Yetişkin Nörogenezi Ekseninde Aralıklı Oruç ve Kalori Kısıtlamasının Nörodejeneratif Hastalıkları Önlemede Rolü

Öz

Yaşlanma, Alzheimer, Parkinson ve Huntington hastalıkları gibi nörodejeneratif hastalıkların en önemli risk faktörü olarak değerlendirilmektedir. Dahası düzensiz nörogenezin de nörodejeneratif hastalıkların sebeplerinden biri olabileceği yorumlanmaktadır. Nörogenezi, sinaptik plastisiteyi ve hücre sağ kalımını teşvik ederek beynin gelişiminde ve plastisitesinde önemli rol oynadığı bilinen bir büyüme faktörü olan beyin türevli nörotrofik faktör sinyalinin yaşlanma ile birlikte beyinde azaldığını ve nörodejenaratif hastalıkların sebebi olabileceğini ortaya koyan çalışmalar vardır. Bir beslenme metodu olan aralıklı oruç veya kalori kısıtlamasının insan ve kemirgen beyninin çeşitli bölgelerinde beyin türevli nörotrofik faktör ekspresyonunu arttırdığı bulgulanmıştır. Bu durum bize, yaşa bağlı azalma gösteren beyin türevli nörotrofik faktörün beslenme düzeni ile zenginleştirilebilecek bir nörotrofin olabileceğinin sinyalini vermektedir. Buradan hareketle söz konusu beslenme metotlarının beyin türevli nörotrofik faktörü sinyalleyerek yetişkin hipokampal nörogenezini tetiklemesi ve beynin öğrenme, hafıza ve ruh halini kontrol eden hipokampus alanında değişiklikler yaparak, yaşlanmaya karşı beynin direncini nasıl etkilediği araştırılmıştır. İnsan ve hayvan çalışmalarından elde edilen önemli kanıtlar, aralıklı oruç ve kalori kısıtlamasının beyin yaşlanması üzerindeki yararlı etkilerinde beyin türevli nörotrofik faktörün sinyallemesinin rol oynadığını ve bunun da nörodejeneratif hastalıkları önlemede fonksiyonel bir sonuç vaat etmesi açısından önemini ortaya koymaktadır.

Anahtar Kelimeler

• Yetişkin Nörogenezi
• Aralıklı Oruç
• Kalori Kısıtlaması
• Nörodejeneratif Hastalıklar

The Role of Intermittent Fasting and Calorie Restriction in Preventing Neurodegenerative Diseases within the Context of Adult Neurogenesis

Öz

Aging is considered the most important risk factor for neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases. Moreover, it is interpreted that irregular neurogenesis may also be one of the causes of neurodegenerative diseases. The brain-derived neurotrophic factor signal, a growth factor known to play an important role in the development and plasticity of the brain by promoting neurogenesis, synaptic plasticity and cell survival, decreases in the brain with aging and may be the cause of neurodegenerative diseases. Intermittent fasting or calorie restriction, a nutritional method, increases brain-derived neurotrophic factor expression in various regions of the human and rodent brain. This brings to mind the question of whether nutritional methods such as intermittent fasting and calorie restriction may play a role in preventing neurodegenerative diseases. Based on this, it has been investigated how these nutritional methods trigger adult hippocampal neurogenesis by signaling brain-derived neurotrophic factor and how they affect the brain's resistance to aging by causing changes in the hippocampus area of the brain that controls learning, memory and mood. Significant evidence obtained from human and animal studies reveals that brain-derived neurotrophic factor signaling plays a role in the beneficial effects of intermittent fasting and calorie restriction on brain aging and that this is important in terms of promising a functional result in preventing neurodegenerative diseases.

Anahtar Kelimeler

• Adult Neurogenesis
• Intermittent Fasting
• Calorie Restriction
• Neurodegenerative Disorders

Kaynakça

1. Alomari MA, Khalil H, Khabour OF, Alzoubi KH, Dersieh EH (2018) Altered cardiovascular function is related to reduced BDNF in Parkinson’s disease. Exp Aging Res, 44:232-245.
2. Anacker C, Hen R (2017) Adult hippocampal neurogenesis and cognitive flexibility—linking memory and mood. Nat Rev Neurosci, 18:335-346.
3. Andika FR, Yoon JH, Kim GS, Jeong Y (2021) Intermittent fasting alleviates cognitive impairments and hippocampal neuronal loss but enhances astrocytosis in mice with subcortical vascular dementia. J Nutr, 151:722-730.
4. Ansari A, Thibault PA, Salapa HE, Clarke JP, Levin MC (2025) Mutations in hnRNP A1 drive neurodegeneration and alternative RNA splicing of neuronal gene targets. Neurobiol Dis, 206:106814.
5. Anson RM, Guo Z, de Cabo R, Iyun T, Rios M, Hagepanos A et al. (2003) Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci U S A, 100:6216-6220.
6. Apple DM, Mahesula S, Fonseca RS, Zhu C, Kokovay E (2019) Calorie restriction protects neural stem cells from age-related deficits in the subventricular zone. Aging (Albany NY), 11:115-126.
7. Arumugam TV, Phillips TM, Cheng A, Morrell CH, Mattson MP, Wan R (2010) Age and energy intake interact to modify cell stress pathways and stroke outcome. Ann Neurol, 67:41-52.
8. Baik SH, Rajeev V, Fann DYW, Jo DG, Arumugam TV (2020) Intermittent fasting increases adult hippocampal neurogenesis. Brain Behav, 10:e01444.

9. Barnabé-Heider F, Miller FD (2003) Endogenously produced neurotrophins regulate survival and differentiation of cortical progenitors via distinct signaling pathways. J Neurosci, 23:5149-5160.
10. Bayrak E, Serter R, Işıklı S. (2020) Duygusal, dışsal ve kısıtlayıcı yeme bozukluklarının metabolik sendrom gelişimi üzerine etkisi. Ankara Hastanesi Tıp Dergisi, 53:36-43.
11. Benraiss A, Chmielnicki E, Lerner K, Roh D, Goldman SA (2001) Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain. J Neurosci, 21:6718-6731.
12. Bettio LE, Rajendran L, Gil-Mohapel J (2017) The effects of aging in the hippocampus and cognitive decline. Neurosci Biobehav Rev, 79:66-86.
13. Bondi MW, Edmonds EC, Salmon DP (2017) Alzheimer’s disease: past, present, and future. J Int Neuropsychol Soc, 23:818-831.
14. Bondolfi L, Ermini F, Long JM, Ingram DK, Jucker M (2004) Impact of age and caloric restriction on neurogenesis in the dentate gyrus of C57BL/6 mice. Neurobiol Aging, 25:333-340.
15. Brown ES, Rush AJ, McEwen BS (1999) Hippocampal remodeling and damage by corticosteroids: implications for mood disorders. Neuropsychopharmacology, 21:474-484.
16. Campêlo CL, Santos JR, Silva AF, Dierschnabel AL., Pontes A, Cavalcante JS et al. (2017) Exposure to an enriched environment facilitates motor recovery and prevents short-term memory impairment and reduction of striatal BDNF in a progressive pharmacological model of parkinsonism in mice. Behav Brain Res, 328:138-148.
17. Cao S, Li M, Sun Y, Wu P, Yang W, Dai H, et al. (2022) Intermittent fasting enhances hippocampal NPY expression to promote neurogenesis after traumatic brain injury. Nutrition, 97:111621.
18. Cheng A, Wang S, Cai J, Rao MS, Mattson MP (2003) Nitric oxide acts in a positive feedback loop with BDNF to regulate neural progenitor cell proliferation and differentiation in the mammalian brain. Dev Biol, 258:319-333.
19. Chi H, Chang HY, Sang TK (2018) Neuronal cell death mechanisms in major neurodegenerative diseases. Int J Mol Sci, 19:3082.
20. Church FC (2021) Treatment options for motor and non-motor symptoms of Parkinson’s disease. Biomolecules, 11:612.
21. Connor B, Young D, Yan Q, Faull RLM, Synek B, Dragunow M (1997) Brain-derived neurotrophic factor is reduced in Alzheimer's disease. Mol Brain Res, 49:71-81.
22. Culig L, Chu X, Bohr VA (2022) Neurogenesis in aging and age-related neurodegenerative diseases. Ageing Res Rev, 78:101636.
23. De Cabo R, Mattson MP (2019) Effects of intermittent fasting on health, aging, and disease. N Engl J Med, 381:2541-2551.
24. Dorsey ER, George BP, Leff B, Willis AW (2013) The coming crisis: obtaining care for the growing burden of neurodegenerative conditions. Neurology, 80:1989-1996.
25. Duan W, Guo Z, Jiang H, Ware M, Li XJ, Mattson MP (2003) Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice. Proc Nat Acad Sci U S A, 100:2911-2916.
26. Duan W, Guo Z, Mattson MP (2001) Brain‐derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice. J Neurochem, 76:619-626.
27. Duan W, Mattson MP (1999) Dietary restriction and 2‐deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson's disease. J Neurosci Res, 57:195-206.
28. Erbaba B, Arslan-Ergul A, Adams MM (2021) Effects of caloric restriction on the antagonistic and integrative hallmarks of aging. Ageing Res Rev, 66:101228.
29. Ferrer I, Goutan E, Marın C, Rey MJ, Ribalta T (2000) Brain-derived neurotrophic factor in Huntington disease. Brain Res, 866:257-261.
30. Franzmeier N, Ren J, Damm A, Monté-Rubio G, Boada M, Ruiz A et al. (2021) The BDNF Val66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer’s disease. Mol Psychiatry, 26:614-628.
31. Fu Y, Yu Y, Paxinos G, Watson C, Rusznák Z (2015) Aging-dependent changes in the cellular composition of the mouse brain and spinal cord. Neuroscience, 290:406-420.
32. Fusco S, Pani G (2013) Brain response to calorie restriction. Cell Mol Life Sci, 70:3157-3170.
33. Garcia-Gorro C, Garau-Rolandi M, Escrichs A, Rodriguez-Dechich N, Vaquer I, Subira S et al. (2019) An active cognitive lifestyle as a potential neuroprotective factor in Huntington's disease. Neuropsychologia, 122:116-124.
34. Gil-Mohapel J, Simpson JM, Ghilan M, Christie BR (2011) Neurogenesis in Huntington's disease: can studying adult neurogenesis lead to the development of new therapeutic strategies? Brain Res, 1406:84-105.
35. Gilmore JL, Yi X, Quan L, Kabanov AV (2008) Novel nanomaterials for clinical neuroscience. J Neuroimmune Pharmacol, 3:83-94.
36. Go J, Park TS, Han GH, Park HY, Ryu YK, Kim YH et al. (2018). Piperlongumine decreases cognitive impairment and improves hippocampal function in aged mice. Int J Mol Med, 42:1875-1884.
37. Gorelick PB, Scuteri A, Black SE, DeCarli C, Greenberg SM, Iadecola C (2011) Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke, 42:2672-2713.
38. Jahn H (2013) Memory loss in Alzheimer's disease. Dialogues Clin Neurosci, 15:445-454.
39. Hagg T (2009) From neurotransmitters to neurotrophic factors to neurogenesis. Neuroscientist, 15:20-27.
40. Halagappa VKM, Guo Z, Pearson M, Matsuoka Y, Cutler RG, LaFerla FM, Mattson MP (2007) Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease. Neurobiol Dis, 26:212-220.
41. Hayashi M, Mistunaga F, Ohira K, Shimizu K (2001) Changes in BDNF-immunoreactive structures in the hippocampal formation of the aged macaque monkey. Brain Res, 918:191-196.
42. Hsieh J. (2012) Orchestrating transcriptional control of adult neurogenesis. Genes Dev, 26:1010-1021.
43. Holtzman DM, Morris JC, Goate AM (2011) Alzheimer’s disease: the challenge of the second century. Sci Transl Med, 3:77sr1.
44. Horgusluoglu E, Nudelman K, Nho K, Saykin AJ (2017) Adult neurogenesis and neurodegenerative diseases: A systems biology perspective. Am J Med Genet B Neuropsychiatr Genet, 174:93-112.
45. Hornsby AK, Redhead YT, Rees DJ, Ratcliff MS, Reichenbach A, Wells T, et al. (2016) Short-term calorie restriction enhances adult hippocampal neurogenesis and remote fear memory in a Ghsr-dependent manner. Psychoneuroendocrinology, 63:198-207.
46. Hou Y, Dan X, Babbar M, Wei Y, Hasselbalch S G, Croteau D L et al. (2019) Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol, 15:565-581.
47. Hou Y, Lautrup S, Cordonnier S, Wang Y, Croteau DL, Zavala E (2018) NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. Proc Natl Acad Sci U S A, 115:E1876-E1885.
48. Hu Y, Yang Y, Zhang M, Deng M, Zhang JJ (2017) Intermittent fasting pretreatment prevents cognitive impairment in a rat model of chronic cerebral hypoperfusion. J Nutr, 147:1437-1445.
49. Jack JCR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB et al. (2018) NIA‐AA research framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement, 14:535-562.
50. Kandasamy M, Couillard-Despres S, Raber KA, Stephan M, Lehner B, Winner B, (2010) Stem cell quiescence in the hippocampal neurogenic niche is associated with elevated transforming growth factor-β signaling in an animal model of Huntington disease. J Neuropathol Exp Neurol, 69:717-728.
51. Katoh‐Semba R, Takeuchi IK, Semba R, Kato K (1997) Distribution of brain‐derived neurotrophic factor in rats and its changes with development in the brain. J. Neurochem. 69:34-42.
52. Kaptan Z, Akgün-Dar K, Kapucu A, Dedeakayoğulları H, Batu Ş, Üzüm G (2015) Long term consequences on spatial learning-memory of low-calorie diet during adolescence in female rats; hippocampal and prefrontal cortex BDNF level, expression of NeuN and cell proliferation in dentate gyrus. Brain Res, 1618:194-204.
53. Khalil B, El Fissi N, Aouane A, Cabirol-Pol MJ, Rival T, Liévens JC (2015) PINK1-induced mitophagy promotes neuroprotection in Huntington’s disease. Cell Death Dis, 6:e1617.
54. Kim C, Pinto AM, Bordoli C, Buckner LP, Kaplan PC, Del Arenal IM, et al. (2020) Energy restriction enhances adult hippocampal neurogenesis-associated memory after four weeks in an adult human population with central obesity; a randomized controlled trial. Nutrients, 12:638.
55. Kuhla A, Lange S, Holzmann C, Maass F, Petersen J, Vollmar B (2013) Lifelong caloric restriction increases working memory in mice. PloS one, 8:e68778.
56. Lazarov O, Mattson MP, Peterson DA, Pimplikar SW, van Praag H (2010) When neurogenesis encounters aging and disease. Trends Neurosci, 33:569-579.
57. Le Grand JN, Gonzalez-Cano L, Pavlou MA, Schwamborn JC (2015) Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression. Cell Mol Life Sci, 72:773-797.
58. Leal PC, Lins LC, De Gois AM, Marchioro M, Santos JR (2016) Commentary: evaluation of models of Parkinson's disease. Front. Neurosci, 10:283.
59. Leão AH, Sarmento‐Silva AJ, Santos JR, Ribeiro AM, Silva RH (2015) Molecular, neurochemical, and behavioral hallmarks of reserpine as a model for Parkinson's disease: new perspectives to a long‐standing model. Brain Pathol, 25:377-390.
60. Lee J, Duan W, Long JM, Ingram DK, Mattson MP (2000) Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats. J Mol Neurosci, 15:99-108.
61. Lee J, Duan W, Mattson MP (2002) Evidence that brain‐derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J Neurochem, 82:1367-1375.
62. Levi O, Michaelson DM (2007) Environmental enrichment stimulates neurogenesis in apolipoprotein E3 and neuronal apoptosis in apolipoprotein E4 transgenic mice. J Neurochem, 100:202-210.
63. Li W, Wu M, Zhang Y, Wei X, Zang J, Liu Y, et al. (2020) Intermittent fasting promotes adult hippocampal neuronal differentiation by activating GSK‐3β in 3xTg‐AD mice. J Neurochem, 155:697-713.
64. Lim J, Bang Y, Choi HJ (2018) Abnormal hippocampal neurogenesis in Parkinson’s disease: relevance to a new therapeutic target for depression with Parkinson’s disease. Arch Pharm Res, 41:943-954.
65. Longo VD, Mattson MP (2014) Fasting: molecular mechanisms and clinical applications. Cell Metab, 19:181-192.
66. Luo Y, Kuang S, Li H, Ran D, Yang J (2017) cAMP/PKA-CREB-BDNF signaling pathway in hippocampus mediates cyclooxygenase 2-induced learning/memory deficits of rats subjected to chronic unpredictable mild stress. Oncotarget, 8:35558-35572.
67. MacMillan KS, Naidoo J, Liang J, Melito L, Williams NS, Morlock L et al. (2011) Development of proneurogenic, neuroprotective small molecules. J Am Chem Soc, 133:1428-1437.
68. Marosi K, Mattson MP (2014) BDNF mediates adaptive brain and body responses to energetic challenges. Trends Endocrinol Metab, 25:89-98.
69. Martin B, Mattson MP, Maudsley S (2006) Caloric restriction and intermittent fasting: two potential diets for successful brain aging. Ageing Res Rev, 5:332-353.
70. Massa F, Koehl M, Wiesner T, Grosjean N, Revest JM, Piazza PV, et al. (2011) Conditional reduction of adult neurogenesis impairs bidirectional hippocampal synaptic plasticity. Proc Natl Acad Sci U S A, 108:6644-6649.
71. Mattson MP (2003) Gene–diet interactions in brain aging and neurodegenerative disorders. Ann Intern Med, 139(5 Pt 2):441-444.
72. Mattson MP (2019) An evolutionary perspective on why food overconsumption impairs cognition. Trends Cogn Sci, 23:200-212.
73. Mattson MP, Duan W, Guo Z (2003) Meal size and frequency affect neuronal plasticity and vulnerability to disease: cellular and molecular mechanisms. J Neurochem, 84:417-431.
74. Mattson MP, Longo VD, Harvie M (2017) Impact of intermittent fasting on health and disease processes. Ageing Res Rev, 39:46-58.
75. Mattson MP, Maudsley S, Martin B (2004) BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci, 27:589-594.
76. Mattson MP, Wan R (2005) Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems. J Nutr Biochem, 16:129-137.
77. Mayor E (2023) Neurotrophic effects of intermittent fasting, calorie restriction and exercise: a review and annotated bibliography. Front Aging, 4:1161814. McCay C M, Crowell M F, Maynard L A (1935). The effect of retarded growth upon the length of life span and upon the ultimate body size: one figure. J Nutr, 10:63-79.
78. McGregor MM, Nelson AB (2019) Circuit mechanisms of Parkinson’s disease. Neuron, 101:1042-1056.
79. Medina A, Mahjoub Y, Shaver L, Pringsheim T (2022). Prevalence and incidence of Huntington's disease: an updated systematic review and meta‐analysis. Mov Disord, 37:2327-2335.
80. Mendonça MS, Melo JE, Franco HS, Bispo JM, Luz AC, Souza JL et al. (2025) Patterns of BDNF expression in the dorsal striatum and cognitive processing areas during aging in a progressive model of parkinsonism. Brain Mech, 144:202485.
81. Melgar-Locatelli S, Rodriguez-Pérez C, Castilla-Ortega E, Castro-Zavala A, Rivera P (2023) Nutrition and adult neurogenesis in the hippocampus: Does what you eat help you remember? Front Neurosci, 17:1147269.
82. Miao Z, Wang Y, Sun Z (2020) The relationships between stress, mental disorders, and epigenetic regulation of BDNF. Int J Mol Sci, 21:1375.
83. Michalski B, Corrada MM, Kawas CH, Fahnestock M (2015) Brain-derived neurotrophic factor and TrkB expression in the “oldest-old,” the 90+ Study: correlation with cognitive status and levels of soluble amyloid-beta. Neurobiol Aging, 36:3130-3139.
84. Miranda M, Morici JF, Zanoni MB, Bekinschtein P (2019) Brain-derived neurotrophic factor: a key molecule for memory in the healthy and the pathological brain. Front Cell Neurosci, 13:472800.
85. Mu Y, Lee SW, Gage FH (2010) Signaling in adult neurogenesis. Curr Opin Neurobiol, 20:416-423.
86. Murphy T, Dias GP, Thuret S (2014) Effects of diet on brain plasticity in animal and human studies: mind the gap. Neural Plast, 2014:563160.
87. Nieto RR, Silva H, Armijo A, Nachar R, González A, Castañeda C (2023) BDNF and cognitive function in Chilean schizophrenic patients. Int J Mol Sci, 24:10569.
88. Obeso JA, Stamelou M, Goetz CG, Poewe W, Lang AE, Weintraub D, et al. (2017) Past, present, and future of Parkinson's disease: A special essay on the 200th Anniversary of the Shaking Palsy. Mov Disord, 32:1264-1310.
89. Ortega-Martínez S (2015) Influences of prenatal and postnatal stress on adult hippocampal neurogenesis: the double neurogenic niche hypothesis. Behav Brain Res, 281:309-317.
90. Pandey S, Singh B, Yadav SK, Mahdi AA (2018) Novel biomarker for neurodegenerative diseases-motor neuron disease (MND), cerebellar ataxia (CA) and Parkinson's disease (PD). Clin Chim Acta, 485:258-261.
91. Peng S, Wuu J, Mufson EJ, Fahnestock M (2005) Precursor form of brain‐derived neurotrophic factor and mature brain‐derived neurotrophic factor are decreased in the pre‐clinical stages of Alzheimer's disease. J Neurochem, 93:1412-1421.
92. Qi S, Yin P, Wang L, Qu M, Kan GL, Zhang H et al. (2021) Prevalence of Parkinson's disease: A community‐based study in China. Mov Disord, 36:2940-2944.
93. Wang Q, Liu J, Guo Y, Dong G, Zou W, Chen Z (2019) Association between BDNF G196A (Val66Met) polymorphism and cognitive impairment in patients with Parkinson's disease: a meta-analysis. Braz J Med Biol Res, 52:e8443.
94. Raza C, Anjum R (2019) Parkinson's disease: Mechanisms, translational models and management strategies. Life Sci, 226:77-90.
95. Revest JM, Dupret D, Koehl M, Funk-Reiter C, Grosjean N, Piazza PV, et al. (2009) Adult hippocampal neurogenesis is involved in anxiety-related behaviors. Mol Psychiatry, 14:959-967.
96. Rothman SM, Griffioen KJ, Wan R, Mattson MP (2012) Brain‐derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health. Ann N Y Acad Sci, 1264:49-63.
97. Poulose SM, Miller MG, Scott T, Shukitt-Hale B (2017) Nutritional factors affecting adult neurogenesis and cognitive function. Adv Nutr, 8:804-811.
98. Re F, Gregori M, Masserini M (2012) Nanotechnology for neurodegenerative disorders. Maturitas, 73:45-51.
99. Schultz MB, Sinclair DA (2016) When stem cells grow old: phenotypes and mechanisms of stem cell aging. Development, 143:3-14.
100. Sevinçer GM, Coşkun H, Konuk N, Bozkurt S. (2014) Bariatrik cerrahinin psikiyatrik ve psikososyal yönleri. Psikiyatride Güncel Yaklaşımlar, 6:32-44.
101. Selman C (2014) Dietary restriction and the pursuit of effective mimetics. Proc Nutr Soc, 73:260-270.
102. Setel DD, Beker M, Terzioglu-Usak S, Elibol, B. (2022) Astragalus membranaceus treatment combined with caloric restriction may enhance genesis factors and decrease apoptosis in the hippocampus of rats. Arch Gerontol Geriatr, 99:104584.
103. Sibille KT, Bartsch F, Reddy D, Fillingim RB, Keil A (2016) Increasing neuroplasticity to bolster chronic pain treatment: a role for intermittent fasting and glucose administration? J Pain, 17:275-281.
104. Shefa U, Jeong NY, Song IO, Chung HJ, Kim D, Jung J, et al. (2019) Mitophagy links oxidative stress conditions and neurodegenerative diseases. Neural Regen Res, 14:749-756.
105. Shetty AK, Kodali M, Upadhya R, Madhu LN (2018) Emerging anti-aging strategies-scientific basis and efficacy. Aging Dis, 9:1165-1184.
106. Spolidoro M, Baroncelli L, Putignano E, Maya-Vetencourt JF, Viegi A, Maffei L (2011) Food restriction enhances visual cortex plasticity in adulthood. Nat Commun, 2:320.
107. Sung PS, Lin PY, Liu CH, Su HC, Tsai KJ (2020) Neuroinflammation and neurogenesis in Alzheimer’s disease and potential therapeutic approaches. Int J Mol Sci, 21:701.
108. Trepanowski JF, Canale RE, Marshall KE, Kabir MM, Bloomer RJ (2011) Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings. Nutr J, 10:107.
109. Tobin MK, Musaraca K, Disouky A, Shetti A, Bheri A, Honer WG et al. (2019) Human hippocampal neurogenesis persists in aged adults and Alzheimer’s disease patients. Cell Stem Cell, 24:974-982.
110. Toda T, Parylak SL, Linker SB, Gage FH (2019) The role of adult hippocampal neurogenesis in brain health and disease. Mol Psychiatry, 24:67-87.
111. Tolosa E, Garrido A, Scholz SW, Poewe W (2021) Challenges in the diagnosis of Parkinson's disease. Lancet Neurol, 20:385-397.
112. Vidyadhara DJ, Lee JE, Chandra SS (2019) Role of the endolysosomal system in Parkinson’s disease. J Neurochem, 150:487-506.
113. Villegas Pedraza NL, Chávez Montes A, Montiel Condado D, González Hernández B, González-Horta A (2014) Análisis funcional de oligómeros de alfa-sinucleína en la permeabilidad de membranas. Acta Bioquím Clín Latinoam, 48:437-445.
114. Wahl D, Solon-Biet SM, Wang QP, Wali JA, Pulpitel T, Clark X et al. (2018) Comparing the effects of low-protein and high-carbohydrate diets and caloric restriction on brain aging in mice. Cell Rep, 25:2234-2243.
115. Wassouf Z, Hentrich T, Samer S, Rotermund C, Kahle PJ, Ehrlich I et al. (2018) Environmental enrichment prevents transcriptional disturbances induced by alpha-synuclein overexpression. Front Cell Neurosci, 12:112.
116. Witte A V, Fobker M, Gellner R, Knecht S, Floel A. (2009) Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci U S A, 106:1255–1260.
117. Wood JD (2011) Enteric nervous system neuropathy: repair and restoration. Curr Opin Gastroenterol, 27:106-111. Xie H, Jiang Y, Zhang X, Min X, Zeng J, Chen L et al (2025) Corticosterone-induced postpartum depression induces depression-like behavior and impairs hippocampal neurogenesis in adolescent offspring via HPA axis and BDNF-mTOR pathway. Neurobiol Stress, 34:100708.
118. Zahra W, Rai SN, Birla H, Singh SS, Dilnashin H, Rathore AS et al. (2020) The global economic impact of neurodegenerative diseases: Opportunities and challenges In. Bioeconomy for Sustainable Development (Ed C Keswani):333-345. Cham, Springer
119. Zainuddin MSA, Thuret S (2012) Nutrition, adult hippocampal neurogenesis and mental health. Br Med Bull, 103:89-114.
120. Zhang K, Wang F, Zhai M, He M, Hu Y, Feng L (2023) Hyperactive neuronal autophagy depletes BDNF and impairs adult hippocampal neurogenesis in a corticosterone-induced mouse model of depression. Theranostics, 13:1059-1075.
121. Zhavoronkov A, Li R, Ma C, Mamoshina P (2019) Deep biomarkers of aging and longevity: from research to applications. Aging (Albany NY), 11:10771-10780.