Neuroscience of aging

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The neuroscience of aging is the study of the changes in the nervous system that occur with aging. Aging is associated with many changes in the central nervous system, such as mild atrophy of the cortex, which is considered non-pathological. Aging is also associated with many neurological and neurodegenerative diseases, such as amyotrophic lateral sclerosis, dementia, mild cognitive impairment, Parkinson's disease, and Creutzfeldt–Jakob disease. [1]

Contents

Normal structural and neural changes

Neurogenesis occurs very little in adults; it only occurs in the hypothalamus and striatum to a small extent in a process called adult neurogenesis. Environmental enrichment, physical activity and stress (which can stimulate or hinder this process) are key environmental and physiological factors affecting adult neurogenesis. [2] Sensory stimulation, social interactions, and cognitive challenges can describe an enriched environment. [3] Exercising has frequently increased the reproduction of neuronal precursor cells and helped with age-related declines in neurogenesis. The brain volume decreases roughly 5% per decade after forty. It is currently unclear why brain volume decreases with age. However, a few causes may include cell death, decreased cell volume, and changes in synaptic structure. The changes in brain volume are heterogeneous across regions, with the prefrontal cortex receiving the most significant reduction in volume, followed in order by the striatum, the temporal lobe, the cerebellar vermis, the cerebellar hemispheres, and the hippocampus. [4] However, one review found that the amygdala and ventromedial prefrontal cortex remained relatively free of atrophy, consistent with the finding of emotional stability occurring with non-pathological aging. [5] Enlargement of the ventricles, sulci and fissures is common in non-pathological aging. [6]

Changes may also be associated with neuroplasticity, synaptic functionality and voltage-gated calcium channels. [7] Increased hyperpolarization, possibly due to dysfunctional calcium regulation, decreases neuron firing rate and plasticity. This effect is particularly pronounced in the hippocampus of aged animals and may be an important contributor to age-associated memory deficits. The hyperpolarization of a neuron can be divided into three stages: fast, medium, and slow hyperpolarization. In aged neurons, the medium and slow hyperpolarization phases involve the prolonged opening of calcium-dependent potassium channels. The prolonging of this phase has been hypothesized to result from deregulated calcium and hypoactivity of cholinergic, dopaminergic, serotonergic and glutaminergic pathways. [8]

Normal functional changes

Episodic memory (remembering specific events) declines gradually from middle age, while semantic memory (general knowledge and facts) increases into early old age and then declines thereafter. [4] Older adults can exhibit reduced activity in specific brain regions during cognitive tasks, particularly in medial temporal areas related to memory processing. On the other hand, overrecruitment of other brain areas, mainly in the prefrontal cortex, can be engaged in memory-related tasks. [9] Older adults also tend to engage their prefrontal cortex more often during working memory tasks, possibly to compensate for executive functions. Further impairments of cognitive function associated with aging include decreased processing speed and inability to focus. A model proposed to account for altered activation posits that decreased neural efficiency driven by amyloid plaques and decreased dopamine functionality lead to compensatory activation. [10] Decreased processing of negative stimuli, as opposed to positive stimuli, appears in aging and becomes significant enough to detect even with autonomic nervous responses to emotionally charged stimuli. [11] Aging is also associated with decreased plantar reflex and Achilles reflex response. Nerve conductance also decreases during normal aging. [12]

DNA damage

DNA damage is a major risk factor in neurodegenerative diseases and in the decline of neuronal function with age. [13] Certain genes of the human frontal cortex display reduced transcriptional expression after age 40, especially after age 70. [14] In particular, genes with central roles in synaptic plasticity display reduced expression with age. The promoters of genes with reduced expression in the cortex of older individuals have a marked increase in DNA damage, likely oxidative DNA damage. [14]

Pathological changes

Roughly 20% of persons greater than 60 years of age have a neurological disorder, with episodic disorders being the most common, followed by extrapyramidal movement disorders and nerve disorders. [15] Diseases commonly associated with old age include

The misfolding of proteins is a common component of the proposed pathophysiology of many aging-related diseases. However, there is insufficient evidence to prove this. For example, the tau hypothesis for Alzheimer's proposes that tau protein accumulation results in the breakdown of neuron cytoskeletons, leading to Alzheimer's. [25] Another proposed mechanism for Alzheimer's is related to the accumulation of amyloid beta [26] in a similar mechanism to the prion propagation of Creutzfeldt-Jakob disease. Until a recent study, tau proteins were believed to be the precedents for Alzheimer's but in a combination of amyloid beta. [27] Similarly, the protein alpha-synuclein is hypothesized to accumulate in Parkinson's and related diseases. [28]

Chemo brain

Treatments with anticancer chemotherapeutic agents often are toxic to the cells of the brain, leading to memory loss and cognitive dysfunction that can persist long after the period of exposure. This condition, termed chemo brain, appears to be due to DNA damages that cause epigenetic changes in the brain that accelerate the brain aging process. [29]

Management

Treatment of an age-related neurological disease varies from disease to disease. Modifiable risk factors for dementia include diabetes, hypertension, smoking, hyperhomocysteinemia, hypercholesterolemia, and obesity (which are usually associated with many other risk factors for dementia). Paradoxically, drinking and smoking confer protection against Parkinson's disease. [30] [31] It also confers protective benefits to age-related neurological disease in the consumption of coffee or caffeine. [32] [33] [34] Consumption of fruits, fish and vegetables confers protection against dementia, as does a Mediterranean diet. [35] In animal experiments, long-term calorie restriction was found to help reduce oxidative DNA damage. [36] Physical exercise significantly lowers the risk of cognitive decline in old age [37] and is an effective treatment for those with dementia [38] [39] and Parkinson's disease. [40] [41] [42] [43]

References

  1. Brown, Rebecca C.; Lockwood, Alan H.; Sonawane, Babasaheb R. (8 January 2017). "Neurodegenerative Diseases: An Overview of Environmental Risk Factors". Environmental Health Perspectives. 113 (9): 1250–1256. doi:10.1289/ehp.7567. ISSN   0091-6765. PMC   1280411 . PMID   16140637.
  2. Klempin, Friederike; Kempermann, Gerd (2007-08-01). "Adult hippocampal neurogenesis and aging" . European Archives of Psychiatry and Clinical Neuroscience. 257 (5): 271–280. doi:10.1007/s00406-007-0731-5. ISSN   1433-8491. PMID   17401726.
  3. van Praag, Henriette; Kempermann, Gerd; Gage, Fred H. (December 2000). "Neural consequences of environmental enrichment" . Nature Reviews Neuroscience. 1 (3): 191–198. doi:10.1038/35044558. ISSN   1471-0048. PMID   11257907.
  4. 1 2 Peters, R (8 January 2017). "Ageing and the brain". Postgraduate Medical Journal. 82 (964): 84–88. doi:10.1136/pgmj.2005.036665. ISSN   0032-5473. PMC   2596698 . PMID   16461469.
  5. Mather, Mara (5 October 2015). "The Affective Neuroscience of Aging". Annual Review of Psychology. 67 (1): 213–238. doi:10.1146/annurev-psych-122414-033540. PMC   5780182 . PMID   26436717.
  6. LeMay, Marjorie (1984). "Radiologic Changes of the Aging Brain and Skull" (PDF). American Journal of Neuroradiology. 5: 269–275.
  7. Kelly, K. M.; Nadon, N. L.; Morrison, J. H.; Thibault, O.; Barnes, C. A.; Blalock, E. M. (1 January 2006). "The neurobiology of aging". Epilepsy Research. 68 (Suppl 1): S5–20. doi:10.1016/j.eplepsyres.2005.07.015. ISSN   0920-1211. PMID   16386406. S2CID   17123597.
  8. Kumar, Ashok; Foster, Thomas C. (1 January 2007). "Neurophysiology of Old Neurons and Synapses". Brain Aging: Models, Methods, and Mechanisms. Frontiers in Neuroscience. CRC Press/Taylor & Francis. ISBN   9780849338182. PMID   21204354.
  9. Grady, Cheryl L. (2008). "Cognitive Neuroscience of Aging" . Annals of the New York Academy of Sciences. 1124 (1): 127–144. Bibcode:2008NYASA1124..127G. doi:10.1196/annals.1440.009. ISSN   1749-6632. PMID   18400928.
  10. Reuter-Lorenz, Patricia A.; Park, Denise C. (8 January 2017). "Human Neuroscience and the Aging Mind: A New Look at Old Problems". The Journals of Gerontology Series B: Psychological Sciences and Social Sciences. 65B (4): 405–415. doi:10.1093/geronb/gbq035. ISSN   1079-5014. PMC   2883872 . PMID   20478901.
  11. Kaszniak, Alfred W.; Menchola, Marisa (1 January 2012). Behavioral neuroscience of emotion in aging. Current Topics in Behavioral Neurosciences. Vol. 10. pp. 51–66. doi:10.1007/7854_2011_163. ISBN   978-3-642-23874-1. ISSN   1866-3370. PMID   21910076.
  12. Stanton, Biba R. (1 February 2011). "The neurology of old age". Clinical Medicine. 11 (1): 54–56. doi:10.7861/clinmedicine.11-1-54. ISSN   1470-2118. PMC   5873804 . PMID   21404786.
  13. Delint-Ramirez I, Madabhushi R (January 2025). "DNA damage and its links to neuronal aging and degeneration". Neuron. 113 (1): 7–28. doi:10.1016/j.neuron.2024.12.001. PMID   39788088.
  14. 1 2 Lu T, Pan Y, Kao SY, Li C, Kohane I, Chan J, Yankner BA (June 2004). "Gene regulation and DNA damage in the ageing human brain". Nature. 429 (6994): 883–91. Bibcode:2004Natur.429..883L. doi:10.1038/nature02661. PMID   15190254. S2CID   1867993.
  15. Callixte, Kuate-Tegueu; Clet, Tchaleu Benjamin; Jacques, Doumbe; Faustin, Yepnjio; François, Dartigues Jean; Maturin, Tabue-Teguo (17 April 2015). "The pattern of neurological diseases in elderly people in outpatient consultations in Sub-Saharan Africa". BMC Research Notes. 8: 159. doi: 10.1186/s13104-015-1116-x . ISSN   1756-0500. PMC   4405818 . PMID   25880073.
  16. Bensimon G, Ludolph A, Agid Y, Vidailhet M, Payan C, Leigh PN (2008). "Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: The NNIPPS Study". Brain. 132 (Pt 1): 156–71. doi:10.1093/brain/awn291. PMC   2638696 . PMID   19029129.
  17. Carroll, William M. (2016). International Neurology. John Wiley & Sons. p. 188. ISBN   9781118777367.
  18. Mendez MF (November 2012). "Early-onset Alzheimer's disease: nonamnestic subtypes and type 2 AD". Archives of Medical Research. 43 (8): 677–85. doi:10.1016/j.arcmed.2012.11.009. PMC   3532551 . PMID   23178565.
  19. Vermeer SE, Koudstaal PJ, Oudkerk M, Hofman A, Breteler MM (January 2002). "Prevalence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study". Stroke. 33 (1): 21–5. doi: 10.1161/hs0102.101629 . PMID   11779883.
  20. Kiernan, MC; Vucic, S; Cheah, BC; Turner, MR; Eisen, A; Hardiman, O; Burrell, JR; Zoing, MC (12 March 2011). "Amyotrophic lateral sclerosis". Lancet. 377 (9769): 942–55. doi:10.1016/s0140-6736(10)61156-7. PMID   21296405. S2CID   14354178.
  21. Belay, Ermias D.; Schonberger, Lawrence B. (1 December 2002). "Variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy". Clinics in Laboratory Medicine. 22 (4): 849–862, v–vi. doi:10.1016/s0272-2712(02)00024-0. ISSN   0272-2712. PMID   12489284.
  22. Snowden, Julie S.; Neary, David; Mann, David M.A. (February 2002). "Frontotemporal dementia". Br J Psychiatry. 180 (2): 140–3. doi: 10.1192/bjp.180.2.140 . PMID   11823324.
  23. Dickson, Dennis; Weller, Roy O. (2011). Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders (2 ed.). John Wiley & Sons. p. 224. ISBN   9781444341232.
  24. "Corticobasal Degeneration Information Page: National Institute of Neurological Disorders and Stroke (NINDS)". Archived from the original on 2009-03-23. Retrieved 2009-03-20.
  25. Goedert, M.; Spillantini, M. G.; Crowther, R. A. (1 July 1991). "Tau proteins and neurofibrillary degeneration". Brain Pathology (Zurich, Switzerland). 1 (4): 279–286. doi: 10.1111/j.1750-3639.1991.tb00671.x . ISSN   1015-6305. PMID   1669718. S2CID   33331924.
  26. Hardy J, Allsop D (October 1991). "Amyloid Deposition as the Central Event in the Aetiology of Alzheimer's Disease". Trends in Pharmacological Sciences. 12 (10): 383–88. doi:10.1016/0165-6147(91)90609-V. PMID   1763432.
  27. Spires-Jones, Tara L.; Attems, Johannes; Thal, Dietmar Rudolf (2017-04-11). "Interactions of pathological proteins in neurodegenerative diseases". Acta Neuropathologica. 134 (2): 187–205. doi:10.1007/s00401-017-1709-7. ISSN   0001-6322. PMC   5508034 . PMID   28401333.
  28. Galpern, Wendy R.; Lang, Anthony E. (1 March 2006). "Interface between tauopathies and synucleinopathies: a tale of two proteins". Annals of Neurology. 59 (3): 449–458. doi:10.1002/ana.20819. ISSN   0364-5134. PMID   16489609. S2CID   19395939.
  29. Kovalchuk A, Kolb B (July 2017). "Chemo brain: From discerning mechanisms to lifting the brain fog-An aging connection". Cell Cycle. 16 (14): 1345–1349. doi:10.1080/15384101.2017.1334022. PMC   5539816 . PMID   28657421.
  30. Barranco Quintana, JL; Allam, MF; Del Castillo, AS; Navajas, RF (February 2009). "Parkinson's disease and tea: a quantitative review". Journal of the American College of Nutrition. 28 (1): 1–6. doi:10.1080/07315724.2009.10719754. PMID   19571153. S2CID   26605333.
  31. Jung, Se Young; Chun, Sohyun; Cho, Eun Bin; Han, Kyungdo; Yoo, Juhwan; Yeo, Yohwan; Yoo, Jung Eun; Jeong, Su Min; Min, Ju-Hong; Shin, Dong Wook (2023-09-13). "Changes in smoking, alcohol consumption, and the risk of Parkinson's disease". Frontiers in Aging Neuroscience. 15. doi: 10.3389/fnagi.2023.1223310 . ISSN   1663-4365. PMC   10525683 . PMID   37771519.
  32. Santos C, Costa J, Santos J, Vaz-Carneiro A, Lunet N (2010). "Caffeine intake and dementia: systematic review and meta-analysis". J. Alzheimers Dis. 20 (Suppl 1): S187–204. doi: 10.3233/JAD-2010-091387 . hdl: 10216/160619 . PMID   20182026.
  33. Marques S, Batalha VL, Lopes LV, Outeiro TF (2011). "Modulating Alzheimer's disease through caffeine: a putative link to epigenetics". J. Alzheimers Dis. 24 (2): 161–71. doi:10.3233/JAD-2011-110032. PMID   21427489.
  34. Arendash GW, Cao C (2010). "Caffeine and coffee as therapeutics against Alzheimer's disease". J. Alzheimers Dis. 20 (Suppl 1): S117–26. doi: 10.3233/JAD-2010-091249 . PMID   20182037.
  35. Lourida, Ilianna; Soni, Maya; Thompson-Coon, Joanna; Purandare, Nitin; Lang, Iain A.; Ukoumunne, Obioha C.; Llewellyn, David J. (July 2013). "Mediterranean Diet, Cognitive Function, and Dementia". Epidemiology. 24 (4): 479–489. doi: 10.1097/EDE.0b013e3182944410 . PMID   23680940. S2CID   19602773.
  36. Vitantonio, Ana T.; Dimovasili, Christina; Mortazavi, Farzad; Vaughan, Kelli L.; Mattison, Julie A.; Rosene, Douglas L. (2024-09-01). "Long-term calorie restriction reduces oxidative DNA damage to oligodendroglia and promotes homeostatic microglia in the aging monkey brain". Neurobiology of Aging. 141: 1–13. doi:10.1016/j.neurobiolaging.2024.05.005. ISSN   0197-4580. PMC  11318518. PMID   38788462.
  37. Andrade, Chittaranjan; Radhakrishnan, Rajiv (1 January 2009). "The prevention and treatment of cognitive decline and dementia: An overview of recent research on experimental treatments". Indian Journal of Psychiatry. 51 (1): 12–25. doi: 10.4103/0019-5545.44900 . ISSN   0019-5545. PMC   2738400 . PMID   19742190.
  38. Farina N, Rusted J, Tabet N (January 2014). "The effect of exercise interventions on cognitive outcome in Alzheimer's disease: a systematic review". Int Psychogeriatr. 26 (1): 9–18. doi: 10.1017/S1041610213001385 . PMID   23962667. S2CID   24936334.
  39. Rao AK, Chou A, Bursley B, Smulofsky J, Jezequel J (January 2014). "Systematic review of the effects of exercise on activities of daily living in people with Alzheimer's disease". Am J Occup Ther. 68 (1): 50–56. doi:10.5014/ajot.2014.009035. PMC   5360200 . PMID   24367955.
  40. Mattson MP (2014). "Interventions that improve body and brain bioenergetics for Parkinson's disease risk reduction and therapy". J Parkinsons Dis. 4 (1): 1–13. doi: 10.3233/JPD-130335 . PMID   24473219.
  41. Grazina R, Massano J (2013). "Physical exercise and Parkinson's disease: influence on symptoms, disease course and prevention". Rev Neurosci. 24 (2): 139–152. doi:10.1515/revneuro-2012-0087. PMID   23492553. S2CID   33890283.
  42. van der Kolk NM, King LA (September 2013). "Effects of exercise on mobility in people with Parkinson's disease". Mov. Disord. 28 (11): 1587–1596. doi:10.1002/mds.25658. PMID   24132847. S2CID   22822120.
  43. Tomlinson CL, Patel S, Meek C, Herd CP, Clarke CE, Stowe R, Shah L, Sackley CM, Deane KH, Wheatley K, Ives N (September 2013). "Physiotherapy versus placebo or no intervention in Parkinson's disease". Cochrane Database Syst Rev. 9 (9): CD002817. doi:10.1002/14651858.CD002817.pub4. PMC   7120224 . PMID   24018704.