancy, S. P., Rowitch, D., & Marino, S. (2017). Moderate-Grade Germinal Matrix Haemorrhage Activates Cell Division in the Neonatal Mouse Subventricular Zone. Developmental Neuroscience.

Drobyshevsky, A., & Quinlan, K. A. (2017). Spinal cord injury in hypertonic newborns after antenatal hypoxia-ischemia in a rabbit model of cerebral palsy. Experimental Neurology, 293, 13-26. doi: http://dx.doi.org/10.1016/j.expneurol.2017.03.017.

El Massri, N., Lemgruber, A. P., Rowe, I. J., Moro, C., Torres, N., Reinhart, F., . . . Mitrofanis, J. (2017). Photobiomodulation-induced changes in a monkey model of Parkinson’s disease: changes in tyrosine hydroxylase cells and GDNF expression in the striatum. Experimental Brain Research, 1-14. doi: 10.1007/s00221-017-4937-0.

Hühner, L., Rilka, J., Gilsbach, R., Zhou, X., Machado, V., & Spittau, B. (2017). Interleukin-4 Protects Dopaminergic Neurons In vitro but Is Dispensable for MPTP-Induced Neurodegeneration In vivo. Frontiers in Molecular Neuroscience, 10(62). doi: 10.3389/fnmol.2017.00062.

Meng, L., Huang, T., Sun, C., Hill, D. L., & Krimm, R. (2017). BDNF is required for taste axon regeneration following unilateral chorda tympani nerve section. Experimental Neurology, 293, 27-42. doi: http://dx.doi.org/10.1016/j.expneurol.2017.03.016.

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