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İnsanlarda yaşlanmanın beyin üzerindeki etkisi: Kapsamlı bir inceleme

Yıl 2025, Cilt: 2 Sayı: 3, 8 - 21, 20.03.2025
https://doi.org/10.5281/zenodo.15055863

Öz

Özet
İnsan beyni yaklaşık olarak üç kiloluk bir organdır ve duyusal, motor ve otonom sinir sistemleri aracılığıyla insan vücudunun en üst düzey komuta merkezi olarak hizmet etmektedir. Yaşlanma birçok moleküler ve metabolik olayın içerisinde bulunduğu kompleks bir süreçtir. Bu süreci açıklamaya çalışan birçok teori bulunmaktadır. Bu teoriler tek başına düşünülemez ve birbiriyle bağlantılıdır. Yaşlanma sürecinde, birçok organda fonksiyonel gerileme meydana gelmektedir. Bu süreçte beyinde histolojik, fizyolojik ve moleküler düzeyde değişime maruz kalmaktadır. Yaşlanmayla birlikte görülen başlıca morfolojik değişiklikler arasında beyin hacmi kaybı, gri ve beyaz madde atrofisi, kortikal incelme, girifikasyon kaybı ve ventriküler genişleme yer almaktadır. Yaşlanmayla beyinde meydana gelen hücresel, morfolojik ve fonksiyonel değişikliklere özellikle nöron ve glia hücrelerinde gerçekleşen moleküler değişimlerin neden olduğu bildirilmiştir. Beyin yaşlanmasının, büyük bir halk sağlığı sorunu olduğu bilinen Alzheimer ve Parkinson hastalıkları da dahil olmak üzere çeşitli nörodejeneratif hastalıklar için en büyük risk faktörü olduğu bilinmektedir. Bu nedenle beynin yaşlanma mekanizmasının anlaşılması önemlidir. Bu derlemede yaşlanma sürecinde beyinde meydana gelen histolojik, fizyolojik ve moleküler değişiklikler üzerine odaklanmaktadır.
Anahtar kelime: Yaşlanma, Beyin, Alzheimer hastalığı, Parkinson hastalığı

Kaynakça

  • Referans1 Hou Y, Dan X, Babbar M, et al. Ageing as a risk factor for neurodegenerative disease. Nature reviews. Neurology, 2019; 15(10): 565–581.
  • Referans2 Youssef SA, Capucchio MT, Rofina JE, et al. Pathology of the aging brain in domestic and laboratory animals, and animal models of human neurodegenerative diseases. Vet Pathol. 2016; 53(2): 327-48.
  • Referans3 Lull ME, Block ML. Microglial activation and chronic neurodegeneration. Neurotherapeutics. 2010; 7(4): 354-65.
  • Referans4 Blinkouskaya Y, Caçoilo A, Gollamudi T, et al. Brain aging mechanisms with mechanical manifestations. Mech Ageing Dev. 2021; 200: 111575.
  • Referans5 Medvedev ZA. An attempt at a rational classification of theories of ageing. Biol Rev Camb Philos Soc. 1990; 65(3): 375-98.
  • Referans6 Tosato M, Zamboni V, Ferrini A, Cesari M. The aging process and potential interventions to extend life expectancy. Clin Interv Aging. 2007; 2(3): 401-12.
  • Referans7 Weinert BT, Timiras PS. Invited review: Theories of aging. J Appl Physiol. 2003; 95(4): 1706-16.
  • Referans8 Sastre J, Pallardó FV, García de la Asunción J, Viña J. Mitochondria, oxidative stress and aging. Free Radic Res. 2000; 32(3): 189-98.
  • Referans9 Bratic A, Larsson NG. The role of mitochondria in aging. J Clin Invest. 2013; 123(3): 951-7.
  • Referans10 Barja G. Free radicals and aging. Trends in Neurosciences. 2004; 27(10): 595-600.
  • Referans11 Xia S, Zhang X, Zheng S, et al. An update on inflamm-aging: mechanisms, prevention, and treatment. Journal of Immunology Research. 2016; 2016(1): 1-12.
  • Referans12 Chung HY, Kim HJ, Kim JW, et al. The inflammation hypothesis of aging – Molecular modulation by calorie restriction. Ann N Y Acad Sci. 2001; 928: 327–35.
  • Referans13 Khansari N, Shakiba Y, Mahmoudi M. Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer. Recent Pat Inflamm Allergy Drug Discov. 2009; 3(1): 73-80.
  • Referans14 Franceschi C, Bonafe M, Valensin S, et al. Inflamm-aging–An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000; 908: 244–54.
  • Referans15 Epelbaum J, Terrien J. Mini-review: Aging of the neuroendocrine system: Insights from nonhuman primate models. Prog Neuropsychopharmacol Biol Psychiatry. 2020; 100:109854.
  • Referans16 Gupta D, Morley JE. Hypothalamic-pituitary-adrenal (HPA) axis and aging. Compr Physiol. 2014; 4(4): 1495-510.
  • Referans17 Mohan A, Mather KA, Thalamuthu A et al. Gene expression in the aging human brain: an overview. Curr Opin Psychiatry. 2016; 29(2): 159-67.
  • Referans18 López-Otín C, Blasco MA, Partridge L, et al. The hallmarks of aging. Cell. 2013; 153(6): 1194-217.
  • Referans19 Klump BM, Schmidt JC. Advances in understanding telomerase assembly. Biochem Soc Trans. 2023; 51(6): 2093-2101.
  • Referans20 Artandi SE. Telomeres, telomerase, and human disease. N Engl J Med. 2006; 355(12): 1195-7.
  • Referans21 Shay JW, Wright WE. Telomerase activity in human cancer. Curr Opin Oncol. 1996; 8(1): 66-71.
  • Referans22 Jaskelioff M, Muller FL, Paik JH, et al. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature. 2011; 469(7328): 102-6.
  • Referans23 Bernardes de Jesus B, Vera E, Schneeberger K, et al. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol Med. 2012; 4(8): 691-704.
  • Referans24 Zhang P, Dilley C, Mattson MP. DNA damage responses in neural cells: Focus on the telomere. Neuroscience. 2007; 145(4): 1439-48.
  • Referans 25 Lee J, Jo YS, Sung YH et al. Telomerase Deficiency Affects Normal Brain Functions in Mice. Neurochem Res. 2010; 35: 211–218.
  • Referans26 Zhang J, Kong Q, Zhang Z, et al. Telomere dysfunction of lymphocytes in patients with Alzheimer disease. Cogn Behav Neurol. 2003; 16(3): 170-6.
  • Referans27 Honig LS, Schupf N, Lee JH, et al. Shorter telomeres are associated with mortality in those with APOE epsilon4 and dementia. Ann Neurol. 2006; 60(2): 181-187.
  • Referans28 Blinkouskaya Y, Weickenmeier J. Brain shape changes associated with cerebral atrophy in healthy aging and Alzheimer’s disease. Front Mech Eng. 2021; 7: 705653.
  • Referans29 Dekaban AS. Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights. Ann Neurol. 1978; 4(4): 345-56.
  • Referans30 Ho KC, Roessmann U, Straumfjord JV, Monroe G. Analysis of brain weight. I. Adult brain weight in relation to sex, race, and age. Arch Pathol Lab Med. 1980; 104(12): 635-639.
  • Referans31 Svennerholm L, Boström K, Jungbjer B. Changes in weight and compositions of major membrane components of human brain during the span of adult human life of Swedes. Acta Neuropathol. 1997; 94(4): 345-52.
  • Referans32 Teissier T, Boulanger E, Deramecourt V. Normal ageing of the brain: Histological and biological aspects. Rev Neurol. 2020; 176(9): 649– 660.
  • Referans33 Hedman AM, van Haren NEM, Schnack HG, et al. Human brain changes across the life span: a review of 56 longitudinal magnetic resonance imaging studies. Hum Brain Mapp. 2012; 33(8): 1987–2002.
  • Referans34 Resnick SM, Pham DL, Kraut MA, et al. Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J Neurosci. 2003; 23(8): 3295–3301.
  • Referans35 Brody H. Organization of the cerebral cortex. III. A study of aging in the human cerebral cortex. J Comp Neurol. 1955; 102(2): 511–556.
  • Referans36 Haug H, Kühl S, Mecke E, et al. The significance of morphometric procedures in the investigation of age changes in cytoarchitectonic structures of human brain. J Hirnforsch. 1984; 25(4): 353–374.
  • Referans37 Gómez-Isla T, Hollister R, West H, et al. Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer’s disease. Ann Neurol. 1997; 41(1): 17–24. 38.Peters A. The absence of significant neuronal loss from cerebral cortex with age. Neurobiol Aging. 1993; 14(6): 657–658. Referans39 West MJ, Coleman PD, Flood DG, Troncoso JC. Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer’s disease. Lancet 1994; 344(8925): 769–772.
  • Referans40 Dickstein DL, Kabaso D, Rocher AB, et al. Changes in the structural complexity of the aged brain. Aging Cell. 2007; 6(3): 275–284.
  • Referans41 Good CD, Johnsrude IS, Ashburner J, et al. A voxel-based morphometric study of ageing in 465 normal adult human brains. NeuroImage. 2001; 14(1 Pt 1):21-36.
  • Referans42 Taki Y, Kinomura S, Sato K, et al. A longitudinal study of gray matter volume decline with age and modifying factors. Neurobiol Aging. 2011; 32(5): 907–915.
  • Referans43 Fjell AM, Westlye LT, Grydeland H, et al. Accelerating cortical thinning: unique to dementia or universal in aging? Cereb Cortex. 2014; 24(4): 919–934.
  • Referans44 Lamballais S, Vinke EJ, Vernooij MW, et al. Cortical gyrification in relation to age and cognition in older adults. NeuroImage. 2020; 212: 116637.
  • Referans45 Lemaitre H, Goldman AL, Sambataro F, et al. Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume? Neurobiol Aging. 2012; 33(3): 617.e1–617.e9.
  • Referans46 Madan CR. Age-related decrements in cortical gyrification: Evidence from an accelerated longitudinal dataset. Eur J Neurosci. 2021; 53(5):1661-1671.
  • Referans47 Storsve AB, Fjell AM, Tamnes CK, et al. Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change. J Neurosci. 2014; 34(25): 8488-8498.
  • Referans48 Fjell AM, Walhovd KB. Structural brain changes in aging: courses, causes and cognitive consequences. Rev Neuroscis. 2010; 21(3): 187–221.
  • Referans49 Liu H, Yang Y, Xia Y, et al. Aging of cerebral white matter. Ageing Res Rev. 2017; 34, 64–76.
  • Referans50 Driscoll I, Davatzikos C, An Y, et al. Longitudinal pattern of regional brain volüme change differentiates normal aging from MCI. Neurology. 2009; 72(22): 1906–1913.
  • Referans51.Salat DH, Tuch DS, Greve DN, et al. Age-related alterations in white matter microstructure measured by diffusion tensor imaging. Neurobiol Aging. 2005; 26(8): 1215–1227.
  • Referans52 Bennett IJ, Madden DJ. Disconnected aging: cerebral white matter integrity and age-related differences in cognition. Neuroscience. 2014; 276: 187–205.
  • Referans53 Peters A, Verderosa A, Sethares C. The neuroglial population in the primary visual cortex of the aging rhesus monkey. Glia. 2008; 56(11): 1151–1161.
  • Referans54 Peters A. The effects of normal aging on myelinated nerve fibers in monkey central nervous system. Front Neuroanat. 2009; 3: 11.
  • Referans55 Shook BA, Lennington JB, Acabchuk RL, et al. Ventriculomegaly associated with ependymal gliosis and declines in barrier integrity in the aging human and mouse brain. Aging Cell. 2014; 13: 340–350.
  • Referans56 Pfefferbaum A, Mathalon DH, Sullivan EV, et al. A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Arch Neurol. 1994; 51(9): 874–887.
  • Referans57 Resnick SM, Goldszal AF, Davatzikos C, et al. One-year age changes in MRI brain volumes in older adults. Cereb Cortex. 2000; 10(5): 464-72.
  • Referans58 Riddle DR, Sonntag WE, Lichtenwalner RJ. Microvascular plasticity in aging. Ageing Res Rev. 2003; 2(2): 149–168.
  • Referans59 Brown WR, Thore CR. Review: cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol Appl Neurobiol. 2011; 37(1): 56-74.
  • Referans60 Isaev NK, Stelmashook EV, Genrikhs EE. Neurogenesis and brain aging. Rev Neurosci. 2019; 30(6): 573-580.
  • Referans61 Galvan V, Jin K. Neurogenesis in the aging brain. Clin Interv Aging. 2007; 2(4): 605-10.
  • Referans62 Ahlenius H, Visan V, Kokaia M, et al. Neural stem and progenitor cells retain their potential for proliferation and differentiation into functional neurons despite lower number in aged brain. J Neurosci. 2009; 29(14): 4408-19.
  • Referans63 Enwere E, Shingo T, Gregg C, et al. Aging Results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci. 2004; 24: 8354–8365.
  • Referans64 Zhang H, Li J, Ren J, et al. Single-nucleus transcriptomic landscape of primate hippocampal aging. Protein Cell. 2021; 12(9): 695–716.
  • Referans65 Mahncke HW, Bronstone A, Merzenich MM. Brain plasticity and functional losses in the aged: scientific bases for a novel intervention. Prog Brain Res. 2006; 157: 81-109.
  • Referans66 Caserta MT, Bannon Y, Fernandez F, et al. Normal brain aging clinical, immunological, neuropsychological, and neuroimaging features. Int Rev Neurobiol. 2009; 84: 1-19.
  • Referans67 Lee P, Kim J, Williams R, et al. Effects of aging on blood brain barrier and matrix metalloproteases following controlled cortical impact in mice. Exp Neurol. 2012; 234(1): 50-61.
  • Referans68 Elahy M, Jackaman C, Mamo JC, et al. Blood-brain barrier dysfunction developed during normal aging is associated with inflammation and loss of tight junctions but not with leukocyte recruitment. Immun Ageing. 2015;12: 2.
  • Referans69 Henry CJ, Huang Y, Wynne AM, Godbout JP. Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1beta and anti-inflammatory IL-10 cytokines. Brain Behav Immun. 2009; 23(3): 309-17.
  • Referans70 Perry VH, Matyszak MK, Fearn S. Altered antigen expression of microglia in the aged rodent CNS. Glia. 1993; 7(1): 60-7.
  • Referans71 Stichel CC, Luebbert H. Inflammatory processes in the aging mouse brain: participation of dendritic cells and T-cells. Neurobiol Aging. 2007; 28(10): 1507-21.
  • Referans72 Letiembre M, Hao W, Liu Y, et al. Innate immune receptor expression in normal brain aging. Neuroscience. 2007; 146(1): 248-54.
  • Referans73 Griffin R, Nally R, Nolan Y, et al. The age-related attenuation in long-term potentiation is associated with microglial activation. J Neurochem. 2006; 99(4): 1263-72.
  • Referans74 Griciuc A, Serrano-Pozo A, Parrado AR, et al. Alzheimer's disease risk gene CD33 inhibits microglial uptake of amyloid beta. Neuron. 2013; 78(4): 631-43.
  • Referans75 Li L, Xiong WC, Mei L. Neuromuscular junction formation, aging, and disorders. Annu Rev Physiol. 2018; 80: 159-188.
  • Referans76 Peters A. Structural changes that occur during normal aging of primate cerebral hemispheres. Neurosci Biobehav Rev. 2002; 26(7): 733-41.
  • Referans77 Panagiotou M, Michel S, Meijer JH, Deboer T. The aging brain: sleep, the circadian clock and exercise. Biochem Pharmacol. 2021; 191: 114563.
  • Referans78 Satoh A, Imai SI, Guarente L. The brain, sirtuins, and ageing. Nat Rev Neurosci. 2017; 18(6): 362-374.
  • Referans79 Hinman JD, Abraham CR. What's behind the decline? The role of white matter in brain aging. Neurochem Res. 2007; 32(12): 2023-31.
  • Referans80 Sloane JA, Hinman JD, Lubonia M, et al. Age-dependent myelin degeneration and proteolysis of oligodendrocyte proteins is associated with the activation of calpain-1 in the rhesus monkey. J Neurochem. 2003; 84(1): 157-68.
  • Referans81 Hinman JD, Peters A, Cabral H, et al. Age-related molecular reorganization at the node of Ranvier. J Comp Neurol. 2006; 495(4): 351-62.
  • Referans82 Ravera S, Bartolucci M, Cuccarolo P, et al. Oxidative stress in myelin sheath: The other face of the extramitochondrial oxidative phosphorylation ability. Free Radic Res. 2015; 49(9): 1156-64.
  • Referans83 Mavroudis IA, Manani MG, Petrides F, et al. Age-related dendritic and spinal alterations of pyramidal cells of the human visual cortex. Folia Neuropathol. 2015; 53(2): 100-10.
  • Referans84 Liu RH, Bertolotto C, Engelhardt JK, Chase MH. Age-related changes in soma size of neurons in the spinal cord motor column of the cat. Neurosci Lett. 1996; 211(3): 163-6.
  • Referans85 Stahon KE, Bastian C, Griffith S, et al. Age-Related Changes in Axonal and Mitochondrial Ultrastructure and Function in White Matter. J Neurosci. 2016; 36(39): 9990-10001.
  • Referans86 Fan Z, Bin L. Will Sirtuin 2 Be a Promising Target for Neuroinflammatory Disorders? Front. Cell. Neurosci. 2022; 16:915587.
  • Referans87 Herskovits AZ, Guarente L. SIRT1 in neurodevelopment and brain senescence. Neuron. 2014; 81(3): 471-83.
  • Referans88 Gao J, Wang WY, Mao YW, et al. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature. 2010; 466(7310): 1105-9.
  • Referans89 Michán S, Li Y, Chou MM, et al. SIRT1 is essential for normal cognitive function and synaptic plasticity. J Neurosci. 2010; 30(29): 9695-707.
  • Referans90 Jiang M, Wang J, Fu J, et al. Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets. Nat Med. 2011; 18(1): 153-8.
  • Referans91 Jeong H, Cohen DE, Cui L, et al. Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway. Nat Med. 2011; 18(1): 159-65.
  • Referans92 Puigoriol-Illamola D, Martínez-Damas M, Griñán-Ferré C, Pallàs M. Chronic Mild stress modified epigenetic mechanisms leading to accelerated senescence and impaired cognitive performance in mice. Int J Mol Sci. 2020; 21(3): 1154.
  • Referans93 Lu W, Wang Q, Xu C, et al. SUMOylation is essential for Sirt2 tumor-suppressor function in neuroblastoma. Neoplasia. 2021; 23(1):129-139.
  • Referans94 Diaz-Perdigon T, Belloch FB, Ricobaraza A, et al. Early sirtuin 2 inhibition prevents age-related cognitive decline in a senescence-accelerated mouse model. Neuropsychopharmacology. 2020; 45(2): 347-357.
  • Referans95 Outeiro TF, Kontopoulos E, Altmann SM, et al. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science. 2007; 317(5837): 516-9.
  • Referans96 Ramadori G, Coppari R. Does hypothalamic SIRT1 regulate aging?. Aging (Albany NY). 2011; 3: 325-328.
  • Referans97 Cho SH, Chen JA, Sayed F, et al. SIRT1 deficiency in microglia contributes to cognitive decline in aging and neurodegeneration via epigenetic regulation of IL-1β. J Neurosci. 2015; 35(2): 807-18.
  • Referans98 Pais TF, Szegő ÉM, Marques O, et al. The NAD-dependent deacetylase sirtuin 2 is a suppressor of microglial activation and brain inflammation. EMBO J. 2013; 32(19): 2603-16.
  • Referans99 Dai SH, Chen T, Wang YH, et al. Sirt3 protects cortical neurons against oxidative stress via regulating mitochondrial Ca2+ and mitochondrial biogenesis. Int J Mol Sci. 2014; 15(8): 14591-609.
  • Referans100 Someya S, Yu W, Hallows WC, et al. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell. 2010; 143(5): 802-12.
  • Referans101 Satoh A, Imai S. Systemic regulation of mammalian ageing and longevity by brain sirtuins. Nat Commun. 2014; 5: 4211.
  • Referans102 Aging Biomarker Consortium, Bao H, Cao J, et al. Biomarkers of aging. Sci China Life Sci. 2023; 66: 893-1066.

The impact of aging on the brain in humans: A comprehensive review

Yıl 2025, Cilt: 2 Sayı: 3, 8 - 21, 20.03.2025
https://doi.org/10.5281/zenodo.15055863

Öz

Abstract
The human brain is an approximately three-pound organ and serves as the ultimate command center of the human body through the sensory, motor and autonomic nervous systems. Aging is a complex process involving many molecular and metabolic events. There are many theories that try to explain this process. These theories cannot be considered in isolation and are interconnected. During the aging process, functional decline occurs in many organs. In this process, the brain is subjected to changes at histological, physiological and molecular levels. The main morphological changes seen with aging include brain volume loss, gray and white matter atrophy, cortical thinning, loss of gyrification and ventricular enlargement. The cellular, morphological and functional changes that occur in the brain with aging have been reported to be caused by molecular changes, especially in neurons and glia cells. Brain aging is known to be the greatest risk factor for various neurodegenerative diseases, including Alzheimer's and Parkinson's diseases, which are known to be a major public health problem. Therefore, it is important to understand the mechanism of brain aging. This review focuses on the histological, physiological, and molecular changes that occur in the brain during the aging process.
Key words: Aging, Brain, Alzheimer's disease, Parkinson's disease

Kaynakça

  • Referans1 Hou Y, Dan X, Babbar M, et al. Ageing as a risk factor for neurodegenerative disease. Nature reviews. Neurology, 2019; 15(10): 565–581.
  • Referans2 Youssef SA, Capucchio MT, Rofina JE, et al. Pathology of the aging brain in domestic and laboratory animals, and animal models of human neurodegenerative diseases. Vet Pathol. 2016; 53(2): 327-48.
  • Referans3 Lull ME, Block ML. Microglial activation and chronic neurodegeneration. Neurotherapeutics. 2010; 7(4): 354-65.
  • Referans4 Blinkouskaya Y, Caçoilo A, Gollamudi T, et al. Brain aging mechanisms with mechanical manifestations. Mech Ageing Dev. 2021; 200: 111575.
  • Referans5 Medvedev ZA. An attempt at a rational classification of theories of ageing. Biol Rev Camb Philos Soc. 1990; 65(3): 375-98.
  • Referans6 Tosato M, Zamboni V, Ferrini A, Cesari M. The aging process and potential interventions to extend life expectancy. Clin Interv Aging. 2007; 2(3): 401-12.
  • Referans7 Weinert BT, Timiras PS. Invited review: Theories of aging. J Appl Physiol. 2003; 95(4): 1706-16.
  • Referans8 Sastre J, Pallardó FV, García de la Asunción J, Viña J. Mitochondria, oxidative stress and aging. Free Radic Res. 2000; 32(3): 189-98.
  • Referans9 Bratic A, Larsson NG. The role of mitochondria in aging. J Clin Invest. 2013; 123(3): 951-7.
  • Referans10 Barja G. Free radicals and aging. Trends in Neurosciences. 2004; 27(10): 595-600.
  • Referans11 Xia S, Zhang X, Zheng S, et al. An update on inflamm-aging: mechanisms, prevention, and treatment. Journal of Immunology Research. 2016; 2016(1): 1-12.
  • Referans12 Chung HY, Kim HJ, Kim JW, et al. The inflammation hypothesis of aging – Molecular modulation by calorie restriction. Ann N Y Acad Sci. 2001; 928: 327–35.
  • Referans13 Khansari N, Shakiba Y, Mahmoudi M. Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer. Recent Pat Inflamm Allergy Drug Discov. 2009; 3(1): 73-80.
  • Referans14 Franceschi C, Bonafe M, Valensin S, et al. Inflamm-aging–An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000; 908: 244–54.
  • Referans15 Epelbaum J, Terrien J. Mini-review: Aging of the neuroendocrine system: Insights from nonhuman primate models. Prog Neuropsychopharmacol Biol Psychiatry. 2020; 100:109854.
  • Referans16 Gupta D, Morley JE. Hypothalamic-pituitary-adrenal (HPA) axis and aging. Compr Physiol. 2014; 4(4): 1495-510.
  • Referans17 Mohan A, Mather KA, Thalamuthu A et al. Gene expression in the aging human brain: an overview. Curr Opin Psychiatry. 2016; 29(2): 159-67.
  • Referans18 López-Otín C, Blasco MA, Partridge L, et al. The hallmarks of aging. Cell. 2013; 153(6): 1194-217.
  • Referans19 Klump BM, Schmidt JC. Advances in understanding telomerase assembly. Biochem Soc Trans. 2023; 51(6): 2093-2101.
  • Referans20 Artandi SE. Telomeres, telomerase, and human disease. N Engl J Med. 2006; 355(12): 1195-7.
  • Referans21 Shay JW, Wright WE. Telomerase activity in human cancer. Curr Opin Oncol. 1996; 8(1): 66-71.
  • Referans22 Jaskelioff M, Muller FL, Paik JH, et al. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature. 2011; 469(7328): 102-6.
  • Referans23 Bernardes de Jesus B, Vera E, Schneeberger K, et al. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol Med. 2012; 4(8): 691-704.
  • Referans24 Zhang P, Dilley C, Mattson MP. DNA damage responses in neural cells: Focus on the telomere. Neuroscience. 2007; 145(4): 1439-48.
  • Referans 25 Lee J, Jo YS, Sung YH et al. Telomerase Deficiency Affects Normal Brain Functions in Mice. Neurochem Res. 2010; 35: 211–218.
  • Referans26 Zhang J, Kong Q, Zhang Z, et al. Telomere dysfunction of lymphocytes in patients with Alzheimer disease. Cogn Behav Neurol. 2003; 16(3): 170-6.
  • Referans27 Honig LS, Schupf N, Lee JH, et al. Shorter telomeres are associated with mortality in those with APOE epsilon4 and dementia. Ann Neurol. 2006; 60(2): 181-187.
  • Referans28 Blinkouskaya Y, Weickenmeier J. Brain shape changes associated with cerebral atrophy in healthy aging and Alzheimer’s disease. Front Mech Eng. 2021; 7: 705653.
  • Referans29 Dekaban AS. Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights. Ann Neurol. 1978; 4(4): 345-56.
  • Referans30 Ho KC, Roessmann U, Straumfjord JV, Monroe G. Analysis of brain weight. I. Adult brain weight in relation to sex, race, and age. Arch Pathol Lab Med. 1980; 104(12): 635-639.
  • Referans31 Svennerholm L, Boström K, Jungbjer B. Changes in weight and compositions of major membrane components of human brain during the span of adult human life of Swedes. Acta Neuropathol. 1997; 94(4): 345-52.
  • Referans32 Teissier T, Boulanger E, Deramecourt V. Normal ageing of the brain: Histological and biological aspects. Rev Neurol. 2020; 176(9): 649– 660.
  • Referans33 Hedman AM, van Haren NEM, Schnack HG, et al. Human brain changes across the life span: a review of 56 longitudinal magnetic resonance imaging studies. Hum Brain Mapp. 2012; 33(8): 1987–2002.
  • Referans34 Resnick SM, Pham DL, Kraut MA, et al. Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J Neurosci. 2003; 23(8): 3295–3301.
  • Referans35 Brody H. Organization of the cerebral cortex. III. A study of aging in the human cerebral cortex. J Comp Neurol. 1955; 102(2): 511–556.
  • Referans36 Haug H, Kühl S, Mecke E, et al. The significance of morphometric procedures in the investigation of age changes in cytoarchitectonic structures of human brain. J Hirnforsch. 1984; 25(4): 353–374.
  • Referans37 Gómez-Isla T, Hollister R, West H, et al. Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer’s disease. Ann Neurol. 1997; 41(1): 17–24. 38.Peters A. The absence of significant neuronal loss from cerebral cortex with age. Neurobiol Aging. 1993; 14(6): 657–658. Referans39 West MJ, Coleman PD, Flood DG, Troncoso JC. Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer’s disease. Lancet 1994; 344(8925): 769–772.
  • Referans40 Dickstein DL, Kabaso D, Rocher AB, et al. Changes in the structural complexity of the aged brain. Aging Cell. 2007; 6(3): 275–284.
  • Referans41 Good CD, Johnsrude IS, Ashburner J, et al. A voxel-based morphometric study of ageing in 465 normal adult human brains. NeuroImage. 2001; 14(1 Pt 1):21-36.
  • Referans42 Taki Y, Kinomura S, Sato K, et al. A longitudinal study of gray matter volume decline with age and modifying factors. Neurobiol Aging. 2011; 32(5): 907–915.
  • Referans43 Fjell AM, Westlye LT, Grydeland H, et al. Accelerating cortical thinning: unique to dementia or universal in aging? Cereb Cortex. 2014; 24(4): 919–934.
  • Referans44 Lamballais S, Vinke EJ, Vernooij MW, et al. Cortical gyrification in relation to age and cognition in older adults. NeuroImage. 2020; 212: 116637.
  • Referans45 Lemaitre H, Goldman AL, Sambataro F, et al. Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume? Neurobiol Aging. 2012; 33(3): 617.e1–617.e9.
  • Referans46 Madan CR. Age-related decrements in cortical gyrification: Evidence from an accelerated longitudinal dataset. Eur J Neurosci. 2021; 53(5):1661-1671.
  • Referans47 Storsve AB, Fjell AM, Tamnes CK, et al. Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change. J Neurosci. 2014; 34(25): 8488-8498.
  • Referans48 Fjell AM, Walhovd KB. Structural brain changes in aging: courses, causes and cognitive consequences. Rev Neuroscis. 2010; 21(3): 187–221.
  • Referans49 Liu H, Yang Y, Xia Y, et al. Aging of cerebral white matter. Ageing Res Rev. 2017; 34, 64–76.
  • Referans50 Driscoll I, Davatzikos C, An Y, et al. Longitudinal pattern of regional brain volüme change differentiates normal aging from MCI. Neurology. 2009; 72(22): 1906–1913.
  • Referans51.Salat DH, Tuch DS, Greve DN, et al. Age-related alterations in white matter microstructure measured by diffusion tensor imaging. Neurobiol Aging. 2005; 26(8): 1215–1227.
  • Referans52 Bennett IJ, Madden DJ. Disconnected aging: cerebral white matter integrity and age-related differences in cognition. Neuroscience. 2014; 276: 187–205.
  • Referans53 Peters A, Verderosa A, Sethares C. The neuroglial population in the primary visual cortex of the aging rhesus monkey. Glia. 2008; 56(11): 1151–1161.
  • Referans54 Peters A. The effects of normal aging on myelinated nerve fibers in monkey central nervous system. Front Neuroanat. 2009; 3: 11.
  • Referans55 Shook BA, Lennington JB, Acabchuk RL, et al. Ventriculomegaly associated with ependymal gliosis and declines in barrier integrity in the aging human and mouse brain. Aging Cell. 2014; 13: 340–350.
  • Referans56 Pfefferbaum A, Mathalon DH, Sullivan EV, et al. A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Arch Neurol. 1994; 51(9): 874–887.
  • Referans57 Resnick SM, Goldszal AF, Davatzikos C, et al. One-year age changes in MRI brain volumes in older adults. Cereb Cortex. 2000; 10(5): 464-72.
  • Referans58 Riddle DR, Sonntag WE, Lichtenwalner RJ. Microvascular plasticity in aging. Ageing Res Rev. 2003; 2(2): 149–168.
  • Referans59 Brown WR, Thore CR. Review: cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol Appl Neurobiol. 2011; 37(1): 56-74.
  • Referans60 Isaev NK, Stelmashook EV, Genrikhs EE. Neurogenesis and brain aging. Rev Neurosci. 2019; 30(6): 573-580.
  • Referans61 Galvan V, Jin K. Neurogenesis in the aging brain. Clin Interv Aging. 2007; 2(4): 605-10.
  • Referans62 Ahlenius H, Visan V, Kokaia M, et al. Neural stem and progenitor cells retain their potential for proliferation and differentiation into functional neurons despite lower number in aged brain. J Neurosci. 2009; 29(14): 4408-19.
  • Referans63 Enwere E, Shingo T, Gregg C, et al. Aging Results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci. 2004; 24: 8354–8365.
  • Referans64 Zhang H, Li J, Ren J, et al. Single-nucleus transcriptomic landscape of primate hippocampal aging. Protein Cell. 2021; 12(9): 695–716.
  • Referans65 Mahncke HW, Bronstone A, Merzenich MM. Brain plasticity and functional losses in the aged: scientific bases for a novel intervention. Prog Brain Res. 2006; 157: 81-109.
  • Referans66 Caserta MT, Bannon Y, Fernandez F, et al. Normal brain aging clinical, immunological, neuropsychological, and neuroimaging features. Int Rev Neurobiol. 2009; 84: 1-19.
  • Referans67 Lee P, Kim J, Williams R, et al. Effects of aging on blood brain barrier and matrix metalloproteases following controlled cortical impact in mice. Exp Neurol. 2012; 234(1): 50-61.
  • Referans68 Elahy M, Jackaman C, Mamo JC, et al. Blood-brain barrier dysfunction developed during normal aging is associated with inflammation and loss of tight junctions but not with leukocyte recruitment. Immun Ageing. 2015;12: 2.
  • Referans69 Henry CJ, Huang Y, Wynne AM, Godbout JP. Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1beta and anti-inflammatory IL-10 cytokines. Brain Behav Immun. 2009; 23(3): 309-17.
  • Referans70 Perry VH, Matyszak MK, Fearn S. Altered antigen expression of microglia in the aged rodent CNS. Glia. 1993; 7(1): 60-7.
  • Referans71 Stichel CC, Luebbert H. Inflammatory processes in the aging mouse brain: participation of dendritic cells and T-cells. Neurobiol Aging. 2007; 28(10): 1507-21.
  • Referans72 Letiembre M, Hao W, Liu Y, et al. Innate immune receptor expression in normal brain aging. Neuroscience. 2007; 146(1): 248-54.
  • Referans73 Griffin R, Nally R, Nolan Y, et al. The age-related attenuation in long-term potentiation is associated with microglial activation. J Neurochem. 2006; 99(4): 1263-72.
  • Referans74 Griciuc A, Serrano-Pozo A, Parrado AR, et al. Alzheimer's disease risk gene CD33 inhibits microglial uptake of amyloid beta. Neuron. 2013; 78(4): 631-43.
  • Referans75 Li L, Xiong WC, Mei L. Neuromuscular junction formation, aging, and disorders. Annu Rev Physiol. 2018; 80: 159-188.
  • Referans76 Peters A. Structural changes that occur during normal aging of primate cerebral hemispheres. Neurosci Biobehav Rev. 2002; 26(7): 733-41.
  • Referans77 Panagiotou M, Michel S, Meijer JH, Deboer T. The aging brain: sleep, the circadian clock and exercise. Biochem Pharmacol. 2021; 191: 114563.
  • Referans78 Satoh A, Imai SI, Guarente L. The brain, sirtuins, and ageing. Nat Rev Neurosci. 2017; 18(6): 362-374.
  • Referans79 Hinman JD, Abraham CR. What's behind the decline? The role of white matter in brain aging. Neurochem Res. 2007; 32(12): 2023-31.
  • Referans80 Sloane JA, Hinman JD, Lubonia M, et al. Age-dependent myelin degeneration and proteolysis of oligodendrocyte proteins is associated with the activation of calpain-1 in the rhesus monkey. J Neurochem. 2003; 84(1): 157-68.
  • Referans81 Hinman JD, Peters A, Cabral H, et al. Age-related molecular reorganization at the node of Ranvier. J Comp Neurol. 2006; 495(4): 351-62.
  • Referans82 Ravera S, Bartolucci M, Cuccarolo P, et al. Oxidative stress in myelin sheath: The other face of the extramitochondrial oxidative phosphorylation ability. Free Radic Res. 2015; 49(9): 1156-64.
  • Referans83 Mavroudis IA, Manani MG, Petrides F, et al. Age-related dendritic and spinal alterations of pyramidal cells of the human visual cortex. Folia Neuropathol. 2015; 53(2): 100-10.
  • Referans84 Liu RH, Bertolotto C, Engelhardt JK, Chase MH. Age-related changes in soma size of neurons in the spinal cord motor column of the cat. Neurosci Lett. 1996; 211(3): 163-6.
  • Referans85 Stahon KE, Bastian C, Griffith S, et al. Age-Related Changes in Axonal and Mitochondrial Ultrastructure and Function in White Matter. J Neurosci. 2016; 36(39): 9990-10001.
  • Referans86 Fan Z, Bin L. Will Sirtuin 2 Be a Promising Target for Neuroinflammatory Disorders? Front. Cell. Neurosci. 2022; 16:915587.
  • Referans87 Herskovits AZ, Guarente L. SIRT1 in neurodevelopment and brain senescence. Neuron. 2014; 81(3): 471-83.
  • Referans88 Gao J, Wang WY, Mao YW, et al. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature. 2010; 466(7310): 1105-9.
  • Referans89 Michán S, Li Y, Chou MM, et al. SIRT1 is essential for normal cognitive function and synaptic plasticity. J Neurosci. 2010; 30(29): 9695-707.
  • Referans90 Jiang M, Wang J, Fu J, et al. Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets. Nat Med. 2011; 18(1): 153-8.
  • Referans91 Jeong H, Cohen DE, Cui L, et al. Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway. Nat Med. 2011; 18(1): 159-65.
  • Referans92 Puigoriol-Illamola D, Martínez-Damas M, Griñán-Ferré C, Pallàs M. Chronic Mild stress modified epigenetic mechanisms leading to accelerated senescence and impaired cognitive performance in mice. Int J Mol Sci. 2020; 21(3): 1154.
  • Referans93 Lu W, Wang Q, Xu C, et al. SUMOylation is essential for Sirt2 tumor-suppressor function in neuroblastoma. Neoplasia. 2021; 23(1):129-139.
  • Referans94 Diaz-Perdigon T, Belloch FB, Ricobaraza A, et al. Early sirtuin 2 inhibition prevents age-related cognitive decline in a senescence-accelerated mouse model. Neuropsychopharmacology. 2020; 45(2): 347-357.
  • Referans95 Outeiro TF, Kontopoulos E, Altmann SM, et al. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science. 2007; 317(5837): 516-9.
  • Referans96 Ramadori G, Coppari R. Does hypothalamic SIRT1 regulate aging?. Aging (Albany NY). 2011; 3: 325-328.
  • Referans97 Cho SH, Chen JA, Sayed F, et al. SIRT1 deficiency in microglia contributes to cognitive decline in aging and neurodegeneration via epigenetic regulation of IL-1β. J Neurosci. 2015; 35(2): 807-18.
  • Referans98 Pais TF, Szegő ÉM, Marques O, et al. The NAD-dependent deacetylase sirtuin 2 is a suppressor of microglial activation and brain inflammation. EMBO J. 2013; 32(19): 2603-16.
  • Referans99 Dai SH, Chen T, Wang YH, et al. Sirt3 protects cortical neurons against oxidative stress via regulating mitochondrial Ca2+ and mitochondrial biogenesis. Int J Mol Sci. 2014; 15(8): 14591-609.
  • Referans100 Someya S, Yu W, Hallows WC, et al. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell. 2010; 143(5): 802-12.
  • Referans101 Satoh A, Imai S. Systemic regulation of mammalian ageing and longevity by brain sirtuins. Nat Commun. 2014; 5: 4211.
  • Referans102 Aging Biomarker Consortium, Bao H, Cao J, et al. Biomarkers of aging. Sci China Life Sci. 2023; 66: 893-1066.
Toplam 100 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Halk Sağlığı (Diğer)
Bölüm Derlemeler
Yazarlar

Damla Gündüz 0000-0003-4838-6574

Oya Korkmaz 0000-0003-2923-5869

Yayımlanma Tarihi 20 Mart 2025
Gönderilme Tarihi 29 Haziran 2024
Kabul Tarihi 26 Ağustos 2024
Yayımlandığı Sayı Yıl 2025 Cilt: 2 Sayı: 3

Kaynak Göster

APA Gündüz, D., & Korkmaz, O. (2025). İnsanlarda yaşlanmanın beyin üzerindeki etkisi: Kapsamlı bir inceleme. Turkish Journal of Healthy Aging Medicine, 2(3), 8-21. https://doi.org/10.5281/zenodo.15055863