Review
BibTex RIS Cite

BEYİN YAŞLANMASINDA MOLEKÜLER MEKANİZMALAR

Year 2023, , 284 - 294, 20.01.2023
https://doi.org/10.33483/jfpau.1099963

Abstract

Amaç: Bu derlemede beyinde yaşlanmayla birlikte oluşan moleküler değişimlerin anlatılması amaçlanmıştır. Beyin yaşlanmasının moleküler mekanizmaları; oksidatif stres, mitokondriyal disfonksiyon, endoplazmik retikulum stres, otofaji, inflamasyon, lizozom ve proteazom işlevinin bozulması, bozulmuş DNA onarımı başlıkları altında toplanmış ve bu konulara odaklanılmıştır.
Sonuç ve Tartışma: Yaşlanma, muhtemelen organizmalardaki hasar birikiminden ve/veya bakım ve onarım mekanizmalarındaki düşüşten kaynaklanan çok faktörlü bir süreçtir. Yaşlanmayla birlikte beyinde de yapısal ve fonksiyonel birçok değişim meydana gelmektedir. Bu değişiklikler nörodejeneratif bozukluklarla birlikte Alzheimer, Parkinson gibi hastalıklara yatkınlık oluşturmaktadır. Beyin yaşlandığında öğrenme, karar verme, hafıza gibi yeteneklerinde azalmalar görülmektedir. Beyin yaşlanmasına bağlı hastalıklara ve fonksiyonel bozukluklara karşı terapötik veya koruyucu yaklaşımlar geliştirmek için beyin yaşlanmasının moleküler düzeydeki mekanizmalarının aydınlatılmasına ihtiyaç vardır.

References

  • 1. Mattson, M.P., Arumugam T.V. (2018). Hallmarks of brain aging: adaptive and pathological modification by metabolic states. Cell Metabolism, 27(6), 1176–1199. [CrossRef]
  • 2. Alexander, G.E., Ryan, L., Bowers, D., Foster, T.C., Bizon, J.L., Geldmacher, D.S., Glisky, E.L. (2012). Characterizing cognitive aging in humans with links to animal models. Frontiers in Aging Neuroscience, 4, 21. [CrossRef]
  • 3. Dykiert, D., Der, G., Starr, J.M., Deary, I.J. (2012). Age differences in intra-individual variability in simple and choice reaction time: systematic review and meta-analysis. PLoS One, 7(10), e45759. [CrossRef]
  • 4. Levin, O., Fujiyama, H., Boisgontier, M.P., Swinnen, S.P., Summers, J.J. (2014). Aging and motor inhibition: a converging perspective provided by brain stimulation and imaging approaches. Neuroscience and Biobehavioral Reviews, 43, 100-117. [CrossRef]
  • 5. Aarsland, D., Creese, B., Politis, M., Chaudhuri, K.R., Ffytche, D.H., Weintraub, D., Ballard, C. (2017). Cognitive decline in parkinson disease. Nature Reviews Neurology, 13(4), 217-231. [CrossRef]
  • 6. Kalia, L. V., Lang, A. E. (2015). Parkinson's disease. Lancet, 386(9996), 896-912. [CrossRef]
  • 7. Mattson, M.P. (2004). Pathways towards and away from alzheimer's disease. Nature, 430(7000), 631-639. [CrossRef]
  • 8. Scheltens, P., Blennow, K., Breteler, M.M., de Strooper, B., Frisoni, G.B., Salloway, S., Van der Flier, W.M. (2016). Alzheimer's disease. Lancet, 388(10043), 505-517. [CrossRef]
  • 9. Isaev, N.K., Stelmashook, E.V., Stelmashook, N.N., Sharonova, I.N., Skrebitsky, V.G. (2013). Brain aging and mitochondria-targeted plastoquinone antioxidants of SkQ-type. Biochemistry (Mosc), 78(3), 295-300. [CrossRef]
  • 10. Isaev, N.K., Stelmashook, E.V., Genrikhs, E.E. (2019). Neurogenesis and brain aging. Rev Neurosci, 30(6), 573-580. [CrossRef]
  • 11. Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., Gargiulo, G., Testa, G., Cacciatore, F., Bonaduce, D., Abete, P. (2018). Oxidative stress, aging, and diseases. Clinical Interventions in Aging., 13, 757-72. [CrossRef]
  • 12. Ionescu-Tucker, A., Cotman, C.W. (2021). Emerging roles of oxidative stress in brain aging and alzheimer’s disease. Neurobiology of Aging., 107, 86-95. [CrossRef]
  • 13. Butterfield, D.A., Howard, B.J., LaFontaine, M.A. (2001). Brain oxidative stress in animal models of accelerated aging and the age-related neurodegenerative disorders, alzheimer’s disease and huntington’s disease. Current Medicinal Chemistry, 8(7), 815-28. [CrossRef]
  • 14. Zhang, Y., Ding, C., Cai, Y., Chen, X., Zhao, Y., Liu, X., Zhang, J., Sun, S., Liu, W. (2021). Astilbin ameliorates oxidative stress and apoptosis in D-galactose-induced senescence by regulating the PI3K/Akt/m-TOR signaling pathway in the brains of mice. International Immunopharmacology, 99, 108035. [CrossRef]
  • 15. Aydın, A.F., Çoban, J., Doğan-Ekici, I., Betül-Kalaz, E., Doğru-Abbasoğlu, S., Uysal, M.(2016). Carnosine and taurine treatments diminished brain oxidative stress and apoptosis in D-galactose aging model. Metabolic Brain Disease, 31(2), 337-45. [CrossRef]
  • 16. Singh, S., Singh, A.K., Garg, G., Rizvi, S.I.(2018). Fisetin as a caloric restriction mimetic protects rat brain against aging induced oxidative stress, apoptosis and neurodegeneration. Life Sciences, 193, 171-179. [CrossRef]
  • 17. Garg, G., Singh, S., Singh, A.K., Rizvi, S.I. (2018). N-acetyl-l-cysteine attenuates oxidative damage and neurodegeneration in rat brain during aging. Canadian Journal of Physiology and Pharmacology, 96(12), 1189-1196. [CrossRef]
  • 18. Wan, J.Z., Wang, R., Zhou, Z.Y., Deng, L.L., Zhang, C.C., Liu, C.Q., Zhao, H.X., Yuan, C.F., He, Y.M., Dun, Y.Y., Yuuan, D., Wang, T. (2020). Saponins of panax japonicus confer neuroprotection against brain aging through mitochondrial related oxidative stress and autophagy in rats. Current Pharmaceutical Biotechnology, 21(8), 667-680. [CrossRef]
  • 19. Yang, C., DeMars, K.M., Candelario-Jalil, E. (2018). Age-dependent decrease in adropin is associated with reduced levels of endothelial nitric oxide synthase and increased oxidative stress in the rat brain. Aging and Disease, 9(2), 322-330. [CrossRef]
  • 20. Alabarse, P.V.G., Hackenhaar, F.S., Medeiros, T.M., Mendes, M.F.A., Viacava, P.R., Schüller, A.K., Salomon, T.B., Ehrenbrink, G., Benfato, M.S. (2011). Oxidative stress in the brain of reproductive male rats during aging. Experimental Gerontology, 46(4), 241-8. [CrossRef]
  • 21. Li, X., Chen, Y., Shao, S., Tang, Q., Chen, W., Chen, Y., Xu, X. (2016). Oxidative stress induces the decline of brain EPO expression in aging rats. Experimental Gerontology, 83, 89-93. [CrossRef]
  • 22. Tatarkova , Z., Kovalska , M., Timkova, V., Racay,P., Lehotsky, J., Kaplan, P. (2016). The effect of aging on mitochondrial complex I and the extent of oxidative stress in the rat brain cortex. Neurochemical Research, 41(8), 2160-72. [CrossRef]
  • 23. Navarro, A., Boveris, A. (2010). Brain mitochondrial dysfunction in aging, neurodegeneration, and parkinson's disease. Frontiers in Aging Neuroscience, 2, 34. [CrossRef]
  • 24. Leuner, K., Hauptmann, S., Abdel-Kader, R., Scherping, I., Keil, U., Strosznajder, J.B., Eckert, A., Müller, W. E. (2007). Mitochondrial dysfunction: the first domino in brain aging and alzheimer's disease? Antioxid Redox Signal., 9(10), 1659-75. [CrossRef]
  • 25. Liu, H., Zhang, X., Xiao, J., Song, M., Cao, Y., Xiao, H., Liu, X. (2020). Astaxanthin attenuates d-galactose-induced brain aging in rats by ameliorating oxidative stress, mitochondrial dysfunction, and regulating metabolic markers. Food and Function, 11(5), 4103-4113. [CrossRef]
  • 26. Boveris, A., Navarro, A. (2008). Brain mitochondrial dysfunction in aging. IUBMB Life, 60(5), 308-14. [CrossRef]
  • 27. Li, Y., Yu, H., Chen, C., Li, S., Zhang, Z., Xu, H., Zhu, F., Liu, J., Spencer, P.S., Dai, Z., Yang, X. (2020). Proteomic profile of mouse brain aging contributions to mitochondrial dysfunction, DNA oxidative damage, loss of neurotrophic factor, and synaptic and ribosomal proteins. Oxidative Medicine Cellular Longevity, 5408452. [CrossRef]
  • 28. Gauba, E., Guo, L., Du, H. (2017). Cyclophilin D promotes brain mitochondrial F1FO ATP synthase dysfunction in aging mice. Journal of Alzheimer's Disease, 55(4), 1351-1362. [CrossRef]
  • 29. Klosinski, L.P., Yao, J., Yin, F., Fonteh, A.N., Harrington, M.G., Christensen, T.A., Trushina, E., Brinton, R.D. (2015). White matter lipids as a ketogenic fuel supply in aging female brain: implications for alzheimer's disease. EbioMedicine, 2(12), 1888-904. [CrossRef]
  • 30. Brown, M.K., Naidoo, N. (2012). The endoplasmic reticulum stress response in aging and age-related diseases. Frontiers in Physiology, 3, 263. [CrossRef]
  • 31. Anelli, T., Sitia, R. (2008). Protein quality control in the early secretory pathway.The EMBO Journal, 27(2), 315-27. [CrossRef]
  • 32. Oakes, S.A., Papa, F.R. (2015). The role of endoplasmic reticulum stress in human pathology. Annual Review of Pathology, 10, 173-94. [CrossRef]
  • 33. Wang, S., Kaufman, R. J. (2012). The impact of the unfolded protein response on human disease. The Journal of Cell Biology, 197(7), 857-67. [CrossRef]
  • 34. Bertolotti, A., Zhang, Y., Hendershot, L.M., Harding, H.P., Ron, D. (2000). Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nature Cell Biology, 2(6), 326-32. [CrossRef]
  • 35. Ma, K., Vattem, K.M., Wek, R.C. (2002). Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stress. The Journal of Biological Chemistry, 277(21), 18728-35. [CrossRef]
  • 36. Shen, J., Linda, X.C., Hendershot, L., Prywes, R. (2002). ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of golgi localization signals. Developmental Cell, 3(1), 99-111. [CrossRef]
  • 37. Oakes, S. A. (2020). Endoplasmic reticulum stress signaling in cancer cells. The American Journal of Pathology, 190(5), 934-946. [CrossRef]
  • 38. Taylor, R.C. (2016). Aging and the UPR(ER). Brain Research, 1648, 588-593. [CrossRef]
  • 39. Oh, J.H., Nam, T.J. (2019). Hydrophilic glycoproteins of an edible green alga capsosiphon fulvescens prevent aging-induced spatial memory impairment by suppressing GSK-3β-Mediated ER stress in dorsal hippocampus. Marine Drugs, 17(3), 168. [CrossRef]
  • 40. Naidoo, N, Ferber, M., Master, M., Zhu, Y., Pack, A.I. (2008). Aging impairs the unfolded protein response to sleep deprivation and leads to proapoptotic signaling. The Journal of Neuroscience, 28(26), 6539-48. [CrossRef]
  • 41. Naidoo, N., Zhu, J., Galante, R.J., Lian, J., Strus, E., Lee, A., Keenan, B.T., Pack, A.I. (2018). Reduction of the molecular chaperone binding immunoglobulin protein (BiP) accentuates the effect of aging on sleep-wake behavior. Neurobiology of Aging, 69, 10-25. [CrossRef]
  • 42. Hussain, S.G., Ramaiah, K.V. (2007). Reduced eIF2alpha phosphorylation and increased proapoptotic proteins in aging. Biochemical Biophysical Research Communications, 355, 365-370. [CrossRef]
  • 43. Plaza-Zabala, A., Sierra-Torre, V., Sierra, A. (2017). Autophagy and microglia: novel partners in neurodegeneration and aging. International Journal of Molecular Sciences, 18(3), 598. [CrossRef]
  • 44. Loeffler, D.A. (2019). Influence of normal aging on brain autophagy: a complex scenario. Frontiers in Aging Neuroscience, 11, 49. [CrossRef]
  • 45. Liu, A.D., Guo, E.S., Yang, J.K., Yang, Y., Liu, S.P., Jiang, X.J., Hu, Q., Dirsch, O., Dahmen, U., Zhang, C.T., Gewirtz, D.A., Fang, H.S. (2018). Young plasma reverses age-dependent alterations in hepatic function through the restoration of autophagy. Aging Cell, 17(1), e12708. [CrossRef]
  • 46. LaRocca, T.J., Henson, G.D., Thorburn, A., Sindler, A.L., Pierce, G.L., Seals, D.R. (2012). Translational evidence that impaired autophagy contributes to arterial ageing. Journal of Physiology-London, 590, 3305-3316. [CrossRef]
  • 47. LaRocca, T.J., Gioscia-Ryan, R.A., Hearon, C.M., Seals, D.R. (2013). The autophagy enhancer spermidine reverses arterial aging. Mechanisms of Ageing and Development, 134, 314-320. [CrossRef]
  • 48. Cao Y., Klionsky D.J. (2007). Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein. Cell Research, 17, 839–849. [CrossRef]
  • 49. Mizushima N., Yoshimori T., Levine B. (2010). Methods in mammalian autophagy research. Cell, 140, 313– 326. [CrossRef]
  • 50. Shen, K., Liu, X., Chen, D., Chang, J., Zhang, Y., Kou, X. (2021). Voluntary wheel-running exercise attenuates brain aging of rats through activating miR-130a-mediated autophagy. Brain Research Bulletin, 172, 203-211. [CrossRef]
  • 51. Cervellati, C., Trentini, A., Pecorelli, A., Valacchi, G. (2020). Inflammation in neurological disorders: the thin boundary between brain and periphery. Antioxidants Redox Signaling, 33(3), 191-210. [CrossRef]
  • 52. Aguzzi, A., Barres, B.A., Bennett, M.L.(2013). Microglia: scapegoat, saboteur, or something else? Science, 339(6116), 156-61. [CrossRef]
  • 53. Cribbs, D.H., Berchtold N.C., Perreau V., Coleman P.D., Rogers J., Tenner A.J., Cotman C.W. (2012). Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study. Journal of Neuroinflammation, 9, 179. [CrossRef]
  • 54. Norden, D.M., Godbout J.P. (2013). Review: microglia of the aged brain: primed to be activated and resistant to regulation. Neuropathology and Applied Neurobiology, 39, 19–34. [CrossRef]
  • 55. Mosher K.I., Wyss-Coray T. (2014). Microglial dysfunction in brain aging and Alzheimer’s disease. Biochemical Pharmacology, 88, 594–604. [CrossRef]
  • 56. Marschallinger, J., Iram, T., Zardeneta, M., Lee, S.E., Lehallier, B., Haney, M.S., Pluvinage, J. V., Mathur, V., Hahn, O., Morgens, D.W., Kim, J., Tevini, J., Felder, T.K., Wolinski, H., Bertozzi, C.R., Bassik, M.C., Aigner, L., Wyss-Coray, T. (2020). Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain. Nature Neuroscience, 23(2), 194-208. [CrossRef]
  • 57. Elahi, F.M., Harvey, D., Altendahl, M., Brathaban, N., Fernandes, N., Casaletto, K.B., Staffaroni, A.M., Maillard, P., Hinman, J.D., Miller, B.L., DeCarli, C., Kramer, J.H., Goetzl, E.J.(2021). Elevated complement mediator levels in endothelial-derived plasma exosomes implicate endothelial innate inflammation in diminished brain function of aging humans. Scientifik Reports, 11(1), 16198. [CrossRef]
  • 58. Corlier, F., Hafzalla, G., Faskowitz, J., Kuller, L.H., Becker, J.T., Lopez, O.L., Thompson, P.M., Braskie, M.N. (2018). Systemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk. Neuroimage, 172, 118-129. [CrossRef]
  • 59. Sala-Llonch, R., Idland, A.V., Borza, T., Watne, L.O., Wyller, T.B., Brækhus, A., Zetterberg, H., Blennow, K., Walhovd, K.B., Fjell, A.M. (2017). Inflammation, amyloid, and atrophy in the aging brain: relationships with longitudinal changes in cognition. Journal of Alzheimer’s Disease, 58(3), 829-840. [CrossRef]
  • 60. Lindbergh, C.A., Casaletto, K.B., Staffaroni, A.M., Elahi, F., Walters, S.M., You, M., Neuhaus, J., Rivera Contreras, W., Wang, P., Karydas, A., Brown, J., Wolf, A., Rosen, H., Cobigo, Y., Kramer, J.H. (2020). Systemic tumor necrosis factor-alpha trajectories relate to brain health in typically aging older adults. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 75, 1558-1565. [CrossRef]
  • 61. Spencer, S.J., D'Angelo, H., Soch, A., Watkins, L.R., Maier, S.F., Barrientos, R.M. (2017). High-fat diet and aging interact to produce neuroinflammation and impair hippocampal- and amygdalar-dependent memory. Neurobiology of Aging, 58, 88-101. [CrossRef]
  • 62. Keller, J.N., Dimayuga, E., Chen, Q., Thorpe, J., Gee, J., Ding, Q. (2004). Autophagy, proteasomes, lipofuscin, and oxidative stress in the aging brain. The International Journal of Biochemistry Cell Biology, 36(12), 2376-91 [CrossRef]
  • 63. Farout, L., Friguet, B. (2006). Proteasome function in aging and oxidative stress: implications in protein maintenance failure. Antioxidants Redox Signaling, 8(1-2), 205-16. [CrossRef]
  • 64. Kukan, M. (2004). Emerging roles of proteasomes in ischemia-reperfusion injury of organs. Journal of Physiology and Pharmacology, 55(1 Pt 1), 3-15. [CrossRef]
  • 65. Sun-Wang, J. L., Ivanova, S., Zorzano, A. (2020). The dialogue between the ubiquitin-proteasome system and autophagy: Implications in ageing. Ageing Research Reviews, 64, 101203. [CrossRef]
  • 66. Eldeeb, M. A. (2021). N-Terminal-Dependent protein degradation and targeting cancer cells. Anticancer Agents in Medicinal Chemistry, 21(2), 231-236. [CrossRef]
  • 67. Cao, J., Zhong, M.B., Taro, C.A., Zhang, L., Cai, D. (2019). Endo-lysosomal pathway and ubiquitin-proteasome system dysfunction in Alzheimer's disease pathogenesis. Neuroscience Letters, 703, 68-78. [CrossRef]
  • 68. Zucca, F.A., Vanna, R., Cupaioli, F.A., Bellei, C., Palma, A.D., Silvestre, D.D., Mauri, P., Grassi, S., Prinetti, A., Casella, L., Sulzer, D., Zecca, L. (2018). Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson's disease. NPJ Parkinson’s Disease, 4, 17. [CrossRef]
  • 69. Pao, P.C., Patnaik, D., Watson, L.A., Gao, F., Pan, L., Wang, L., Adaikkan, C., Penney, J., Cam, H.P., Huang, W.C., Pantano, L., Lee, A., Nott, A., Phan, T. X., Gjoneska, E., Elmsaouri, S., Haggarty, S. J., Tsai, L.H. (2020). HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer's disease. Nature Communications, 11(1), 2484. [CrossRef]
  • 70. Tse, K.H., Herrup, K. (2017). DNA damage in the oligodendrocyte lineage and its role in brain aging. Mechanisms of Ageing and Development, 161(Pt A), 37-50. [CrossRef]
  • 71. Végh, M.J., Waard, M.C.D., Plujim, I.V.D., Ridwan, Y., Sassen, M.J.M., Nierop, P.V., Schors, R.C.V.D., Li, K.W., Hoeijlmakers, J.H.J., Smit, A.B., Kesteren, R.E.V. (2012). Synaptic proteome changes in a DNA repair deficient ercc1 mouse model of accelerated aging. Journal of Proteome Research, 11(3), 1855-67. [CrossRef]
  • 72. Fjell, A.M., Walhovd, K.B. (2010). Structural brain changes in aging: courses, causes and cognitive consequences. Reviews in the Neurosciences, 21(3), 187-221. [CrossRef]
  • 73. Isaev, N.K., Stelmashook, E.V., Genrikhs, E.E. (2019). Neurogenesis and brain aging. Reviews in the Neurosciences, 30(6), 573-580. [CrossRef]
  • 74. Ahlenius, H., Visan, V., Kokaia, M., Lindvall, O., Kokaia, Z. (2009). Neural stem and progenitor cells retain their potential for proliferation and differentiation into functional neurons despite lower number in aged brain. Journal of Neuroscience, 29(14), 4408-4419. [CrossRef]
  • 75. Cameron, H.A., Glover, L.R. (2015). Adult neurogenesis: beyond learning and memory. Annual Review of Psychology, 66, 53-81. [CrossRef]
  • 76. Enwere, E., Shingo, T., Gregg, C., Fujikawa, H., Ohta, S., Weiss, S. (2004). Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. The Journal of Neuroscience, 24(38), 8354-8365. [CrossRef]
  • 77. Drapeau, E., Mayo, W., Aurousseau, C., Le Moal, M., Piazza, P.V., Abrous, D.N. (2003). Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis. Proceedings of the National Academy of Sciences of the United States of America, 100(24), 14385-14390. [CrossRef]
  • 78. Jin, W.N., Shi, K., He, W., Sun, J.H., Van Kaer, L., Shi, F.D., Liu, Q. (2021). Neuroblast senescence in the aged brain augments natural killer cell cytotoxicity leading to impaired neurogenesis and cognition. Nature Neuroscience, 24(1), 61-73. [CrossRef]

MOLECULAR MECHANISMS IN BRAIN AGING

Year 2023, , 284 - 294, 20.01.2023
https://doi.org/10.33483/jfpau.1099963

Abstract

Objective: In this review, it is aimed to explain the molecular changes that occur with aging in the brain. The molecular mechanisms of brain aging are grouped under the headings of oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, autophagy, inflammation, disruption of lysosome and proteasome function, and impaired DNA repair and focused on these issues.
Result and Discussion: Aging is a multifactorial process, possibly resulting from accumulation of damage in organisms and/or decline in maintenance and repair mechanisms. With aging, many structural and functional changes occur in the brain. These changes create a predisposition to diseases such as Alzheimer's and Parkinson's along with neurodegenerative disorders. As the brain ages, its abilities such as learning, decision making and memory decrease. In order to develop therapeutic or protective approaches against brain aging-related diseases and functional disorders, there is a need to elucidate the molecular-level mechanisms of brain aging.

References

  • 1. Mattson, M.P., Arumugam T.V. (2018). Hallmarks of brain aging: adaptive and pathological modification by metabolic states. Cell Metabolism, 27(6), 1176–1199. [CrossRef]
  • 2. Alexander, G.E., Ryan, L., Bowers, D., Foster, T.C., Bizon, J.L., Geldmacher, D.S., Glisky, E.L. (2012). Characterizing cognitive aging in humans with links to animal models. Frontiers in Aging Neuroscience, 4, 21. [CrossRef]
  • 3. Dykiert, D., Der, G., Starr, J.M., Deary, I.J. (2012). Age differences in intra-individual variability in simple and choice reaction time: systematic review and meta-analysis. PLoS One, 7(10), e45759. [CrossRef]
  • 4. Levin, O., Fujiyama, H., Boisgontier, M.P., Swinnen, S.P., Summers, J.J. (2014). Aging and motor inhibition: a converging perspective provided by brain stimulation and imaging approaches. Neuroscience and Biobehavioral Reviews, 43, 100-117. [CrossRef]
  • 5. Aarsland, D., Creese, B., Politis, M., Chaudhuri, K.R., Ffytche, D.H., Weintraub, D., Ballard, C. (2017). Cognitive decline in parkinson disease. Nature Reviews Neurology, 13(4), 217-231. [CrossRef]
  • 6. Kalia, L. V., Lang, A. E. (2015). Parkinson's disease. Lancet, 386(9996), 896-912. [CrossRef]
  • 7. Mattson, M.P. (2004). Pathways towards and away from alzheimer's disease. Nature, 430(7000), 631-639. [CrossRef]
  • 8. Scheltens, P., Blennow, K., Breteler, M.M., de Strooper, B., Frisoni, G.B., Salloway, S., Van der Flier, W.M. (2016). Alzheimer's disease. Lancet, 388(10043), 505-517. [CrossRef]
  • 9. Isaev, N.K., Stelmashook, E.V., Stelmashook, N.N., Sharonova, I.N., Skrebitsky, V.G. (2013). Brain aging and mitochondria-targeted plastoquinone antioxidants of SkQ-type. Biochemistry (Mosc), 78(3), 295-300. [CrossRef]
  • 10. Isaev, N.K., Stelmashook, E.V., Genrikhs, E.E. (2019). Neurogenesis and brain aging. Rev Neurosci, 30(6), 573-580. [CrossRef]
  • 11. Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., Gargiulo, G., Testa, G., Cacciatore, F., Bonaduce, D., Abete, P. (2018). Oxidative stress, aging, and diseases. Clinical Interventions in Aging., 13, 757-72. [CrossRef]
  • 12. Ionescu-Tucker, A., Cotman, C.W. (2021). Emerging roles of oxidative stress in brain aging and alzheimer’s disease. Neurobiology of Aging., 107, 86-95. [CrossRef]
  • 13. Butterfield, D.A., Howard, B.J., LaFontaine, M.A. (2001). Brain oxidative stress in animal models of accelerated aging and the age-related neurodegenerative disorders, alzheimer’s disease and huntington’s disease. Current Medicinal Chemistry, 8(7), 815-28. [CrossRef]
  • 14. Zhang, Y., Ding, C., Cai, Y., Chen, X., Zhao, Y., Liu, X., Zhang, J., Sun, S., Liu, W. (2021). Astilbin ameliorates oxidative stress and apoptosis in D-galactose-induced senescence by regulating the PI3K/Akt/m-TOR signaling pathway in the brains of mice. International Immunopharmacology, 99, 108035. [CrossRef]
  • 15. Aydın, A.F., Çoban, J., Doğan-Ekici, I., Betül-Kalaz, E., Doğru-Abbasoğlu, S., Uysal, M.(2016). Carnosine and taurine treatments diminished brain oxidative stress and apoptosis in D-galactose aging model. Metabolic Brain Disease, 31(2), 337-45. [CrossRef]
  • 16. Singh, S., Singh, A.K., Garg, G., Rizvi, S.I.(2018). Fisetin as a caloric restriction mimetic protects rat brain against aging induced oxidative stress, apoptosis and neurodegeneration. Life Sciences, 193, 171-179. [CrossRef]
  • 17. Garg, G., Singh, S., Singh, A.K., Rizvi, S.I. (2018). N-acetyl-l-cysteine attenuates oxidative damage and neurodegeneration in rat brain during aging. Canadian Journal of Physiology and Pharmacology, 96(12), 1189-1196. [CrossRef]
  • 18. Wan, J.Z., Wang, R., Zhou, Z.Y., Deng, L.L., Zhang, C.C., Liu, C.Q., Zhao, H.X., Yuan, C.F., He, Y.M., Dun, Y.Y., Yuuan, D., Wang, T. (2020). Saponins of panax japonicus confer neuroprotection against brain aging through mitochondrial related oxidative stress and autophagy in rats. Current Pharmaceutical Biotechnology, 21(8), 667-680. [CrossRef]
  • 19. Yang, C., DeMars, K.M., Candelario-Jalil, E. (2018). Age-dependent decrease in adropin is associated with reduced levels of endothelial nitric oxide synthase and increased oxidative stress in the rat brain. Aging and Disease, 9(2), 322-330. [CrossRef]
  • 20. Alabarse, P.V.G., Hackenhaar, F.S., Medeiros, T.M., Mendes, M.F.A., Viacava, P.R., Schüller, A.K., Salomon, T.B., Ehrenbrink, G., Benfato, M.S. (2011). Oxidative stress in the brain of reproductive male rats during aging. Experimental Gerontology, 46(4), 241-8. [CrossRef]
  • 21. Li, X., Chen, Y., Shao, S., Tang, Q., Chen, W., Chen, Y., Xu, X. (2016). Oxidative stress induces the decline of brain EPO expression in aging rats. Experimental Gerontology, 83, 89-93. [CrossRef]
  • 22. Tatarkova , Z., Kovalska , M., Timkova, V., Racay,P., Lehotsky, J., Kaplan, P. (2016). The effect of aging on mitochondrial complex I and the extent of oxidative stress in the rat brain cortex. Neurochemical Research, 41(8), 2160-72. [CrossRef]
  • 23. Navarro, A., Boveris, A. (2010). Brain mitochondrial dysfunction in aging, neurodegeneration, and parkinson's disease. Frontiers in Aging Neuroscience, 2, 34. [CrossRef]
  • 24. Leuner, K., Hauptmann, S., Abdel-Kader, R., Scherping, I., Keil, U., Strosznajder, J.B., Eckert, A., Müller, W. E. (2007). Mitochondrial dysfunction: the first domino in brain aging and alzheimer's disease? Antioxid Redox Signal., 9(10), 1659-75. [CrossRef]
  • 25. Liu, H., Zhang, X., Xiao, J., Song, M., Cao, Y., Xiao, H., Liu, X. (2020). Astaxanthin attenuates d-galactose-induced brain aging in rats by ameliorating oxidative stress, mitochondrial dysfunction, and regulating metabolic markers. Food and Function, 11(5), 4103-4113. [CrossRef]
  • 26. Boveris, A., Navarro, A. (2008). Brain mitochondrial dysfunction in aging. IUBMB Life, 60(5), 308-14. [CrossRef]
  • 27. Li, Y., Yu, H., Chen, C., Li, S., Zhang, Z., Xu, H., Zhu, F., Liu, J., Spencer, P.S., Dai, Z., Yang, X. (2020). Proteomic profile of mouse brain aging contributions to mitochondrial dysfunction, DNA oxidative damage, loss of neurotrophic factor, and synaptic and ribosomal proteins. Oxidative Medicine Cellular Longevity, 5408452. [CrossRef]
  • 28. Gauba, E., Guo, L., Du, H. (2017). Cyclophilin D promotes brain mitochondrial F1FO ATP synthase dysfunction in aging mice. Journal of Alzheimer's Disease, 55(4), 1351-1362. [CrossRef]
  • 29. Klosinski, L.P., Yao, J., Yin, F., Fonteh, A.N., Harrington, M.G., Christensen, T.A., Trushina, E., Brinton, R.D. (2015). White matter lipids as a ketogenic fuel supply in aging female brain: implications for alzheimer's disease. EbioMedicine, 2(12), 1888-904. [CrossRef]
  • 30. Brown, M.K., Naidoo, N. (2012). The endoplasmic reticulum stress response in aging and age-related diseases. Frontiers in Physiology, 3, 263. [CrossRef]
  • 31. Anelli, T., Sitia, R. (2008). Protein quality control in the early secretory pathway.The EMBO Journal, 27(2), 315-27. [CrossRef]
  • 32. Oakes, S.A., Papa, F.R. (2015). The role of endoplasmic reticulum stress in human pathology. Annual Review of Pathology, 10, 173-94. [CrossRef]
  • 33. Wang, S., Kaufman, R. J. (2012). The impact of the unfolded protein response on human disease. The Journal of Cell Biology, 197(7), 857-67. [CrossRef]
  • 34. Bertolotti, A., Zhang, Y., Hendershot, L.M., Harding, H.P., Ron, D. (2000). Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nature Cell Biology, 2(6), 326-32. [CrossRef]
  • 35. Ma, K., Vattem, K.M., Wek, R.C. (2002). Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stress. The Journal of Biological Chemistry, 277(21), 18728-35. [CrossRef]
  • 36. Shen, J., Linda, X.C., Hendershot, L., Prywes, R. (2002). ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of golgi localization signals. Developmental Cell, 3(1), 99-111. [CrossRef]
  • 37. Oakes, S. A. (2020). Endoplasmic reticulum stress signaling in cancer cells. The American Journal of Pathology, 190(5), 934-946. [CrossRef]
  • 38. Taylor, R.C. (2016). Aging and the UPR(ER). Brain Research, 1648, 588-593. [CrossRef]
  • 39. Oh, J.H., Nam, T.J. (2019). Hydrophilic glycoproteins of an edible green alga capsosiphon fulvescens prevent aging-induced spatial memory impairment by suppressing GSK-3β-Mediated ER stress in dorsal hippocampus. Marine Drugs, 17(3), 168. [CrossRef]
  • 40. Naidoo, N, Ferber, M., Master, M., Zhu, Y., Pack, A.I. (2008). Aging impairs the unfolded protein response to sleep deprivation and leads to proapoptotic signaling. The Journal of Neuroscience, 28(26), 6539-48. [CrossRef]
  • 41. Naidoo, N., Zhu, J., Galante, R.J., Lian, J., Strus, E., Lee, A., Keenan, B.T., Pack, A.I. (2018). Reduction of the molecular chaperone binding immunoglobulin protein (BiP) accentuates the effect of aging on sleep-wake behavior. Neurobiology of Aging, 69, 10-25. [CrossRef]
  • 42. Hussain, S.G., Ramaiah, K.V. (2007). Reduced eIF2alpha phosphorylation and increased proapoptotic proteins in aging. Biochemical Biophysical Research Communications, 355, 365-370. [CrossRef]
  • 43. Plaza-Zabala, A., Sierra-Torre, V., Sierra, A. (2017). Autophagy and microglia: novel partners in neurodegeneration and aging. International Journal of Molecular Sciences, 18(3), 598. [CrossRef]
  • 44. Loeffler, D.A. (2019). Influence of normal aging on brain autophagy: a complex scenario. Frontiers in Aging Neuroscience, 11, 49. [CrossRef]
  • 45. Liu, A.D., Guo, E.S., Yang, J.K., Yang, Y., Liu, S.P., Jiang, X.J., Hu, Q., Dirsch, O., Dahmen, U., Zhang, C.T., Gewirtz, D.A., Fang, H.S. (2018). Young plasma reverses age-dependent alterations in hepatic function through the restoration of autophagy. Aging Cell, 17(1), e12708. [CrossRef]
  • 46. LaRocca, T.J., Henson, G.D., Thorburn, A., Sindler, A.L., Pierce, G.L., Seals, D.R. (2012). Translational evidence that impaired autophagy contributes to arterial ageing. Journal of Physiology-London, 590, 3305-3316. [CrossRef]
  • 47. LaRocca, T.J., Gioscia-Ryan, R.A., Hearon, C.M., Seals, D.R. (2013). The autophagy enhancer spermidine reverses arterial aging. Mechanisms of Ageing and Development, 134, 314-320. [CrossRef]
  • 48. Cao Y., Klionsky D.J. (2007). Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein. Cell Research, 17, 839–849. [CrossRef]
  • 49. Mizushima N., Yoshimori T., Levine B. (2010). Methods in mammalian autophagy research. Cell, 140, 313– 326. [CrossRef]
  • 50. Shen, K., Liu, X., Chen, D., Chang, J., Zhang, Y., Kou, X. (2021). Voluntary wheel-running exercise attenuates brain aging of rats through activating miR-130a-mediated autophagy. Brain Research Bulletin, 172, 203-211. [CrossRef]
  • 51. Cervellati, C., Trentini, A., Pecorelli, A., Valacchi, G. (2020). Inflammation in neurological disorders: the thin boundary between brain and periphery. Antioxidants Redox Signaling, 33(3), 191-210. [CrossRef]
  • 52. Aguzzi, A., Barres, B.A., Bennett, M.L.(2013). Microglia: scapegoat, saboteur, or something else? Science, 339(6116), 156-61. [CrossRef]
  • 53. Cribbs, D.H., Berchtold N.C., Perreau V., Coleman P.D., Rogers J., Tenner A.J., Cotman C.W. (2012). Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study. Journal of Neuroinflammation, 9, 179. [CrossRef]
  • 54. Norden, D.M., Godbout J.P. (2013). Review: microglia of the aged brain: primed to be activated and resistant to regulation. Neuropathology and Applied Neurobiology, 39, 19–34. [CrossRef]
  • 55. Mosher K.I., Wyss-Coray T. (2014). Microglial dysfunction in brain aging and Alzheimer’s disease. Biochemical Pharmacology, 88, 594–604. [CrossRef]
  • 56. Marschallinger, J., Iram, T., Zardeneta, M., Lee, S.E., Lehallier, B., Haney, M.S., Pluvinage, J. V., Mathur, V., Hahn, O., Morgens, D.W., Kim, J., Tevini, J., Felder, T.K., Wolinski, H., Bertozzi, C.R., Bassik, M.C., Aigner, L., Wyss-Coray, T. (2020). Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain. Nature Neuroscience, 23(2), 194-208. [CrossRef]
  • 57. Elahi, F.M., Harvey, D., Altendahl, M., Brathaban, N., Fernandes, N., Casaletto, K.B., Staffaroni, A.M., Maillard, P., Hinman, J.D., Miller, B.L., DeCarli, C., Kramer, J.H., Goetzl, E.J.(2021). Elevated complement mediator levels in endothelial-derived plasma exosomes implicate endothelial innate inflammation in diminished brain function of aging humans. Scientifik Reports, 11(1), 16198. [CrossRef]
  • 58. Corlier, F., Hafzalla, G., Faskowitz, J., Kuller, L.H., Becker, J.T., Lopez, O.L., Thompson, P.M., Braskie, M.N. (2018). Systemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk. Neuroimage, 172, 118-129. [CrossRef]
  • 59. Sala-Llonch, R., Idland, A.V., Borza, T., Watne, L.O., Wyller, T.B., Brækhus, A., Zetterberg, H., Blennow, K., Walhovd, K.B., Fjell, A.M. (2017). Inflammation, amyloid, and atrophy in the aging brain: relationships with longitudinal changes in cognition. Journal of Alzheimer’s Disease, 58(3), 829-840. [CrossRef]
  • 60. Lindbergh, C.A., Casaletto, K.B., Staffaroni, A.M., Elahi, F., Walters, S.M., You, M., Neuhaus, J., Rivera Contreras, W., Wang, P., Karydas, A., Brown, J., Wolf, A., Rosen, H., Cobigo, Y., Kramer, J.H. (2020). Systemic tumor necrosis factor-alpha trajectories relate to brain health in typically aging older adults. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 75, 1558-1565. [CrossRef]
  • 61. Spencer, S.J., D'Angelo, H., Soch, A., Watkins, L.R., Maier, S.F., Barrientos, R.M. (2017). High-fat diet and aging interact to produce neuroinflammation and impair hippocampal- and amygdalar-dependent memory. Neurobiology of Aging, 58, 88-101. [CrossRef]
  • 62. Keller, J.N., Dimayuga, E., Chen, Q., Thorpe, J., Gee, J., Ding, Q. (2004). Autophagy, proteasomes, lipofuscin, and oxidative stress in the aging brain. The International Journal of Biochemistry Cell Biology, 36(12), 2376-91 [CrossRef]
  • 63. Farout, L., Friguet, B. (2006). Proteasome function in aging and oxidative stress: implications in protein maintenance failure. Antioxidants Redox Signaling, 8(1-2), 205-16. [CrossRef]
  • 64. Kukan, M. (2004). Emerging roles of proteasomes in ischemia-reperfusion injury of organs. Journal of Physiology and Pharmacology, 55(1 Pt 1), 3-15. [CrossRef]
  • 65. Sun-Wang, J. L., Ivanova, S., Zorzano, A. (2020). The dialogue between the ubiquitin-proteasome system and autophagy: Implications in ageing. Ageing Research Reviews, 64, 101203. [CrossRef]
  • 66. Eldeeb, M. A. (2021). N-Terminal-Dependent protein degradation and targeting cancer cells. Anticancer Agents in Medicinal Chemistry, 21(2), 231-236. [CrossRef]
  • 67. Cao, J., Zhong, M.B., Taro, C.A., Zhang, L., Cai, D. (2019). Endo-lysosomal pathway and ubiquitin-proteasome system dysfunction in Alzheimer's disease pathogenesis. Neuroscience Letters, 703, 68-78. [CrossRef]
  • 68. Zucca, F.A., Vanna, R., Cupaioli, F.A., Bellei, C., Palma, A.D., Silvestre, D.D., Mauri, P., Grassi, S., Prinetti, A., Casella, L., Sulzer, D., Zecca, L. (2018). Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson's disease. NPJ Parkinson’s Disease, 4, 17. [CrossRef]
  • 69. Pao, P.C., Patnaik, D., Watson, L.A., Gao, F., Pan, L., Wang, L., Adaikkan, C., Penney, J., Cam, H.P., Huang, W.C., Pantano, L., Lee, A., Nott, A., Phan, T. X., Gjoneska, E., Elmsaouri, S., Haggarty, S. J., Tsai, L.H. (2020). HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer's disease. Nature Communications, 11(1), 2484. [CrossRef]
  • 70. Tse, K.H., Herrup, K. (2017). DNA damage in the oligodendrocyte lineage and its role in brain aging. Mechanisms of Ageing and Development, 161(Pt A), 37-50. [CrossRef]
  • 71. Végh, M.J., Waard, M.C.D., Plujim, I.V.D., Ridwan, Y., Sassen, M.J.M., Nierop, P.V., Schors, R.C.V.D., Li, K.W., Hoeijlmakers, J.H.J., Smit, A.B., Kesteren, R.E.V. (2012). Synaptic proteome changes in a DNA repair deficient ercc1 mouse model of accelerated aging. Journal of Proteome Research, 11(3), 1855-67. [CrossRef]
  • 72. Fjell, A.M., Walhovd, K.B. (2010). Structural brain changes in aging: courses, causes and cognitive consequences. Reviews in the Neurosciences, 21(3), 187-221. [CrossRef]
  • 73. Isaev, N.K., Stelmashook, E.V., Genrikhs, E.E. (2019). Neurogenesis and brain aging. Reviews in the Neurosciences, 30(6), 573-580. [CrossRef]
  • 74. Ahlenius, H., Visan, V., Kokaia, M., Lindvall, O., Kokaia, Z. (2009). Neural stem and progenitor cells retain their potential for proliferation and differentiation into functional neurons despite lower number in aged brain. Journal of Neuroscience, 29(14), 4408-4419. [CrossRef]
  • 75. Cameron, H.A., Glover, L.R. (2015). Adult neurogenesis: beyond learning and memory. Annual Review of Psychology, 66, 53-81. [CrossRef]
  • 76. Enwere, E., Shingo, T., Gregg, C., Fujikawa, H., Ohta, S., Weiss, S. (2004). Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. The Journal of Neuroscience, 24(38), 8354-8365. [CrossRef]
  • 77. Drapeau, E., Mayo, W., Aurousseau, C., Le Moal, M., Piazza, P.V., Abrous, D.N. (2003). Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis. Proceedings of the National Academy of Sciences of the United States of America, 100(24), 14385-14390. [CrossRef]
  • 78. Jin, W.N., Shi, K., He, W., Sun, J.H., Van Kaer, L., Shi, F.D., Liu, Q. (2021). Neuroblast senescence in the aged brain augments natural killer cell cytotoxicity leading to impaired neurogenesis and cognition. Nature Neuroscience, 24(1), 61-73. [CrossRef]
There are 78 citations in total.

Details

Primary Language Turkish
Subjects Pharmacology and Pharmaceutical Sciences
Journal Section Collection
Authors

Esra Özdek 0000-0003-0393-3335

Sevtap Han 0000-0001-6392-097X

Publication Date January 20, 2023
Submission Date April 7, 2022
Acceptance Date October 19, 2022
Published in Issue Year 2023

Cite

APA Özdek, E., & Han, S. (2023). BEYİN YAŞLANMASINDA MOLEKÜLER MEKANİZMALAR. Journal of Faculty of Pharmacy of Ankara University, 47(1), 284-294. https://doi.org/10.33483/jfpau.1099963
AMA Özdek E, Han S. BEYİN YAŞLANMASINDA MOLEKÜLER MEKANİZMALAR. Ankara Ecz. Fak. Derg. January 2023;47(1):284-294. doi:10.33483/jfpau.1099963
Chicago Özdek, Esra, and Sevtap Han. “BEYİN YAŞLANMASINDA MOLEKÜLER MEKANİZMALAR”. Journal of Faculty of Pharmacy of Ankara University 47, no. 1 (January 2023): 284-94. https://doi.org/10.33483/jfpau.1099963.
EndNote Özdek E, Han S (January 1, 2023) BEYİN YAŞLANMASINDA MOLEKÜLER MEKANİZMALAR. Journal of Faculty of Pharmacy of Ankara University 47 1 284–294.
IEEE E. Özdek and S. Han, “BEYİN YAŞLANMASINDA MOLEKÜLER MEKANİZMALAR”, Ankara Ecz. Fak. Derg., vol. 47, no. 1, pp. 284–294, 2023, doi: 10.33483/jfpau.1099963.
ISNAD Özdek, Esra - Han, Sevtap. “BEYİN YAŞLANMASINDA MOLEKÜLER MEKANİZMALAR”. Journal of Faculty of Pharmacy of Ankara University 47/1 (January 2023), 284-294. https://doi.org/10.33483/jfpau.1099963.
JAMA Özdek E, Han S. BEYİN YAŞLANMASINDA MOLEKÜLER MEKANİZMALAR. Ankara Ecz. Fak. Derg. 2023;47:284–294.
MLA Özdek, Esra and Sevtap Han. “BEYİN YAŞLANMASINDA MOLEKÜLER MEKANİZMALAR”. Journal of Faculty of Pharmacy of Ankara University, vol. 47, no. 1, 2023, pp. 284-9, doi:10.33483/jfpau.1099963.
Vancouver Özdek E, Han S. BEYİN YAŞLANMASINDA MOLEKÜLER MEKANİZMALAR. Ankara Ecz. Fak. Derg. 2023;47(1):284-9.

Kapsam ve Amaç

Ankara Üniversitesi Eczacılık Fakültesi Dergisi, açık erişim, hakemli bir dergi olup Türkçe veya İngilizce olarak farmasötik bilimler alanındaki önemli gelişmeleri içeren orijinal araştırmalar, derlemeler ve kısa bildiriler için uluslararası bir yayım ortamıdır. Bilimsel toplantılarda sunulan bildiriler supleman özel sayısı olarak dergide yayımlanabilir. Ayrıca, tüm farmasötik alandaki gelecek ve önceki ulusal ve uluslararası bilimsel toplantılar ile sosyal aktiviteleri içerir.