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Brain aging research

  • David R Riddle (a1) (a2) (a3) and Matthew K Schindler (a2)
  • DOI: http://dx.doi.org/10.1017/S0959259808002530
  • Published online: 01 November 2007
Abstract

The last three decades produced a striking increase in investigations of the neurobiological basis of brain aging and aging-related changes in neural and cognitive function. Experimental and clinical studies of aging have become more valuable as the population, at least in industrialized countries, has become ‘greyer’. The increase in adult life expectancy that occurred in the twentieth century produced the motivation and necessity to invest resources in increasing ‘health span’ as well as lifespan, in order to maximize quality of life and minimize the financial and social burdens associated with disability in the later years of life. Specific interest in the aging nervous system is driven by recognition that increased longevity has little appeal for most people unless it is accompanied by maintenance of cognitive abilities. Indeed, surveys of older individuals routinely show that loss of mental capacity is among their greatest fear. In recent years, neuroscientists and gerontologists, with a variety of training and experimental approaches, have applied increasingly powerful quantitative methods to investigate why neural function declines with age. New animal model systems have been developed and old ones have become better characterized and standardized. The necessary and important descriptive studies that dominated the field in earlier years are increasingly supplemented by more hypothesis-driven research, resulting in sophisticated investigations and models of the mechanisms of brain aging. This review provides a selective overview of recent and current research on brain aging. The focus throughout will be on normal brain aging and the moderate cognitive changes that often accompany it, not on aging-related neurodegenerative diseases that result in dementia. To provide a context for studies of neurobiological changes in the aging brain, a brief overview of the types of cognitive changes that are commonly seen in aging humans is first provided. The remainder of the review focuses on animal studies that are progressively overcoming the unique challenges of aging research to reveal the neurobiological mechanisms of aging-related cognitive dysfunction, and suggest new targets for therapies to prevent or ameliorate cognitive decline.

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Corresponding author
Address for correspondence: DR Riddle, Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1010, USA.
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1EL Gliskey . Changes in cognitive function in human aging. In: DR Riddle ed. Brain aging: models, methods and mechanisms. Boca Raton: CRC Press, 2007: 320.

2P Verhaeghen , J Cerella . Aging, executive control, and attention: a review of meta-analyses. Neurosci Biobehav Rev 2002; 26: 849–57.

3WJ Thornton , N Raz . Aging and the role of working memory resources in visuospatial attention. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2006; 13: 3661.

5P Verhaeghen , C Basak . Ageing and switching of the focus of attention in working memory: results from a modified N-back task. Q J Exp Psychol A 2005; 58: 134–54.

6MJ Hogan , CA Kelly , FI Craik . The effects of attention-switching on encoding and retrieval of words in younger and older adults. Exp Aging Res 2006; 32: 153–83.

7CH Hillman , KI Erickson , AF Kramer . Be smart, exercise your heart. Exercise effects on brain cognition. Nature Rev Neurosci 2008; 9: 5865

9MA Luszcz , J Bryan . Toward understanding age-related memory-loss in late adulthood. Gerontology 1999; 45: 29.

10CL Grady , FI Craik . Changes in memory processing with age. Curr Opin Neurobiol 2000; 10: 224–31.

12RL. Buckner Memory and executive function in aging and AD: multiple factors that cause decline and reserve factors that compensate. Neuron 2004; 44: 195208.

13SN Burke , CA Barnes . Neural plasticity in the ageing brain. Nat Rev Neurosci 2006; 7: 3040.

14J Tanji , E Hoshi . Role of the lateral prefrontal cortex in executive behavioral control. Physiol Rev 2008; 88: 3757.

15RL West . An application of prefrontal cortex function theory to cognitive aging. Psychol Bull 1996; 120: 272–92.

17T Hedden . Imaging cognition in the aging human brain. In: DR Riddle ed. Brain aging: models, methods and mechanisms. Boca Raton: CRC Press, 2007: 251–78.

18N Raz , KM Rodrigue , EM Haacke . Brain aging and its modifiers: insights from in vivo neuromorphometry and susceptibility weighted imaging. Ann N Y Acad Sci 2007; 1097: 8493.

19D Prvulovic , V Van de Ven , AT Sack , K Maurer , DE Linden . Functional activation imaging in aging and dementia. Psychiatry Res 2005 Nov 30; 140: 97113.

20MN Rajah , M D'Esposito . Region-specific changes in prefrontal function with age: a review of PET and fMRI studies on working and episodic memory. Brain 2005; 128 (Pt 9): 1964–83.

21RM Kessler . Imaging methods for evaluating brain function in man. Neurobiol Aging 2003; 24 (suppl 1): 2135; discussion S3739.

22CC Meltzer , JT Becker , JC Price , E Moses-Kolko . Positron emission tomography imaging of the aging brain. Neuroimaging Clin N Am 2003; 13: 759–67.

23RA Charlton , DJ McIntyre , FA Howe , RG Morris , HS Markus . The relationship between white matter brain metabolites and cognition in normal aging: the GENIE study. Brain Res 2007; 1164: 108–16.

24DJ McIntyre , RA Charlton , HS Markus , FA Howe . Long and short echo-time proton magnetic resonance spectroscopic imaging of the healthy aging brain. J Magn Reson Imaging 2007; 26: 1596–606.

25JR Petrella , VS Mattay , PM Doraiswamy . Imaging genetics of brain longevity and mental wellness: the next frontier? Radiology 2008; 246: 2032.

27NL Nadon . Of mice and monkeys: National Institute on Aging resources supporting the use of animal models in biogerontology research. J Gerontol A Biol Sci Med Sci 2006; 61: 813–15.

28R Dias , TW Robbins , AC Roberts . Primate analogue of the Wisconsin Card Sorting Test: effects of excitotoxic lesions of the prefrontal cortex in the marmoset. Behav Neurosci 1996; 110: 872–86.

29R Dias , TW Robbins , AC Roberts . Dissociation in prefrontal cortex of affective and attentional shifts. Nature 1996; 380 (6569): 6972.

30JG Herndon , A Lacreuse . The Rhesus Monkey Model as a heuristic resource in cognitive aging research. In: JM Erwin , PR Hof ed. Aging in nonhuman primates. Interdiscipl Top Gerontol Basel. Karger, 2002; 31: 178195.

32Y Geinisman , O Ganeshina , R Yoshida , RW Berry , JF Disterhoft , M Gallagher . Aging, spatial learning, and total synapse number in the rat CA1 stratum radiatum. Neurobiol Aging 2004; 25: 407–16.

33DA Nicholson , R Yoshida , RW Berry , M Gallagher , Y Geinisman . Reduction in size of perforated postsynaptic densities in hippocampal axospinous synapses and age-related spatial learning impairments. J Neurosci 2004; 24: 7648–53.

35HK Lee , SS Min , M Gallagher , A Kirkwood . NMDA receptor-independent long-term depression correlates with successful aging in rats. Nat Neurosci 2005; 8: 1657–59.

37MD Barense , MT Fox , MG Baxter . Aged rats are impaired on an attentional set-shifting task sensitive to medial frontal cortex damage in young rats. Learn Mem 2002; 9: 191201.

38VJ Brown , EM Bowman . Rodent models of prefrontal cortical function. Trends Neurosci 2002; 25: 340–43.

39JK Andersen . Genetically engineered mice and their use in aging research. Mol Biotechnol 2001; 19: 4557.

40GM Martin . Genetic engineering of mice to test the oxidative damage theory of aging. Ann N Y Acad Sci. 2005; 1055: 2634.

41A Bartke . New findings in gene knockout, mutant and transgenic mice. Exp Gerontol 2008; 43: 1114.

42A Peters , JH Morrison , DL Rosene , BT Hyman . Feature article: are neurons lost from the primate cerebral cortex during normal aging? Cereb Cortex 1998; 8: 295–00.

43TL Jernigan , SL Archibald , C Fennema-Notestine Effects of age on tissues and regions of the cerebrum and cerebellum. Neurobiol Aging 2001; 22: 581–94.

44C Van Petten , E Plante , PS Davidson , TY Kuo , L Bajuscak , EL Glisky . Memory and executive function in older adults: relationships with temporal and prefrontal gray matter volumes and white matter hyperintensities. Neuropsychologia 2004; 42: 1313–35.

45JS Allen , J Bruss , CK Brown , H Damasio . Normal neuroanatomical variation due to age: the major lobes and a parcellation of the temporal region. Neurobiol Aging 2005; 26: 1245–60.

46MJ West . Regionally specific loss of neurons in the aging human hippocampus. Neurobiol Aging 1993; 14: 287–93.

47PR Rapp , M Gallagher . Preserved neuron number in the hippocampus of aged rats with spatial learning deficits. Proc Natl Acad Sci USA 1996; 93 : 9926–30.

48T Rasmussen , T Schliemann , JC Sorensen , J Zimmer , MJ West . Memory-impaired aged rats: no loss of principal hippocampal and subicular neurons. Neurobiol Aging 1996; 17: 143–47.

49PR Hof , JH Morrison . The aging brain: morphomolecular senescence of cortical circuits. Trends Neurosci 2004; 27: 607–13.

50DL Dickstein , D Kabaso , AB Rocher , JI Luebke , SL Wearne , PR Hof . Changes in the structural complexity of the aged brain. Aging Cell 2007; 6: 275–84.

51JH Morrison , PR Hof . Life and death of neurons in the aging cerebral cortex. Int Rev Neurobiol 2007; 81: 4157.

52Y Tang , JR Nyengaard , B Pakkenberg , HJ Gundersen . Age-induced white-matter changes in the human brain: a stereological investigation. Neurobiol Aging 1997; 18: 609–15.

53L Marner , JR Nyengaard , Y Tang , B Pakkenberg . Marked loss of myelinated nerve fibers in the human brain with age. J Comp Neurol 2003; 462: 144–52.

54JD Hinman , CR Abraham . What's behind the decline? The role of white matter in brain aging. Neurochem Res 2007; 32: 2023–31.

55A Peters . The effects of normal aging on myelin and nerve fibers: a review. J Neurocytol 2002; 31: 581–93.

56EA Nimchinsky , BL Sabatini , K Svoboda . Structure and function of dendritic spines. Annu Rev Physiol 2002; 64: 313–53.

57S Halpain , K Spencer , S Graber . Dynamics and pathology of dendritic spines. Prog Brain Res 2005; 147: 2937.

58O von Bohlen und Halbach , C Zacher , P Gass , K Unsicker . Age-related alterations in hippocampal spines and deficiencies in spatial memory in mice. J Neurosci Res 2006; 83: 525–31.

59JH Morrison , PR Hof . Selective vulnerability of corticocortical and hippocampal circuits in aging and Alzheimer's disease. Prog Brain Res 2002; 136: 467–86.

60M Wallace , M Frankfurt , A Arellanos , T Inagaki , V Luine . Impaired recognition memory and decreased prefrontal cortex spine density in aged female rats. Ann N Y Acad Sci 2007; 1097: 5457

61PD Coleman , DG Flood . Net dendritic stability of layer II pyramidal neurons in F344 rat entorhinal cortex from 12 to 37 months. Neurobiol Aging 1991; 12: 535–41.

62SD Hanks , DG Flood . Region-specific stability of dendritic extent in normal human aging and regression in Alzheimer's disease. I. CA1 of hippocampus. Brain Res 1991; 540: 6382.

63JD Grill , DR Riddle . Age-related and laminar-specific dendritic changes in the medial frontal cortex of the rat. Brain Res 2002; 937: 821.

64VA Alvarez , BL Sabatini . Anatomical and physiological plasticity of dendritic spines. Annu Rev Neurosci 2007; 30: 7997.

65Y Geinisman , L de Toledo-Morrell , F Morrell , IS Persina , M Rossi . Age-related loss of axospinous synapses formed by two afferent systems in the rat dentate gyrus as revealed by the unbiased stereological dissector technique. Hippocampus 1992; 2: 437–44.

66BP Rutten , NM Van Der Kolk , S Schafer Age-related loss of synaptophysin immunoreactive presynaptic boutons within the hippocampus of APP751SL, PS1M146L, and APP751SL/PS1M146L transgenic mice. Am J Pathol 2005; 167: 161–73.

67J Tigges , JG Herndon , DL Rosene . Mild age-related changes in the dentate gyrus of adult rhesus monkeys. Acta Anat (Basel) 1995; 153: 3948.

68J Tigges , JG Herndon , DL Rosene . Preservation into old age of synaptic number and size in the supragranular layer of the dentate gyrus in rhesus monkeys. Acta Anat (Basel) 1996; 157: 6372.

70L Shi , MC Linville , EW Tucker , WE Sonntag , JK Brunso-Bechtold . Differential effects of aging and insulin-like growth factor-1 on synapses in CA1 of rat hippocampus. Cereb Cortex 2005; 15: 571–77.

71SW Scheff , DA Price , DL Sparks . Quantitative assessment of possible age-related change in synaptic numbers in the human frontal cortex. Neurobiol Aging 2001; 22: 355–65.

72L Shi , H Pang , MC Linville , AN Bartley , AE Argenta , JK Brunso-Bechtold . Maintenance of inhibitory interneurons and boutons in sensorimotor cortex between middle and old age in Fischer 344 X Brown Norway rats. J Chem Neuroanat 2006; 32: 4653.

74CA Barnes . Long-term potentiation and the ageing brain. Philos Trans R Soc Lond B Biol Sci 2003; 358 (1432): 765–72.

75M Gallagher . Aging and hippocampal/cortical circuits in rodents. Alzheimer Dis Assoc Disord 2003; 17 (suppl 2): S457.

76ES Rosenzweig , CA Barnes . Impact of aging on hippocampal function: plasticity, network dynamics, and cognition. Prog Neurobiol 2003; 69: 143–79.

77IA Wilson , M Gallagher , H Eichenbaum , H Tanila . Neurocognitive aging: prior memories hinder new hippocampal encoding. Trends Neurosci 2006; 29: 662–70.

78HY Zhang , ML Watson , M Gallagher , MM Nicolle . Muscarinic receptor-mediated GTP-Eu binding in the hippocampus and prefrontal cortex is correlated with spatial memory impairment in aged rats. Neurobiol Aging 2007; 28: 619–26.

79G Schoenbaum , B Setlow , MP Saddoris , M Gallagher . Encoding changes in orbitofrontal cortex in reversal-impaired aged rats. J Neurophysiol 2006; 95 1509–17.

80CL LaSarge , KS Montgomery , C Tucker Deficits across multiple cognitive domains in a subset of aged Fischer 344 rats. Neurobiol Aging 2007; 28: 928–36.

81G Segovia , A Porras , A Del Arco , F Mora . Glutamatergic neurotransmission in aging: a critical perspective. Mech Ageing Dev 2001; 122: 129.

82EK Michaelis . Molecular biology of glutamate receptors in the central nervous system and their role in excitotoxicity, oxidative stress and aging. Prog Neurobiol 1998; 54: 369415.

84KR Magnusson . The aging of the NMDA receptor complexs. Front Biosci 1998; 3: 7080.

85K Yamada , T Nabeshima . Changes in NMDA receptor/nitric oxide signaling pathway in the brain with aging. Microsc Res Tech 1998; 43: 6X74.

86MM Adams , JH Morrison . Estrogen and the aging hippocampal synapse. Cereb Cortex 2003;13: 1271–75.

87TC Foster . Calcium homeostasis and modulation of synaptic plasticity in the aged brain. Aging Cell. 2007; 6: 319–25.

89A Simonyi , LA Miller , GY Sun . Region-specific decline in the expression of metabotropic glutamate receptor 7 mRNA in rat brain during aging. Brain Res Mol Brain Res 2000; 82: 101–06.

90A Simonyi , RT Ngomba , M Storto Expression of groups I and II metabotropic glutamate receptors in the rat brain during aging. Brain Res 2005; 1043: 95106.

91TG Hedberg , J Velísková , EF Sperber , ML Nunes , SL Moshé . Age-related differences in NMDA/metabotropic glutamate receptor-binding in rat substantia nigra. Int J Dev Neurosci 2003; 21: 95103.

93MR Domenici , A Pintor , RL Potenza Metabotropic glutamate receptor 5 (mGluR5)-mediated phosphoinositide hydrolysis and NMDA-potentiating effects are blunted in the striatum of aged rats: a possible additional mechanism in striatal senescence. Eur J Neurosci 2003; 17: 2047–55.

94RS Sohal , S Agarwal , BH Sohal . Oxidative stress and aging in the Mongolian gerbil (Meriones unguiculatus). Mech Ageing Dev 1995; 81: 1525.

95MJ Forster , A Dubey , KM Dawson , WA Stutts , H Lal , RS Sohal . Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain. Proc Natl Acad Sci U S A 1996; 93: 4765–69.

96RS Sohal , R Weindruch . Oxidative stress, caloric restriction, and aging. Science 1996; 273: 5963.

97ML Hamilton , H Van Remmen , JA Drake Does oxidative damage to DNA increase with age? Proc Natl Acad Sci U S A 2001; 98: 10469–74.

98S Agarwal , RS Sohal . Relationship between susceptibility to protein oxidation, aging, and maximum lifespan potential of different species. Exp Gerontol 1996; 31: 365–72.

99TS Chen , JP Richie Jr., CA Lang . The effect of aging on glutathione and cysteine levels in different regions of the mouse brain. Proc Soc Exp Biol Med 1989; 190: 399402.

100G Rao , E Xia , A Richardson . Effect of age on the expression of antioxidant enzymes in male Fischer F344 rats. Mech Ageing Dev 1990; 53: 4960.

101I Semsei , G Rao , A Richardson . Expression of superoxide dismutase and catalase in rat brain as a function of age. Mech Ageing Dev 1991; 58: 1319.

102CP LeBel , SC Bondy . Oxidative damage and cerebral aging. Prog Neurobiol 1992; 38: 601–09.

103DA Butterfield , B Howard , S Yatin Elevated oxidative stress in models of normal brain aging and Alzheimer's disease. Life Sci 1999; 65: 1883–92.

104J Liu , A Mori . Stress, aging, and brain oxidative damage. Neurochem Res 1999; 24: 1479–97.

105RS Sohal , S Agarwal , M Candas , MJ Forster , H Lal . Effect of age and caloric restriction on DNA oxidative damage in different tissues of C57BL/6 mice. Mech Ageing Dev 1994; 76: 215–24.

106RS Sohal , HH Ku , S Agarwal , MJ Forster , H Lal . Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse. Mech Ageing Dev 1994; 74: 121–33.

107MM Nicolle , J Gonzalez , K Sugaya Signatures of hippocampal oxidative stress in aged spatial learning-impaired rodents. Neuroscience 2001; 107: 415–31.

108JM Carney , PE Starke-Reed , CN Oliver Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone. Proc Natl Acad Sci USA 1991; 88: 3633–36.

109Y Wang , CF Chang , J Chou Dietary supplementation with blueberries, spinach, or spirulina reduces ischemic brain damage. Exp Neurol 2005; 193: 7584.

111V Calabrese , E Guagliano , M Sapienza Redox regulation of cellular stress response in aging and neurodegenerative disorders: role of vitagenes. Neurochem Res 2007; 32: 757–73.

112W Dröge , HM Schipper . Oxidative stress and aberrant signaling in aging and cognitive decline. Aging Cell 2007; 6: 361–70.

113A Taguchi , MF White . Insulin-like signalling, nutrient homeostasis, and life span. Annu Rev Physiol 2008; 70: 191212.

114TA Prolla , MP Mattson . Molecular mechanisms of brain aging and neurodegenerative disorders: lessons from dietary restriction. Trends Neurosci 2001; 24: S21S31.

115SM Ye , RW Johnson . An age-related decline in interleukin-10 may contribute to the increased expression of interleukin-6 in brain of aged mice. Neuroimmunomodulation 2001; 9: 183–92.

116KG Sharman , EH Sharman , E Yang , SC Bondy . Dietary melatonin selectively reverses age-related changes in cortical cytokine mRNA levels, and their responses to an inflammatory stimulus. Neurobiol Aging 2002; 23: 633–38.

117JD Weaver , MH Huang , M Albert , T Harris , JW Rowe , TE Seeman . Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology 2002; 59: 371–78.

118AM Bodles , SW Barger . Cytokines and the aging brain – what we don't know might help us. Trends Neurosci 2004; 27: 621–26.

119R Weindruch , T Kayo , CK Lee , TA Prolla . Gene-expression profiling of aging using DNA microarrays. Mech Ageing Dev 2002;123: 177–93.

120JE Galvin , SD Ginsberg . Expression profiling in the aging brain: a perspective. Ageing Res Rev 2005; 4: 529–47.

121A Terao , A Apte-Deshpande , L Dousman Immune response gene expression increases in the aging murine hippocampus. J Neuroimmunol 2002; 132: 99112.

122AM Lynch , MA Lynch . The age-related increase in IL-1 type I receptor in rat hippocampus is coupled with an increase in caspase-3 activation. Eur J Neurosci 2002; 15: 1779–88.

123MA Lynch . What is the biological significance of an age-related increase in IL-1beta in hippocampus? Mol Psychiatry 1999; 4: 1518.

125A Nimmerjahn , F Kirchhoff , F Helmchen . Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 2005; 308: 1314–18.

126G Raivich . Like cops on the beat: the active role of resting microglia. Trends Neurosci 2005; 28: 571–73

127UK Hanisch , H Kettenmann . Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 2007; 10: 1387–94.

129EW Boddeke , I Meigel , S Frentzel , K Biber , LQ Renn , P Gebicke-Härter . Functional expression of the fractalkine (CX3C) receptor and its regulation by lipopolysaccharide in rat microglia. Eur J Pharmacol 1999;374: 309–13.

130UK Hanisch . Microglia as a source and target of cytokines. Glia 2002; 40: 140–55.

131D Davalos , J Grutzendler , G Yang ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 2005; 8: 752–58.

132B Becher , A Prat , JP Antel . Brain-immune connection: immuno-regulatory properties of CNS-resident cells. Glia 2000; 29: 293304.

133CT Ekdahl , JH Claasen , S Bonde , Z Kokaia , O Lindvall . Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci USA 2003; 100: 13632–637.

134ML Monje , H Toda , TD Palmer . Inflammatory blockade restores adult hippocampal neurogenesis. Science 2003; 302: 1760–65.

135C Gemma , AD Bachstetter , MJ Cole , M Fister , C Hudson , PC Bickford . Blockade of caspase-1 increases neurogenesis in the aged hippocampus. Eur J Neurosci 2007; 26: 2795–803.

136R Griffin , R Nally , Y Nolan , Y McCartney , J Linden , MA Lynch . The age-related attenuation in long-term potentiation is associated with microglial activation. J Neurochem 2006; 99: 1263–72.

137P Casolini , A Catalani , AR Zuena , L Angelucci . Inhibition of COX-2 reduces the age-dependent increase of hippocampal inflammatory markers, corticosterone secretion, and behavioral impairments in the rat. J Neurosci Res 2002; 68: 337–43.

138CJ Wilson , CE Finch , HJ Cohen . Cytokines and cognition–the case for a head-to-toe inflammatory paradigm. J Am Geriatr Soc 2002; 50: 2041–56.

140FO Maher , DS Martin , MA Lynch . Increased IL-1beta in cortex of aged rats is accompanied by downregulation of ERK and PI-3 kinase. Neurobiol Aging 2004; 25: 795806.

141Y Nolan , FO Maher , DS Martin Role of interleukin-4 in regulation of age-related inflammatory changes in the hippocampus. J Biol Chem 2005; 280: 9354–62.

142VH Perry , MK Matyszak , S Fearn . Altered antigen expression of microglia in the aged rodent CNS. Glia 1993; 7: 6067.

143S Kullberg , H Aldskogius , B Ulfhake . Microglial activation, emergence of ED1-expressing cells and clusterin upregulation in the aging rat CNS, with special reference to the spinal cord. Brain Res 2001; 899: 169–86.

144CC Stichel , H Luebbert . Inflammatory processes in the aging mouse brain: participation of dendritic cells and T-cells. Neurobiol Aging 2007; 28: 1507–21.

145MK Schindler , ME Forbes , ME Robbins Aging-dependent changes in the radiation response of the adult rat brain. Int J Radiat Oncol Biol Phys 2008; 70: 826–34.

146JA Sloane , W Hollander , MB Moss , DL Rosene , CR Abraham . Increased microglial activation and protein nitration in white matter of the aging monkey. Neurobiol Aging 1999; 20: 395405.

147JR Conde , WJ Streit . Microglia in the aging brain. J Neuropathol Exp Neurol 2006; 65: 199203.

148JE Simpson , PG Ince , CE Higham Microglial activation in white-matter lesions and nonlesional white matter of ageing brains. Neuropathol Appl Neurobiol 2007; 33: 670–83.

149JM Long , AN Kalehua , NJ Muth Stereological analysis of astrocyte and microglia in aging mouse hippocampus. Neurobiol Aging 1998; 19: 497503.

150WJ Streit . Microglia and neuroprotection: implications for Alzheimer's disease. Brain Res Brain Res Rev 2005; 48: 234–39.

151Y Ziv , N Ron , O Butovsky Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci 2006; 9: 268–75.

152I Glezer , AR Simard , S Rivest . Neuroprotective role of the innate immune system by microglia. Neuroscience 2007; 147: 867–83.

153K Nakajima , Y Tohyama , S Maeda , S Kohsaka , T Kurihara . Neuronal regulation by which microglia enhance the production of neurotrophic factors for GABAergic, catecholaminergic, and cholinergic neurons. Neurochem Int 2007; 50: 807820.

154AY Lai , KG Todd . Differential regulation of trophic and proinflammatory microglial effectors is dependent on severity of neuronal injury. Glia 2008; 56: 259–70.

155A Sierra , AC Gottfried-Blackmore , BS McEwen , K Bulloch . Microglia derived from aging mice exhibit an altered inflammatory profile. Glia 2007; 55: 412–24.

156JA Joseph , B Shukitt-Hale , G Casadesus , D Fisher . Oxidative stress and inflammation in brain aging: nutritional considerations. Neurochem Res 2005; 30: 927–35.

157GS Roth , DK Ingram , JA Joseph . Nutritional interventions in aging and age-associated diseases. Ann N Y Acad Sci 2007; 1114: 369–71.

158PC Bickford , T Gould , L Briederick Antioxidant-rich diets improve cerebellar physiology and motor learning in aged rats. Brain Res 2000; 866: 211–17.

160P Goyarzu , DH Malin , FC Lau Blueberry-supplemented diet: effects on object recognition memory and nuclear factor-kappa B levels in aged rats. Nutr Neurosci 2004 Apr; 7: 7583.

161B Shukitt-Hale , A Carey , L Simon , DA Mark , JA Joseph . Effects of Concord grape juice on cognitive and motor deficits in aging. Nutrition 2006; 22: 295302.

162NS Kamel , J Gammack , O Cepeda , JH Flaherty . Antioxidants and hormones as anti-aging therapies: high hopes, disappointing results. Cleve Clin J Med 2006; 73: 1049–56.

163F Grodstein , JH Kang , RJ Glynn , NR Cook , JM Gaziano . A randomized trial of beta carotene supplementation and cognitive function in men: the Physicians' Health Study II. Arch Intern Med 2007; 167: 2184–80.

164G McNeill , A Avenell , MK Campbell Effect of multivitamin and multimineral supplementation on cognitive function in men and women aged 65 years and over: a randomised controlled trial. Nutr J 2007; 6: 10.

168B Shukitt-Hale , AN Carey , D Jenkins , BM Rabin , JA Joseph . Beneficial effects of fruit extracts on neuronal function and behavior in a rodent model of accelerated aging. Neurobiol Aging 2007; 28: 1187–94.

169AY Bekker , EJ Weeks . Cognitive function after anaesthesia in the elderly. Best Pract Res Clin Anaesthesiol 2003; 17: 259–72.

170R Cohendy , A Brougere , P Cuvillon . Anaesthesia in the older patient. Curr Opin Clin Nutr Metab Care 2005; 8: 17–1.

171WC Levine , V Mehta , G Landesberg . Anesthesia for the elderly: selected topics. Curr Opin Anaesthesiol 2006; 19: 320–24.

172DJ Culley , Z Xie , G Crosby . General anesthetic-induced neurotoxicity: an emerging problem for the young and old? Curr Opin Anaesthesiol 2007; 20: 408–13.

173M Perouansky . General anesthetics and long-term neurotoxicity. Handb Exp Pharmacol 2008; 182: 143–57.

174S Kyrkanides , MK O'Banion , PE Whiteley , JC Daeschner , JA Olschowka . Enhanced glial activation and expression of specific CNS inflammation-related molecules in aged versus young rats following cortical stab injury. J Neuroimmunol 2001; 119: 269–77.

175A Popa-Wagner , I Badan , L Walker , S Groppa , N Patrana , C Kessler . Accelerated infarct development, cytogenesis and apoptosis following transient cerebral ischemia in aged rats. Acta Neuropathol (Berl) 2007; 113: 277–93.

176I Lamproglou , QM Chen , G Boisserie Radiation-induced cognitive dysfunction: an experimental model in the old rat. Int J Radiat Oncol Biol Phys 1995; 31: 6570.

177I Lamproglou , F Baillet , G Boisserie , JJ Mazeron , JY Delattre . The influence of age on radiation-induced cognitive deficit: experimental studies on brain irradiation of 30 Gy in 10 sessions and 12 hours in the Wistar rat at 1 1/2, 4 and 18 months age. Can J Physiol Pharmacol 2002; 80: 679–85.

179LM Deangelis . Primary CNS lymphoma: treatment with combined chemotherapy and radiotherapy. J Neurooncol 1999; 43: 249–57.

180MH Swennen , JE Bromberg , TD Witkamp , CH Terhaard , TJ Postma , MJ Taphoorn . Delayed radiation toxicity after focal or whole brain radiotherapy for low-grade glioma. J Neurooncol 2004; 66: 333–39.

181AM Omuro , LS Ben-Porat , KS Panageas , Delayed neurotoxicity in primary central nervous system lymphoma. Arch Neurol 2005; 62: 15951600.

182RM Barrientos , EA Higgins , JC Biedenkapp Peripheral infection and aging interact to impair hippocampal memory consolidation. Neurobiol Aging 2006; 27: 723–32.

183MG Frank , MV Baratta , DB Sprunger , LR Watkins , SF Maier . Microglia serve as a neuroimmune substrate for stress-induced potentiation of CNS pro-inflammatory cytokine responses. Brain Behav Immun 2007; 21: 4759.

184VH Perry , C Cunningham , C Holmes . Systemic infections and inflammation affect chronic neurodegeneration. Nat Rev Immunol 2007; 7: –67.

187B Viviani , F Gardoni , M Marinovich . Cytokines and neuronal ion channels in health and disease. Int Rev Neurobiol 2007; 82: 247–63.

188M Pickering , D Cumiskey , JJ O'Connor . Actions of TNF-alpha on glutamatergic synaptic transmission in the central nervous system. Exp Physiol 2005; 90: 663–70.

189M Pickering , JJ O'Connor . Pro-inflammatory cytokines and their effects in the dentate gyrus. Prog Brain Res 2007; 163: 339–54.

192EJ Vereyken , H Bajova , S Chow , PN de Graan , DL Gruol . Chronic interleukin-6 alters the level of synaptic proteins in hippocampus in culture and in vivo. Eur J Neurosci 2007; 25: 3605–16.

193A Bessis , C Béchade , D Bernard Microglial control of neuronal death and synaptic properties. Glia 2007; 55: 233–38.

194BD Trapp , JR Wujek , GA Criste Evidence for synaptic stripping by cortical microglia. Glia 2007; 55: 360–68.

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Reviews in Clinical Gerontology
  • ISSN: 0959-2598
  • EISSN: 1469-9036
  • URL: /core/journals/reviews-in-clinical-gerontology
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