Skip to main content Accessibility help
×
Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-23T09:50:24.279Z Has data issue: false hasContentIssue false

Chapter 3 - Cellular and Molecular Mechanisms for Age-Related Cognitive Decline

Published online by Cambridge University Press:  30 November 2019

Kenneth M. Heilman
Affiliation:
University of Florida
Stephen E. Nadeau
Affiliation:
University of Florida
Get access

Summary

Aging is often associated with a progressive decline of cognitive functions, due in part to the susceptibility of specific brain regions to stressors of aging. However, chronological age is a poor predictor of cognition. Cognitive decline is variable in terms of onset and progression, suggesting that biological age, due to differences in biological mechanisms that regulate vulnerability, is a better predictor of cognitive decline. As with humans, animal models exhibit variability in age-related cognitive decline, and this variability has been employed to determine biomarkers and mechanisms of cognitive impairment. Based on these animal models, theories of age-related cognitive decline have evolved. Recent work has focused on senescent physiology, rather than cell death associated with neurodegenerative disease. The results suggest that age-related alterations in redox stress modify Ca2+ regulation to alter learning and memory mechanisms, as well as signaling cascades from the synapse to the nucleus. Furthermore, the stressors of aging, senescent physiology, and environmental factors interact with epigenetic mechanisms contributing variability in gene transcription, resulting in variability in resiliency, onset, and the progression of the aging phenotype.

Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

de Flores, R, La Joie, R, Chetelat, G. Structural imaging of hippocampal subfields in healthy aging and Alzheimer’s disease. Neuroscience. 2015;309:2950.CrossRefGoogle ScholarPubMed
Kerchner, GA, Bernstein, JD, Fenesy, MC, Deutsch, GK, Saranathan, M, Zeineh, MM, et al. Shared vulnerability of two synaptically-connected medial temporal lobe areas to age and cognitive decline: a seven tesla magnetic resonance imaging study. J Neurosci. 2013;33(42):16666–72.CrossRefGoogle ScholarPubMed
Kirchhoff, BA, Gordon, BA, Head, D. Prefrontal gray matter volume mediates age effects on memory strategies. Neuroimage. 2014;90:326–34.Google Scholar
Raz, N, Gunning, FM, Head, D, Dupuis, JH, McQuain, J, Briggs, SD, et al. Selective aging of the human cerebral cortex observed in vivo: differential vulnerability of the prefrontal gray matter. Cereb Cortex. 1997;7(3):268–82.Google Scholar
Salat, DH, Buckner, RL, Snyder, AZ, Greve, DN, Desikan, RS, Busa, E, et al. Thinning of the cerebral cortex in aging. Cereb Cortex. 2004;14(7):721–30.Google Scholar
Wolf, D, Fischer, FU, de Flores, R, Chetelat, G, Fellgiebel, A. Differential associations of age with volume and microstructure of hippocampal subfields in healthy older adults. Hum Brain Mapp. 2015;36(10):3819–31.CrossRefGoogle ScholarPubMed
Raz, N, Ghisletta, P, Rodrigue, KM, Kennedy, KM, Lindenberger, U. Trajectories of brain aging in middle-aged and older adults: regional and individual differences. Neuroimage. 2010;51(2):501–11.Google Scholar
Jackson, TC, Rani, A, Kumar, A, Foster, TC. Regional hippocampal differences in AKT survival signaling across the lifespan: implications for CA1 vulnerability with aging. Cell Death Differ. 2009;16(3):439–48.Google Scholar
McEwen, BS, Morrison, JH. The brain on stress: vulnerability and plasticity of the prefrontal cortex over the life course. Neuron. 2013;79(1):1629.CrossRefGoogle ScholarPubMed
Wang, X, Michaelis, EK. Selective neuronal vulnerability to oxidative stress in the brain. Front Aging Neurosci. 2010;2:12.Google ScholarPubMed
Abd El Mohsen, MM, Iravani, MM, Spencer, JP, Rose, S, Fahim, AT, Motawi, TM, et al. Age-associated changes in protein oxidation and proteasome activities in rat brain: modulation by antioxidants. Biochem Biophys Res Commun. 2005;336(2):386–91.Google Scholar
Dominguez, M, de Oliveira, E, Odena, MA, Portero, M, Pamplona, R, Ferrer, I. Redox proteomic profiling of neuroketal-adducted proteins in human brain: regional vulnerability at middle age increases in the elderly. Free Radic Biol Med. 2016;95:115.Google Scholar
Horvath, S, Mah, V, Lu, AT, Woo, JS, Choi, OW, Jasinska, AJ, et al. The cerebellum ages slowly according to the epigenetic clock. Aging (Albany NY). 2015;7(5):294306.Google Scholar
Kumar, A, Gibbs, JR, Beilina, A, Dillman, A, Kumaran, R, Trabzuni, D, et al. Age-associated changes in gene expression in human brain and isolated neurons. Neurobiol Aging. 2013;34(4):1199–209.Google Scholar
Ianov, L, De Both, M, Chawla, MK, Rani, A, Kennedy, AJ, Piras, I, et al. Hippocampal transcriptomic profiles: subfield vulnerability to age and cognitive impairment. Front Aging Neurosci. 2017;9:383.Google Scholar
Foster, TC. Biological markers of age-related memory deficits: treatment of senescent physiology. CNS Drugs. 2006;20(2):153–66.Google Scholar
Febo, M, Foster, TC. Preclinical magnetic resonance imaging and spectroscopy studies of memory, aging, and cognitive decline. Front Aging Neurosci. 2016;8:158.Google Scholar
Goh, JO, An, Y, Resnick, SM. Differential trajectories of age-related changes in components of executive and memory processes. Psychol Aging. 2012;27(3):707–19.Google Scholar
McAvinue, LP, Habekost, T, Johnson, KA, Kyllingsbaek, S, Vangkilde, S, Bundesen, C, et al. Sustained attention, attentional selectivity, and attentional capacity across the lifespan. Atten Percept Psychophys. 2012;74(8):1570–82.Google Scholar
Guidi, M, Kumar, A, Foster, TC. Impaired attention and synaptic senescence of the prefrontal cortex involves redox regulation of NMDA receptors. J Neurosci. 2015;35(9):3966–77.Google Scholar
Jones, DN, Barnes, JC, Kirkby, DL, Higgins, GA. Age-associated impairments in a test of attention: evidence for involvement of cholinergic systems. J Neurosci. 1995;15(11):7282–92.Google Scholar
Fortenbaugh, FC, DeGutis, J, Germine, L, Wilmer, JB, Grosso, M, Russo, K, et al. Sustained attention across the life span in a sample of 10,000: dissociating ability and strategy. Psychol Sci. 2015;26(9):1497–510.Google Scholar
Bimonte, HA, Nelson, ME, Granholm, AC. Age-related deficits as working memory load increases: relationships with growth factors. Neurobiol Aging. 2003;24(1):3748.Google Scholar
Bopp, KL, Verhaeghen, P. Aging and verbal memory span: a meta-analysis. J Gerontol B Psychol Sci Soc Sci. 2005;60(5):P223–33.Google Scholar
Brockmole, JR, Logie, RH. Age-related change in visual working memory: a study of 55,753 participants aged 8–75. Front Psychol. 2013;4:12.Google Scholar
Dellu-Hagedorn, F, Trunet, S, Simon, H. Impulsivity in youth predicts early age-related cognitive deficits in rats. Neurobiol Aging. 2004;25(4):525–37.Google Scholar
Moss, MB, Killiany, RJ, Lai, ZC, Rosene, DL, Herndon, JG. Recognition memory span in rhesus monkeys of advanced age. Neurobiol Aging. 1997;18(1):1319.Google Scholar
Tapp, PD, Siwak, CT, Estrada, J, Holowachuk, D, Milgram, NW. Effects of age on measures of complex working memory span in the beagle dog (Canis familiaris) using two versions of a spatial list learning paradigm. Learn Mem. 2003;10(2):148–60.Google Scholar
Robbins, TW, James, M, Owen, AM, Sahakian, BJ, Lawrence, AD, McInnes, L, et al. A study of performance on tests from the CANTAB battery sensitive to frontal lobe dysfunction in a large sample of normal volunteers: implications for theories of executive functioning and cognitive aging. Cambridge Neuropsychological Test Automated Battery. J Int Neuropsychol Soc. 1998;4(5):474–90.Google Scholar
Rhodes, MG. Age-related differences in performance on the Wisconsin card sorting test: a meta-analytic review. Psychology Aging. 2004;19(3):482–94.Google Scholar
Fisk, JE, Sharp, CA. Age-related impairment in executive functioning: updating, inhibition, shifting, and access. J Clin Exp Neuropsychol. 2004;26(7):874–90.Google Scholar
Ianov, L, Rani, A, Beas, BS, Kumar, A, Foster, TC. Transcription profile of aging and cognition-related genes in the medial prefrontal cortex. Front Aging Neurosci. 2016;8:113.Google Scholar
Small, GW. What we need to know about age related memory loss. BMJ. 2002;324(7352):1502–5.Google Scholar
Cansino, S. Episodic memory decay along the adult lifespan: a review of behavioral and neurophysiological evidence. Int J Psychophysiol. 2009;71(1):64–9.Google Scholar
Uttl, B, Graf, P. Episodic spatial memory in adulthood. Psychol Aging. 1993;8(2):257–73.CrossRefGoogle ScholarPubMed
Nyberg, L, Lovden, M, Riklund, K, Lindenberger, U, Backman, L. Memory aging and brain maintenance. Trends Cogn Sci. 2012;16(5):292305.CrossRefGoogle ScholarPubMed
Foster, TC. Dissecting the age-related decline on spatial learning and memory tasks in rodent models: N-methyl-D-aspartate receptors and voltage-dependent Ca2+ channels in senescent synaptic plasticity. Prog Neurobiol. 2012;96(3):283303.CrossRefGoogle ScholarPubMed
Khachaturian, ZS. Hypothesis on the regulation of cytosol calcium concentration and the aging brain. Neurobiol Aging. 1987;8(4):345–6.CrossRefGoogle ScholarPubMed
Michaelis, ML, Johe, K, Kitos, TE. Age-dependent alterations in synaptic membrane systems for Ca2+ regulation. Mech Ageing Dev. 1984;25(1–2):215–25.Google Scholar
Landfield, PW, Pitler, TA. Prolonged Ca2+-dependent afterhyperpolarizations in hippocampal neurons of aged rats. Science. 1984;226(4678):1089–92.Google Scholar
Rapp, PR, Gallagher, M. Preserved neuron number in the hippocampus of aged rats with spatial learning deficits. Proc Natl Acad Sci USA. 1996;93(18):9926–30.Google Scholar
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):769–72.Google Scholar
Barnes, CA, McNaughton, BL. An age comparison of the rates of acquisition and forgetting of spatial information in relation to long-term enhancement of hippocampal synapses. Behav Neurosci. 1985;99(6):1040–8.Google Scholar
Foster, TC, Kumar, A. Susceptibility to induction of long-term depression is associated with impaired memory in aged Fischer 344 rats. Neurobiol Learn Mem. 2007;87(4):522–35.CrossRefGoogle ScholarPubMed
Norris, CM, Korol, DL, Foster, TC. Increased susceptibility to induction of long-term depression and long-term potentiation reversal during aging. J Neurosci. 1996;16(17):5382–92.Google Scholar
Kumar, A, Foster, TC. Linking redox regulation of NMDAR synaptic function to cognitive decline during aging. J Neurosci. 2013;33(40):15710–15.Google Scholar
Elman, JA, Oh, H, Madison, CM, Baker, SL, Vogel, JW, Marks, SM, et al. Neural compensation in older people with brain amyloid-beta deposition. Nat Neurosci. 2014;17(10):1316–18.CrossRefGoogle ScholarPubMed
O’Brien, JL, O’Keefe, KM, LaViolette, PS, DeLuca, AN, Blacker, D, Dickerson, BC, et al. Longitudinal fMRI in elderly reveals loss of hippocampal activation with clinical decline. Neurology. 2010;74(24):1969–76.Google Scholar
Foster, TC. Calcium homeostasis and modulation of synaptic plasticity in the aged brain. Aging Cell. 2007;6(3):319–25.CrossRefGoogle ScholarPubMed
Bodhinathan, K, Kumar, A, Foster, TC. Intracellular redox state alters NMDA receptor response during aging through Ca2+/calmodulin-dependent protein kinase II. J Neurosci. 2010;30(5):1914–24.Google Scholar
Foster, TC, Norris, CM. Age-associated changes in Ca(2+)-dependent processes: relation to hippocampal synaptic plasticity. Hippocampus. 1997;7(6):602–12.Google Scholar
Kumar, A, Foster, TC. Enhanced long-term potentiation during aging is masked by processes involving intracellular calcium stores. J Neurophysiol. 2004;91(6):2437–44.Google Scholar
Bodhinathan, K, Kumar, A, Foster, TC. Redox sensitive calcium stores underlie enhanced after hyperpolarization of aged neurons: role for ryanodine receptor mediated calcium signaling. J Neurophysiol. 2010;104(5):2586–93.Google Scholar
Kumar, A, Foster, TC. Intracellular calcium stores contribute to increased susceptibility to LTD induction during aging. Brain Res. 2005;1031(1):125–8.Google Scholar
Homayoun, H, Moghaddam, B. NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J Neurosci. 2007;27(43):11496–500.Google Scholar
Porges, EC, Woods, AJ, Edden, RA, Puts, NA, Harris, AD, Chen, H, et al. Frontal gamma-aminobutyric acid concentrations are associated with cognitive performance in older adults. Biol Psychiatry Cogn Neurosci Neuroimaging. 2017;2(1):3844.Google ScholarPubMed
Morgan, CJ, Curran, HV. Acute and chronic effects of ketamine upon human memory: a review. Psychopharmacology (Berl). 2006;188(4):408–24.Google Scholar
Forette, F, Seux, ML, Staessen, JA, Thijs, L, Babarskiene, MR, Babeanu, S, et al. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med. 2002;162(18):2046–52.Google Scholar
Lovell, MA, Abner, E, Kryscio, R, Xu, L, Fister, SX, Lynn, BC. Calcium channel blockers, progression to dementia, and effects on amyloid beta peptide production. Oxid Med Cell Longev. 2015;2015:787805.Google Scholar
Trompet, S, Westendorp, RG, Kamper, AM, de Craen, AJ. Use of calcium antagonists and cognitive decline in old age. The Leiden 85-plus study. Neurobiol Aging. 2008;29(2):306–8.Google Scholar
Barnes, CA. Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comp Physiol Psychol. 1979;93(1):74104.Google Scholar
Daselaar, SM, Iyengar, V, Davis, SW, Eklund, K, Hayes, SM, Cabeza, RE. Less wiring, more firing: low-performing older adults compensate for impaired white matter with greater neural activity. Cereb Cortex. 2015;25(4):983–90.Google Scholar
Kumar, A, Foster, TC. Neurophysiology of old neurons and synapses. In: Riddle, DR, editor. Brain Aging: Models, Methods, and Mechanisms. Frontiers in Neuroscience. Boca Raton, FL, 2007.Google Scholar
Neuman, KM, Molina-Campos, E, Musial, TF, Price, AL, Oh, KJ, Wolke, ML, et al. Evidence for Alzheimer’s disease-linked synapse loss and compensation in mouse and human hippocampal CA1 pyramidal neurons. Brain Struct Funct. 2015;220(6):3143–65.Google Scholar
Mormino, EC, Brandel, MG, Madison, CM, Marks, S, Baker, SL, Jagust, WJ. Aβ deposition in aging is associated with increases in brain activation during successful memory encoding. Cereb Cortex. 2012;22(8):1813–23.Google Scholar
Kennedy, KM, Rodrigue, KM, Bischof, GN, Hebrank, AC, Reuter-Lorenz, PA, Park, DC. Age trajectories of functional activation under conditions of low and high processing demands: an adult lifespan fMRI study of the aging brain. Neuroimage. 2015;104:2134.Google Scholar
Reuter-Lorenz, PA, Park, DC. Human neuroscience and the aging mind: a new look at old problems. J Gerontol B Psychol Sci Soc Sci. 2010;65(4):405–15.Google Scholar
Davis, SW, Dennis, NA, Daselaar, SM, Fleck, MS, Cabeza, R. Que PASA? The posterior-anterior shift in aging. Cereb Cortex. 2008;18(5):1201–9.Google Scholar
Oberman, L, Pascual-Leone, A. Changes in plasticity across the lifespan: cause of disease and target for intervention. Prog Brain Res. 2013;207:91120.Google Scholar
Kumar, A, Yegla, B, Foster, TC. Redox signaling in neurotransmission and cognition during aging. Antioxid Redox Signal. 2018;28:17241745.Google Scholar
Harman, D. Aging and oxidative stress. J Int Fed Clin Chem. 1998;10(1):24–7.Google Scholar
Lee, WH, Kumar, A, Rani, A, Foster, TC. Role of antioxidant enzymes in redox regulation of N-methyl-D-aspartate receptor function and memory in middle-aged rats. Neurobiol Aging. 2014;35(6):1459–68.Google Scholar
Lee, WH, Kumar, A, Rani, A, Herrera, J, Xu, J, Someya, S, et al. Influence of viral vector-mediated delivery of superoxide dismutase and catalase to the hippocampus on spatial learning and memory during aging. Antioxid Redox Signal. 2012;16(4):339–50.Google Scholar
Streit, WJ, Xue, QS, Tischer, J, Bechmann, I. Microglial pathology. Acta Neuropathol Commun. 2014;2:142.Google Scholar
Rafnsson, SB, Deary, IJ, Smith, FB, Whiteman, MC, Rumley, A, Lowe, GD, et al. Cognitive decline and markers of inflammation and hemostasis: the Edinburgh Artery Study. J Am Geriatr Soc. 2007;55(5):700–7.Google Scholar
Scheinert, RB, Asokan, A, Rani, A, Kumar, A, Foster, TC, Ormerod, BK. Some hormone, cytokine and chemokine levels that change across lifespan vary by cognitive status in male Fischer 344 rats. Brain Behav Immun. 2015;49:216–32.Google Scholar
Bean, LA, Ianov, L, Foster, TC. Estrogen receptors, the hippocampus, and memory. Neuroscientist. 2014;20(5):534–45.Google Scholar
Foster, TC. Interaction of rapid signal transduction cascades and gene expression in mediating estrogen effects on memory over the life span. Front Neuroendocrinol. 2005;26(2):5164.Google Scholar
Bean, LA, Kumar, A, Rani, A, Guidi, M, Rosario, AM, Cruz, PE, et al. Re-opening the critical window for estrogen therapy. J Neurosci. 2015;35(49):16077–93.Google Scholar
Kumar, A, Foster, TC. 17beta-estradiol benzoate decreases the AHP amplitude in CA1 pyramidal neurons. J Neurophysiol. 2002;88(2):621–6.Google Scholar
Foster, TC, Sharrow, KM, Kumar, A, Masse, J. Interaction of age and chronic estradiol replacement on memory and markers of brain aging. Neurobiol Aging. 2003;24(6):839–52.Google Scholar
Vedder, LC, Bredemann, TM, McMahon, LL. Estradiol replacement extends the window of opportunity for hippocampal function. Neurobiol Aging. 2014;35(10):2183–92.Google Scholar
Lopez-Grueso, R, Gambini, J, Abdelaziz, KM, Monleon, D, Diaz, A, El Alami, M, et al. Early, but not late onset estrogen replacement therapy prevents oxidative stress and metabolic alterations caused by ovariectomy. Antioxid Redox Signal. 2014;20(2):236–46.Google Scholar
Moorthy, K, Sharma, D, Basir, SF, Baquer, NZ. Administration of estradiol and progesterone modulate the activities of antioxidant enzyme and aminotransferases in naturally menopausal rats. Exp Gerontol. 2005;40(4):295302.Google Scholar
McCarrey, AC, Resnick, SM. Postmenopausal hormone therapy and cognition. Horm Behav. 2015;74:167–72.Google Scholar
Aenlle, KK, Foster, TC. Aging alters the expression of genes for neuroprotection and synaptic function following acute estradiol treatment. Hippocampus. 2010;20(9):1047–60.Google Scholar
Blalock, EM, Chen, KC, Sharrow, K, Herman, JP, Porter, NM, Foster, TC, et al. Gene microarrays in hippocampal aging: statistical profiling identifies novel processes correlated with cognitive impairment. J Neurosci. 2003;23(9):3807–19.Google Scholar
Prolla, TA. DNA microarray analysis of the aging brain. Chem Senses. 2002;27(3):299306.Google Scholar
VanGuilder, HD, Bixler, GV, Brucklacher, RM, Farley, JA, Yan, H, Warrington, JP, et al. Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment. J Neuroinflammation. 2011;8:138.Google Scholar
Fraga, MF, Ballestar, E, Paz, MF, Ropero, S, Setien, F, Ballestar, ML, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA. 2005;102(30):10604–9.Google Scholar
Starnawska, A, Tan, Q, McGue, M, Mors, O, Borglum, AD, Christensen, K, et al. Epigenome-wide association study of cognitive functioning in middle-aged monozygotic twins. Front Aging Neurosci. 2017;9:413.Google Scholar
Leu, YW, Yan, PS, Fan, M, Jin, VX, Liu, JC, Curran, EM, et al. Loss of estrogen receptor signaling triggers epigenetic silencing of downstream targets in breast cancer. Cancer Res. 2004;64(22):8184–92.CrossRefGoogle ScholarPubMed
Moreno-Piovano, GS, Varayoud, J, Luque, EH, Ramos, JG. Long-term ovariectomy increases BDNF gene methylation status in mouse hippocampus. J Steroid Biochem Mol Biol. 2014;144 Pt B:243–52.Google Scholar
Carter, SD, Mifsud, KR, Reul, JM. Distinct epigenetic and gene expression changes in rat hippocampal neurons after Morris water maze training. Front Behav Neurosci. 2015;9:156.CrossRefGoogle ScholarPubMed
Han, Y, Han, D, Yan, Z, Boyd-Kirkup, JD, Green, CD, Khaitovich, P, et al. Stress-associated H3K4 methylation accumulates during postnatal development and aging of rhesus macaque brain. Aging Cell. 2012;11(6):1055–64.Google Scholar
Kenworthy, CA, Sengupta, A, Luz, SM, Ver Hoeve, ES, Meda, K, Bhatnagar, S, et al. Social defeat induces changes in histone acetylation and expression of histone modifying enzymes in the ventral hippocampus, prefrontal cortex, and dorsal raphe nucleus. Neuroscience. 2014;264:8898.Google Scholar
Oh, JE, Chambwe, N, Klein, S, Gal, J, Andrews, S, Gleason, G, et al. Differential gene body methylation and reduced expression of cell adhesion and neurotransmitter receptor genes in adverse maternal environment. Transl Psychiatry. 2013;3:e218.Google Scholar
Ianov, L, Riva, A, Kumar, A, Foster, TC. DNA methylation of synaptic genes in the prefrontal cortex is associated with aging and age-related cognitive impairment. Front Aging Neurosci. 2017;9:249.Google Scholar
Foster, TC, Sharrow, KM, Masse, JR, Norris, CM, Kumar, A. Calcineurin links Ca2+ dysregulation with brain aging. J Neurosci. 2001;21(11):4066–73.Google Scholar
Penner, MR, Parrish, RR, Hoang, LT, Roth, TL, Lubin, FD, Barnes, CA. Age-related changes in Egr1 transcription and DNA methylation within the hippocampus. Hippocampus. 2016;26(8):1008–20.Google Scholar
Penner, MR, Roth, TL, Chawla, MK, Hoang, LT, Roth, ED, Lubin, FD, et al. Age-related changes in Arc transcription and DNA methylation within the hippocampus. Neurobiol Aging. 2011;32(12):2198–210.Google Scholar
Grinan-Ferre, C, Puigoriol-Illamola, D, Palomera-Avalos, V, Perez-Caceres, D, Companys-Alemany, J, Camins, A, et al. Environmental enrichment modified epigenetic mechanisms in SAMP8 mouse hippocampus by reducing oxidative stress and inflammaging and achieving neuroprotection. Front Aging Neurosci. 2016;8:241.Google Scholar
Weaver, IC, Champagne, FA, Brown, SE, Dymov, S, Sharma, S, Meaney, MJ, et al. Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life. J Neurosci. 2005;25(47):11045–54.Google Scholar
Zhang, TY, Keown, CL, Wen, X, Li, J, Vousden, DA, Anacker, C, et al. Environmental enrichment increases transcriptional and epigenetic differentiation between mouse dorsal and ventral dentate gyrus. Nat Commun. 2018;9(1):298.Google Scholar
Cechinel, LR, Basso, CG, Bertoldi, K, Schallenberger, B, de Meireles, LC, Siqueira, IR. Treadmill exercise induces age and protocol-dependent epigenetic changes in prefrontal cortex of Wistar rats. Behav Brain Res. 2016;313:82–7.CrossRefGoogle ScholarPubMed
Cosin-Tomas, M, Alvarez-Lopez, MJ, Sanchez-Roige, S, Lalanza, JF, Bayod, S, Sanfeliu, C, et al. Epigenetic alterations in hippocampus of SAMP8 senescent mice and modulation by voluntary physical exercise. Front Aging Neurosci. 2014;6:51.Google Scholar
Feil, R. Environmental and nutritional effects on the epigenetic regulation of genes. Mutat Res. 2006;600(1–2):4657.Google Scholar
Rani, A, O’Shea, A, Ianov, L, Cohen, RA, Woods, AJ, Foster, TC. miRNA in circulating microvesicles as biomarkers for age-related cognitive decline. Front Aging Neurosci. 2017;9:323.Google Scholar
Freedman, JE, Gerstein, M, Mick, E, Rozowsky, J, Levy, D, Kitchen, R, et al. Diverse human extracellular RNAs are widely detected in human plasma. Nat Commun. 2016;7:11106.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×