age-associated changes in the central nervous system
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Introduction
The CNS undergoes change with aging.
Physiology
- small decrease in brain mass
- decreased brain blood flow
- impaired auto regulation of perfusion
- non random loss of neurons
- proliferation of astrocytes
- decreased ability of neurons to sprout axons or dendrites[7]
- decreased density of dentritic synapses
- scattered neurofibrillary tangles
- scattered senile plaques
- decreased myelin & total brain lipid
- slowed propagation of action potentials
- age-related damage to myelin sheaths, loss of axons, & reduction in white matter volume correlates with cognitive impairment[10]
- altered neurotransmitters
- dopamine
- serotonin
- increased monoamine oxidase (catecholamine metabolism)
- decreased hippocampal glucocorticoid receptors
- decrease in fluid intelligence
- slowed central processing & reaction time
- plasma contains factors that affect cognitive function[6][7][8][9]
- age-associated changes in the ventral visual cortex implicate diminished GABA with lesser ventral visual neural distinctiveness[12]
- age-associater increase in permeability of the blood-brain barrier[15]
- gene expression in the frontal cortex changes to reflect a cellular response to DNA damage, inflammation, mitochondrial dysfunction, oxidative stress, & altered insulin signaling[14]
- also see
- neuropsychiatric features of aging
- age-associated changes in sleep & role of the glymphatic system in removing waste products from the brain
Comparative biology
- plasma beta2 microglobulin (B2M) negatively regulates age-associated cognitive function in hippocampus of mice[8]
increased plasma eotaxin may inhibit learning, memory, & neurogenesis during aging in mice[9]
- age-associated increase in eotaxin in plasma levels in humans & mice[9]
- blood of young mice contains substances that reverse aging processes in heart muscle, skeletal muscle, & brain
- one of these substances is GDF11[6]
- brain-derived neurotrophic factor (BDNF) is the only gene altered at both mRNA & protein levels in rhesus monkeys[10]
- in brain macrophages, PGE2 levels rise with aging in mice[11]
- increase in PGE2 promotes sequestration of glucose into glycogen, reducing glucose flux & mitochondrial respiration.
- leads to neuroinflammation & cognitive decline
- inhibiting effect of PGE2 by either genetic or pharmacologic reverses brain dysfunction:
- synaptic proteins rise, mitochondrial function improves, neuroinflammation is reduced, & spatial memory deficits are reversed[11]
More general terms
More specific terms
Additional terms
- age-associated changes in sleep
- age-associated changes in the peripheral nervous system
- central nervous system
- central nervous system (CNS) disease
- seizures in the elderly
References
- ↑ Essentials of Clinical Geriatrics, 4th ed, Kane RL et al (eds) McGraw Hill, NY, 1999
- ↑ UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
- ↑ The Merck Manual of Geriatrics, 3rdh ed, Merck & Co, Rahway NJ, 2000
- ↑ Taffet GE, Physiology of Aging, In: Geriatric Medicine: An Evidence-Based Approach, 4th ed, Cassel CK et al (eds), Springer-Verlag, New York, 2003
- ↑ Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013 - ↑ 6.0 6.1 6.2 Katsimpardi L et al. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science 2014 May 9; 344:630. (http://dx.doi.org/10.1126/science.1251141) PMID: https://www.ncbi.nlm.nih.gov/pubmed/24797482
Villeda SA et al. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med 2014 May 4 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24793238 - ↑ 7.0 7.1 7.2 Bouchard J, Villeda SA Aging and brain rejuvenation as systemic events J Neurochem. 2015 Jan; 132(1): 5-19. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25327899
- ↑ 8.0 8.1 8.2 8.3 Smith LK, He Y, Park JS et al beta2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis. Nat Med. 2015 Jul 6. doi:http://dx.doi.org/ 10.1038/nm.3898. [Epub ahead of print] PMID: https://www.ncbi.nlm.nih.gov/pubmed/26147761
- ↑ 9.0 9.1 9.2 9.3 Villeda SA et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 2011 Sep; 477:90 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21886162
- ↑ 10.0 10.1 10.2 10.3 10.4 Robinson AA, Abraham CR, Rosene DL Candidate molecular pathways of white matter vulnerability in the brain of normal aging rhesus monkeys. GeroScience (2018) 40: 31 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29357021 Free PMC Article https://link.springer.com/article/10.1007/s11357-018-0006-2
- ↑ 11.0 11.1 11.2 Minhas PS, Latif-Hernandez A, McReynolds MR et al. Restoring metabolism of myeloid cells reverses cognitive decline in ageing. Nature 2021 Feb; 590:122 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33473210 https://www.nature.com/articles/s41586-020-03160-0
- ↑ 12.0 12.1 Chamberlain JC, Gagnon H, Lalwani P et al GABA levels in ventral visual cortex decline with age and are associated with neural distinctiveness. Neurobiology of Aging. 2021 Feb 26 Not indexed in PubMed https://www.sciencedirect.com/science/article/abs/pii/S0197458021000683
- ↑ Sikora E, Bielak-Zmijewska A, Dudkowska M Cellular Senescence in Brain Aging. Front. Aging Neurosci. 2021. 25 February PMID: https://www.ncbi.nlm.nih.gov/pubmed/33732142 PMCID: PMC7959760 Free PMC article https://www.frontiersin.org/articles/10.3389/fnagi.2021.646924/full
- ↑ 14.0 14.1 Mavrikaki M, Lee JD, Solomon IH, Slack FJ. Severe COVID-19 induces molecular signatures of aging in the human brain. medRxiv. 2021 Nov 24:2021.11.24.21266779. Preprint. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34845457 Free PMC article.
Mavrikaki M et al. Severe COVID-19 is associated with molecular signatures of aging in the human brain. Nat Aging 2022 Dec 5; [e-pub] Not indexed in PubMed https://www.nature.com/articles/s43587-022-00321-w - ↑ 15.0 15.1 Zeevi N, Pachter J, McCullough LD et al The blood-brain barrier: geriatric relevance of a critical brain-body interface. J Am Geriatr Soc. 2010 Sep;58(9):1749-57. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20863334 PMCID: PMC4667839 Free PMC article