Abstract
Ageing reduces the functional capacity of all organs, so does that of the nervous system; the latter is evident in the reduction of cognitive abilities, learning and memory. While the exact mechanisms of ageing of the nervous system remain elusive, it is without doubt that morpho-functional changes in a variety of neuroglial cells contribute to this process. The age-dependent changes in neuroglia are characterised by a progressive loss of function. This reduces glial ability to homeostatically nurture, protect and regenerate the nervous tissue. Such neuroglial paralysis also facilitates neurodegenerative processes. Ageing of neuroglia is variable and can be affected by environmental factors and comorbidities.
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Bartzokis G, Beckson M, Lu PH, Nuechterlein KH, Edwards N, Mintz J (2001) Age-related changes in frontal and temporal lobe volumes in men: a magnetic resonance imaging study. Arch Gen Psychiatry 58:461–465
Bisht K, Sharma KP, Lecours C, Sanchez MG, El Hajj H, Milior G, Olmos-Alonso A, Gomez-Nicola D, Luheshi G, Vallieres L, Branchi I, Maggi L, Limatola C, Butovsky O, Tremblay ME (2016) Dark microglia: a new phenotype predominantly associated with pathological states. Glia 64:826–839
Black S, Gao F, Bilbao J (2009) Understanding white matter disease: imaging-pathological correlations in vascular cognitive impairment. Stroke 40:S48–52
Boisvert MM, Erikson GA, Shokhirev MN, Allen NJ (2018) The aging astrocyte transcriptome from multiple regions of the mouse brain. Cell Rep 22:269–285
Bolos M, Llorens-Martin M, Jurado-Arjona J, Hernandez F, Rabano A, Avila J (2016) Direct evidence of internalization of tau by microglia in vitro and in vivo. J Alzheimer’s Dis 50:77–87
Calhoun ME, Kurth D, Phinney AL, Long JM, Hengemihle J, Mouton PR, Ingram DK, Jucker M (1998) Hippocampal neuron and synaptophysin-positive bouton number in aging C57BL/6 mice. Neurobiol Aging 19:599–606
Cerbai F, Lana D, Nosi D, Petkova-Kirova P, Zecchi S, Brothers HM, Wenk GL, Giovannini MG (2012) The neuron-astrocyte-microglia triad in normal brain ageing and in a model of neuroinflammation in the rat hippocampus. PLoS ONE 7:e45250
Clarke LE, Liddelow SA, Chakraborty C, Munch AE, Heiman M, Barres BA (2018) Normal aging induces A1-like astrocyte reactivity. Proc Natl Acad Sci USA 115:E1896–E1905
Cruz NF, Ball KK, Dienel GA (2010) Astrocytic gap junctional communication is reduced in amyloid-beta-treated cultured astrocytes, but not in Alzheimer’s disease transgenic mice. ASN Neuro 2:e00041
David JP, Ghozali F, Fallet-Bianco C, Wattez A, Delaine S, Boniface B, Di Menza C, Delacourte A (1997) Glial reaction in the hippocampal formation is highly correlated with aging in human brain. Neurosci Lett 235:53–56
Davies DS, Ma J, Jegathees T, Goldsbury C (2017) Microglia show altered morphology and reduced arborization in human brain during aging and Alzheimer’s disease. Brain Pathol 27:795–808
Dickstein D, Kabaso D, Rocher A, Luebke J, Wearne S, Hof P (2006) Changes in the structural complexity of the aged brain. Aging Cell 6:275–284
Dimou L, Gallo V (2015) NG2-glia and their functions in the central nervous system. Glia 63:1429–1451
Diniz DG, Foro CA, Rego CM, Gloria DA, de Oliveira FR, Paes JM, de Sousa AA, Tokuhashi TP, Trindade LS, Turiel MC, Vasconcelos EG, Torres JB, Cunnigham C, Perry VH, Vasconcelos PF, Diniz CW (2010) Environmental impoverishment and aging alter object recognition, spatial learning, and dentate gyrus astrocytes. Eur J Neurosci 32:509–519
Douaud G, Groves AR, Tamnes CK, Westlye LT, Duff EP, Engvig A, Walhovd KB, James A, Gass A, Monsch AU, Matthews PM, Fjell AM, Smith SM, Johansen-Berg H (2014) A common brain network links development, aging, and vulnerability to disease. Proc Natl Acad Sci USA 111:17648–17653
Duarte JM, Do KQ, Gruetter R (2014) Longitudinal neurochemical modifications in the aging mouse brain measured in vivo by 1H magnetic resonance spectroscopy. Neurobiol Aging 35:1660–1668
Emir UE, Raatz S, McPherson S, Hodges JS, Torkelson C, Tawfik P, White T, Terpstra M (2011) Noninvasive quantification of ascorbate and glutathione concentration in the elderly human brain. NMR Biomed 24:888–894
Erickson CA, Barnes CA (2003) The neurobiology of memory changes in normal aging. Exp Gerontol 38:61–69
Fabricius K, Jacobsen JS, Pakkenberg B (2013) Effect of age on neocortical brain cells in 90+ year old human females—a cell counting study. Neurobiol Aging 34:91–99
Fabris N (1991) Neuroendocrine-immune interactions: a theoretical approach to aging. Arch Gerontol Geriatr 12:219–230
Franceschi C (2007) Inflammaging as a major characteristic of old people: can it be prevented or cured? Nutr Rev 65:S173–176
Garaschuk O, Verkhratsky A (2019) GABAergic astrocytes in Alzheimer’s disease. Aging (Albany NY) 11:1602–1604
Geinisman Y, Ganeshina O, Yoshida R, Berry RW, Disterhoft JF, Gallagher M (2004) Aging, spatial learning, and total synapse number in the rat CA1 stratum radiatum. Neurobiol Aging 25:407–416
Gomez-Gonzalo M, Martin-Fernandez M, Martinez-Murillo R, Mederos S, Hernandez-Vivanco A, Jamison S, Fernandez AP, Serrano J, Calero P, Futch HS, Corpas R, Sanfeliu C, Perea G, Araque A (2017) Neuron-astrocyte signaling is preserved in the aging brain. Glia 65:569–580
Griffin R, Nally R, Nolan Y, McCartney Y, Linden J, Lynch MA (2006) The age-related attenuation in long-term potentiation is associated with microglial activation. J Neurochem 99:1263–1272
Grosche A, Grosche J, Tackenberg M, Scheller D, Gerstner G, Gumprecht A, Pannicke T, Hirrlinger PG, Wilhelmsson U, Huttmann K, Hartig W, Steinhauser C, Pekny M, Reichenbach A (2013) Versatile and simple approach to determine astrocyte territories in mouse neocortex and hippocampus. PLoS ONE 8:e69143
Hardy RN, Simsek ZD, Curry B, Core SL, Beltz T, Xue B, Johnson AK, Thunhorst RL, Curtis KS (2018) Aging affects isoproterenol-induced water drinking, astrocyte density, and central neuronal activation in female Brown Norway rats. Physiol Behav 192:90–97
Harley CB, Vaziri H, Counter CM, Allsopp RC (1992) The telomere hypothesis of cellular aging. Exp Gerontol 27:375–382
Harman D (1965) The free radical theory of aging: effect of age on serum copper levels. J Gerontol 20:151–153
Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20:145–147
Harris JL, Choi IY, Brooks WM (2015) Probing astrocyte metabolism in vivo: proton magnetic resonance spectroscopy in the injured and aging brain. Front Aging Neurosci 7:202
Harris JL, Yeh HW, Swerdlow RH, Choi IY, Lee P, Brooks WM (2014) High-field proton magnetic resonance spectroscopy reveals metabolic effects of normal brain aging. Neurobiol Aging 35:1686–1694
Haug H, Eggers R (1991) Morphometry of the human cortex cerebri and corpus striatum during aging. Neurobiol Aging 12:336–338; discussion 352–335
Hayakawa N, Kato H, Araki T (2007) Age-related changes of astorocytes, oligodendrocytes and microglia in the mouse hippocampal CA1 sector. Mech Ageing Dev 128:311–316
Hedden T, Gabrieli JD (2004) Insights into the ageing mind: a view from cognitive neuroscience. Nat Rev Neurosci 5:87–96
Jessen NA, Munk AS, Lundgaard I, Nedergaard M (2015) The glymphatic system: a beginner’s guide. Neurochem Res 40:2583–2599
Jiang T, Cadenas E (2014) Astrocytic metabolic and inflammatory changes as a function of age. Aging Cell
Juurlink BH, Thorburne SK, Hertz L (1998) Peroxide-scavenging deficit underlies oligodendrocyte susceptibility to oxidative stress. Glia 22:371–378
Kanungo MS (1975) A model for ageing. J Theoret Biol 53:253–261
Khachaturian ZS (1987) Hypothesis on the regulation of cytosol calcium concentration and the aging brain. Neurobiol Aging 8:345–346
Kirischuk S, Parpura V, Verkhratsky A (2012) Sodium dynamics: another key to astroglial excitability? Trends Neurosci 35:497–506
Kress BT, Iliff JJ, Xia M, Wang M, Wei H, Zeppenfeld D, Xie L, Kang H, Xu Q, Liew J, Plog BA, Ding F, Deane R, Nedergaard M (2014) Impairment of paravascular clearance pathways in the aging brain. Ann Neurol
Krimer LS, Hyde TM, Herman MM, Saunders RC (1997) The entorhinal cortex: an examination of cyto- and myeloarchitectonic organization in humans. Cereb Cortex 7:722–731
Lalo U, Palygin O, North RA, Verkhratsky A, Pankratov Y (2011) Age-dependent remodelling of ionotropic signalling in cortical astroglia. Aging Cell 10:392–402
Landfield PW (1987) ‘Increased calcium-current’ hypothesis of brain aging. Neurobiol Aging 8:346–347
Lee DC, Ruiz CR, Lebson L, Selenica ML, Rizer J, Hunt JB Jr, Rojiani R, Reid P, Kammath S, Nash K, Dickey CA, Gordon M, Morgan D (2013) Aging enhances classical activation but mitigates alternative activation in the central nervous system. Neurobiol Aging 34:1610–1620
Logan JM, Sanders AL, Snyder AZ, Morris JC, Buckner RL (2002) Under-recruitment and nonselective recruitment: dissociable neural mechanisms associated with aging. Neuron 33:827–840
Lopez-Otin C, Galluzzi L, Freije JMP, Madeo F, Kroemer G (2016) Metabolic control of longevity. Cell 166:802–821
Lynch AM, Murphy KJ, Deighan BF, O’Reilly JA, Gun’ko YK, Cowley TR, Gonzalez-Reyes RE, Lynch MA (2010) The impact of glial activation in the aging brain. Aging Dis 1:262–278
Maher P (2005) The effects of stress and aging on glutathione metabolism. Ageing Res Rev 4:288–314
Matute C, Alberdi E, Domercq M, Sanchez-Gomez MV, Perez-Samartin A, Rodriguez-Antiguedad A, Perez-Cerda F (2007) Excitotoxic damage to white matter. J Anat 210:693–702
Medvedev ZA (1990) An attempt at a rational classification of theories of ageing. Biol Rev Camb Philos Soc 65:375–398
Micu I, Jiang Q, Coderre E, Ridsdale A, Zhang L, Woulfe J, Yin X, Trapp BD, McRory JE, Rehak R, Zamponi GW, Wang W, Stys PK (2006) NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia. Nature 439:988–992
Ming GL, Song H (2011) Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70:687–702
Nichols NR, Day JR, Laping NJ, Johnson SA, Finch CE (1993) GFAP mRNA increases with age in rat and human brain. Neurobiol Aging 14:421–429
Nicholson DA, Yoshida R, Berry RW, Gallagher M, Geinisman Y (2004) Reduction in size of perforated postsynaptic densities in hippocampal axospinous synapses and age-related spatial learning impairments. J Neurosci 24:7648–7653
Ogura K, Ogawa M, Yoshida M (1994) Effects of ageing on microglia in the normal rat brain: immunohistochemical observations. NeuroReport 5:1224–1226
Orre M, Kamphuis W, Osborn LM, Jansen AH, Kooijman L, Bossers K, Hol EM (2014) Isolation of glia from Alzheimer’s mice reveals inflammation and dysfunction. Neurobiol Aging
Pelvig DP, Pakkenberg H, Stark AK, Pakkenberg B (2008) Neocortical glial cell numbers in human brains. Neurobiol Aging 29:1754–1762
Perry VH, Matyszak MK, Fearn S (1993) Altered antigen expression of microglia in the aged rodent CNS. Glia 7:60–67
Peters A, Josephson K, Vincent SL (1991) Effects of aging on the neuroglial cells and pericytes within area 17 of the rhesus monkey cerebral cortex. Anat Rec 229:384–398
Peters A, Sethares C (2004) Oligodendrocytes, their progenitors and other neuroglial cells in the aging primate cerebral cortex. Cereb Cortex 14:995–1007
Peters O, Schipke CG, Philipps A, Haas B, Pannasch U, Wang LP, Benedetti B, Kingston AE, Kettenmann H (2009) Astrocyte function is modified by Alzheimer’s disease-like pathology in aged mice. J Alzheimers Dis 18:177–189
Potokar M, Stenovec M, Jorgacevski J, Holen T, Kreft M, Ottersen OP, Zorec R (2013) Regulation of AQP4 surface expression via vesicle mobility in astrocytes. Glia 61:917–928
Provenzano FA, Muraskin J, Tosto G, Narkhede A, Wasserman BT, Griffith EY, Guzman VA, Meier IB, Zimmerman ME, Brickman AM, Alzheimer’s Disease Neuroimaging I (2013) White matter hyperintensities and cerebral amyloidosis: necessary and sufficient for clinical expression of Alzheimer disease? JAMA Neurol 70, 455–461
Raz N, Lindenberger U, Rodrigue KM, Kennedy KM, Head D, Williamson A, Dahle C, Gerstorf D, Acker JD (2005) Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cereb Cortex 15:1676–1689
Rodriguez-Callejas JD, Fuchs E, Perez-Cruz C (2016) Evidence of Tau hyperphosphorylation and dystrophic microglia in the common marmoset. Front Aging Neurosci 8:315
Rodriguez JJ, Terzieva S, Olabarria M, Lanza RG, Verkhratsky A (2013) Enriched environment and physical activity reverse astrogliodegeneration in the hippocampus of AD transgenic mice. Cell Death Dis 4:e678
Rodriguez JJ, Yeh CY, Terzieva S, Olabarria M, Kulijewicz-Nawrot M, Verkhratsky A (2014) Complex and region-specific changes in astroglial markers in the aging brain. Neurobiol Aging 35:15–23
Rose CF, Verkhratsky A, Parpura V (2013) Astrocyte glutamine synthetase: pivotal in health and disease. Biochem Soc Trans 41:1518–1524
Rose CR, Verkhratsky A (2016) Principles of sodium homeostasis and sodium signalling in astroglia. Glia
Ruzicka V (1924) Beitrage zum Stadium der Protoplasmahysteretischen Vorgange (Zur Kausalitat der Alterns). Archiv fur mikroskopische Anatomie und Entwicklungsmechanik 101:459–482
Ruzicka V (1926) Altern und Verjungung won Standpunkt der allegemeinen Biologie. Praha, Praha
Salter MG, Fern R (2005) NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury. Nature 438:1167–1171
Sampedro-Piquero P, De Bartolo P, Petrosini L, Zancada-Menendez C, Arias JL, Begega A (2014) Astrocytic plasticity as a possible mediator of the cognitive improvements after environmental enrichment in aged rats. Neurobiol Learn Mem 114:16–25
Schoenemann PT, Sheehan MJ, Glotzer LD (2005) Prefrontal white matter volume is disproportionately larger in humans than in other primates. Nat Neurosci 8:242–252
Sharaf A, Krieglstein K, Spittau B (2013) Distribution of microglia in the postnatal murine nigrostriatal system. Cell Tissue Res 351:373–382
Sheffield LG, Berman NE (1998) Microglial expression of MHC class II increases in normal aging of nonhuman primates. Neurobiol Aging 19:47–55
Sierra A, Gottfried-Blackmore AC, McEwen BS, Bulloch K (2007) Microglia derived from aging mice exhibit an altered inflammatory profile. Glia 55:412–424
Smith TD, Adams MM, Gallagher M, Morrison JH, Rapp PR (2000) Circuit-specific alterations in hippocampal synaptophysin immunoreactivity predict spatial learning impairment in aged rats. J Neurosci 20:6587–6593
Soreq L, Consortium UKBE, North American Brain Expression C, Rose J, Soreq E, Hardy J, Trabzuni D, Cookson MR, Smith C, Ryten M, Patani R, Ule J (2017) Major shifts in glial regional identity are a transcriptional hallmark of human brain aging. Cell Rep 18:557–570
Stern Y (2009) Cognitive reserve. Neuropsychologia 47:2015–2028
Streit WJ, Braak H, Xue QS, Bechmann I (2009) Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer’s disease. Acta Neuropathol 118:475–485
Streit WJ, Sammons NW, Kuhns AJ, Sparks DL (2004) Dystrophic microglia in the aging human brain. Glia 45:208–212
Streit WJ, Xue QS, Tischer J, Bechmann I (2014) Microglial pathology. Acta Neuropathol Commun 2:142
Taylor RC (2016) Aging and the UPR(ER). Brain Res 1648:588–593
Thorburne SK, Juurlink BH (1996) Low glutathione and high iron govern the susceptibility of oligodendroglial precursors to oxidative stress. J Neurochem 67:1014–1022
Tischer J, Krueger M, Mueller W, Staszewski O, Prinz M, Streit WJ, Bechmann I (2016) Inhomogeneous distribution of Iba-1 characterizes microglial pathology in Alzheimer’s disease. Glia 64:1562–1572
Toescu EC, Verkhratsky A (2007) The importance of being subtle: small changes in calcium homeostasis control cognitive decline in normal aging. Aging Cell 6:267–273
Tse KH, Herrup K (2017) DNA damage in the oligodendrocyte lineage and its role in brain aging. Mech Ageing Dev 161:37–50
VanGuilder HD, Bixler GV, Brucklacher RM, Farley JA, Yan H, Warrington JP, Sonntag WE, Freeman WM (2011) Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment. J Neuroinflammation 8:138
Verkhratsky A, Kirchhoff F (2007) NMDA Receptors in glia. Neuroscientist 13:28–37
Verkhratsky A, Marutle A, Rodriguez-Arellano JJ, Nordberg A (2015) Glial asthenia and functional paralysis: a new perspective on neurodegeneration and Alzheimer’s disease. Neuroscientist 21:552–568
Verkhratsky A, Matteoli M, Parpura V, Mothet JP, Zorec R (2016) Astrocytes as secretory cells of the central nervous system: idiosyncrasies of vesicular secretion. EMBO J 35:239–257
Verkhratsky A, Nedergaard M (2018) Physiology of Astroglia. Physiol Rev 98:239–389
Verkhratsky A, Rodriguez JJ, Parpura V (2012) Calcium signalling in astroglia. Mol Cell Endocrinol 353:45–56
Verkhratsky A, Untiet V, Rose CR (2019) Ionic signalling in astroglia beyond calcium. J Physiol
Walhovd KB, Johansen-Berg H, Karadottir RT (2014) Unraveling the secrets of white matter—bridging the gap between cellular, animal and human imaging studies. Neuroscience 276C:2–13
Weismann A (1881) Ueber die Dauer des Lebens. Vortrag, in der 2. allgemeinen Sitzung d. 54. Versammlung Deutscher Naturforscher u. Aerzte in Salzburg, am 21, Sept 1881
West MJ (1993) Regionally specific loss of neurons in the aging human hippocampus. Neurobiol Aging 14:287–293
Young VG, Halliday GM, Kril JJ (2008) Neuropathologic correlates of white matter hyperintensities. Neurology 71:804–811
Zhu X, Hill RA, Dietrich D, Komitova M, Suzuki R, Nishiyama A (2011) Age-dependent fate and lineage restriction of single NG2 cells. Development 138:745–753
Zorec R, Parpura V, Verkhratsky A (2018) Preventing neurodegeneration by adrenergic astroglial excitation. FEBS J
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VP’s work is supported by a grant from the National Institute of General Medical Sciences of the National Institutes of Health (R01GM123971). VP is an Honorary Professor at University of Rijeka, Croatia.
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Verkhratsky, A., Zorec, R., Rodriguez-Arellano, J.J., Parpura, V. (2019). Neuroglia in Ageing. In: Verkhratsky, A., Ho, M., Zorec, R., Parpura, V. (eds) Neuroglia in Neurodegenerative Diseases. Advances in Experimental Medicine and Biology, vol 1175. Springer, Singapore. https://doi.org/10.1007/978-981-13-9913-8_8
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