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Morphological changes in nerve cells during normal aging

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Abstract

During normal aging, widespread loss of nerve cells does not occur. Neuronal loss is limited to restricted regions of the nervous system and is slight (probably no more than 10%). The commonest age-related structural changes undergone by nerve cells are as follows: dendrites decrease in number and length and many dendritic spines are lost; axons decrease in number and their myelin sheaths may become less compact and undergo segmental demyelination followed by remyelination; and significant loss of synapses occurs. These changes probably make a significant contribution to the behavioral impairment and cognitive decline that often accompany normal aging.

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References

  • Adams I, Jones DG (1982) Quantitative ultrastructural changes in rat cortical synapses during early-, mid- and late-adulthood. Brain Res 239:349–363

    Article  PubMed  CAS  Google Scholar 

  • Adinolfi A, Yamuy J, Morales FR, Chase MH (1991) Segmental demyelination in peripheral nerves of old cats. Neurobiol Aging 12:175–179

    Article  PubMed  CAS  Google Scholar 

  • Ahmad B, Spear PD (1993) Effects of aging on the size, density, and number of rhesus monkey lateral geniculate neurons. J Comp Neurol 334:631–643

    Article  PubMed  CAS  Google Scholar 

  • Aldskogius H, Risling M (1989) Number of dorsal root ganglion neurons and axons in cats of different ages. Exp Neurol 106:70–73

    Article  PubMed  CAS  Google Scholar 

  • Aston-Jones G, Rogers J, Shaver RD, Dinan TG, Moss DE (1985) Age-impaired impulse flow from nucleus basalis to cortex. Nature 318:462–464

    Article  PubMed  CAS  Google Scholar 

  • Bondareff W, Geinisman Y (1976) Loss of synapses in the dentate gyrus of the senescent rat. Am J Anat 145:129–136

    Article  PubMed  CAS  Google Scholar 

  • Bowley MP, Cabral H, Rosene DL, Peters A (2010) Age changes in myelinated nerve fibers of the cingulate bundle and corpus callosum in the rhesus monkey. J Comp Neurol 518:3046–3064

    Article  PubMed  Google Scholar 

  • Brody H (1955) Organization of the cerebral cortex. III. A study of aging in the human cerebral cortex. J Comp Neurol 102:511–556

    Article  PubMed  CAS  Google Scholar 

  • Casey MA, Feldman ML (1985) Aging in the rat medial nucleus of the trapezoid body. II. Electron microscopy. J Comp Neurol 232:401–413

    Article  PubMed  CAS  Google Scholar 

  • Ceballos D, Cuadras J, Verdú E, Navarro X (1999) Morphometric and ultrastructural changes with ageing in mouse peripheral nerve. J Anat 195:563–576

    Article  PubMed  Google Scholar 

  • Cepurna WO, Kayton RJ, Johnson EC, Morrison JC (2005) Age related optic nerve axonal loss in adult Brown Norway rats. Exp Eye Res 80:877–884

    Article  PubMed  CAS  Google Scholar 

  • Cotard-Bartley MP, Secchi J, Glomot R, Cavanagh JB (1981) Spontaneous degenerative lesions of peripheral nerves in aging rats. Vet Pathol 18:110–113

    PubMed  CAS  Google Scholar 

  • Cragg BG (1975) The density of synapses and neurons in normal, mentally defective and ageing human brains. Brain 98:81–90

    Article  PubMed  CAS  Google Scholar 

  • Curcio CA, Coleman PD (1982) Stability of neuron number in cortical barrels of aging mice. J Comp Neurol 212:158–172

    Article  PubMed  CAS  Google Scholar 

  • Delorenzi E (1931) Costanza numerica delle cellule del Purkinje in individui di varia età. Boll Soc It Biol Sper 6:80–82

    Google Scholar 

  • Dorfman LJ, Bosley TM (1979) Age-related changes in peripheral and central nerve conduction in man. Neurology 29:38–44

    PubMed  CAS  Google Scholar 

  • Duan H, Wearne SL, Rocher AB, Macedo A, Morrison JH, Hof PR (2003) Age-related dendritic and spine changes in corticocortically projecting neurons in macaque monkeys. Cer Cortex 13:950–961

    Article  Google Scholar 

  • Dumitriu D, Hao J, Hara Y, Kaufmann J, Janssen WGM, Lou W, Rapp PR, Morrison JH (2010) Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment. J Neurosci 30:7507–7515

    Article  PubMed  CAS  Google Scholar 

  • Feldman ML, Peters A (1998) Ballooning of myelin sheaths in normally aged macaques. J Neurocytol 27:605–614

    Article  PubMed  CAS  Google Scholar 

  • Fujisawa K (1992) Rat spinal ganglion neurone: quantitative aspects of its development and involution. In: Fujisawa K, Morimatsu Y (eds) Development and involution of neurones. Japan Scientific Societies Press, Tokyo, pp 151–165

    Google Scholar 

  • Geinisman Y (1979) Loss of axosomatic synapses in the dentate gyrus of aged rats. Brain Res 168:485–492

    Article  PubMed  CAS  Google Scholar 

  • Geinisman Y, Bondareff W, Dodge JT (1978) Dendritic atrophy in the dentate gyrus of the senescent rat. Am J Anat 152:321–330

    Article  PubMed  CAS  Google Scholar 

  • Gibson PH (1983) EM study of the numbers of cortical synapses in the brains of ageing people and people with Alzheimer-type dementia. Acta Neuropathol 62:127–133

    Article  PubMed  CAS  Google Scholar 

  • Gilmore SA (1972) Spinal nerve root degeneration in aging laboratory rats: a light microscopic study. Anat Rec 174:251–257

    Article  PubMed  CAS  Google Scholar 

  • Goemaere-Vanneste J, van den Bosch de Aguilar P (1987) Étude des fibres nerveuses périphériques au cours du viellissement chez le rat. La Cellule 74:263–280

    PubMed  CAS  Google Scholar 

  • Gong G, Rosa-Neto P, Carbonell F, Chen ZJ, He Y, Evans AC (2009) Age- and gender-related differences in the cortical anatomical network. J Neurosci 29:15684–15693

    Article  PubMed  CAS  Google Scholar 

  • Griffiths IR, Duncan ID, McQueen A (1975) Age changes in the dorsal and ventral lumbar nerve roots of dogs. Acta Neuropathol 32:75–85

    Article  PubMed  CAS  Google Scholar 

  • Grover-Johnson N, Spencer PS (1981) Peripheral nerve abnormalities in aging rats. J Neuropathol Exp Neurol 40:155–165

    Article  PubMed  CAS  Google Scholar 

  • Haug H (1985) Are neurons of the human cerebral cortex really lost during aging? A morphometric examination. In: Traber J, Gispen WH (eds) Senile dementia of the Alzheimer type. Springer-Verlag, Berlin, pp 150–163

    Google Scholar 

  • Haug H, Kühl S, Mecke E, Sass N-L, Wasner K (1984) The significance of morphometric procedures in the investigation of age changes in cytoarchitectonic structures of human brain. J Hirnforsch 25:353–374

    PubMed  CAS  Google Scholar 

  • Hinds JW, McNelly NA (1977) Aging of the rat olfactory bulb: growth and atrophy of constituent layers and changes in size and number of mitral cells. J Comp Neurol 171:345–368

    Article  Google Scholar 

  • Hinds JW, McNelly NA (1979) Aging in the rat olfactory bulb: quantitative changes in mitral cell organelles and somato-dendritic synapses. J Comp Neurol 184:811–819

    Article  PubMed  CAS  Google Scholar 

  • Hodge CF (1894) Changes in ganglion cells from birth to senile death. Observations on man and honey-bee. J Physiol 17:129–134

    Google Scholar 

  • Jermakowicz WJ, Casagrande VA (2007) Neural networks a century after Cajal. Brain Res Rev 55:264–284

    Article  PubMed  Google Scholar 

  • Johnson BM, Miao M, Sadun AA (1987) Age-related decline of human optic nerve axon population. Age 10:5–9

    Article  Google Scholar 

  • Kabaso D, Coskren PJ, Henry BI, Hof PR, Wearne SL (2009) The electrotonic structure of pyramidal neurons contributing to prefrontal cortical circuits in macaque monkeys is significantly altered in aging. Cer Cortex 19:2248–2268

    Article  Google Scholar 

  • Karlsson M, Hildebrand C (1996) Postnatal development and aging of the rat ventral root L5: electron microscopic and immunohistochemical studies. J Comp Neurol 364:211–218

    Article  PubMed  CAS  Google Scholar 

  • Kawamura Y, Okazaki H, O’Brien PC, Dyck PJ (1977) Lumbar motoneurons of man: I. Number and diameter histogram of alpha and gamma axons of ventral root. J Neuropathol Exp Neurol 36:853–860

    Article  PubMed  CAS  Google Scholar 

  • Keuker JIH, de Biurrun G, Luiten PGM, Fuchs E (2004) Preservation of hippocampal neuron numbers and hippocampal subfield volumes in behaviorally characterized aged tree shrews. J Comp Neurol 468:509–517

    Article  PubMed  Google Scholar 

  • Knox CA, Kokmen E, Dyck PJ (1989) Morphometric alteration of rat myelinated fibers with aging. J Neuropathol Exp Neurol 48:119–139

    Article  PubMed  CAS  Google Scholar 

  • Komiya Y (1980) Slowing with age of the rate of slow axonal flow in bifurcating axons of rat dorsal root ganglion cells. Brain Res 183:477–480

    Article  PubMed  CAS  Google Scholar 

  • Koneff H (1887) Beiträge zur Kenntnis in den Nervenzellen der peripheren Ganglien. Mitteilungen der Naturforschenden Gesellschaft in Bern, pp 13–44

  • Ledda M, Barni L, Altieri L, Pannese E (2000) Decrease in the nucleo-cytoplasmic volume ratio of rabbit spinal ganglion neurons with age. Neurosci Lett 286:171–174

    Article  PubMed  CAS  Google Scholar 

  • Leuba G (1983) Aging of dendrites in the cerebral cortex of the mouse. Neuropathol Appl Neurobiol 9:467–475

    Article  PubMed  CAS  Google Scholar 

  • Leuba G, Kraftsik R (1994) Changes in volume, surface estimate, three-dimensional shape and total number of neurons of the human primary visual cortex from midgestation until old age. Anat Embryol 190:351–366

    Article  PubMed  CAS  Google Scholar 

  • Madeira MD, Sousa N, Santer RM, Paula-Barbosa MM, Gundersen HJG (1995) Age and sex do not affect the volume, cell numbers, or cell size of the suprachiasmatic nucleus of the rat: an unbiased stereological study. J Comp Neurol 361:585–601

    Article  PubMed  CAS  Google Scholar 

  • Markus EJ, Petit TL, LeBoutillier JC (1987) Synaptic structural changes during development and aging. Develop Brain Res 35:239–248

    Article  Google Scholar 

  • Marner L, Nyengaard JR, Tang Y, Pakkenberg B (2003) Marked loss of myelinated nerve fibers in the human brain with age. J Comp Neurol 462:144–152

    Article  PubMed  Google Scholar 

  • Martinelli C, Sartori P, Ledda M, Pannese E (2006) A study of mitochondria in spinal ganglion neurons during life: quantitative changes from youth to extremely advanced age. Tissue Cell 38:93–98

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto A, Okada R, Arai Y (1982) Synaptic changes in the hypothalamic arcuate nucleus of old male rats. Exp Neurol 78:583–590

    Article  PubMed  CAS  Google Scholar 

  • McQuarrie IG, Brady ST, Lasek RJ (1989) Retardation in the slow axonal transport of cytoskeletal elements during maturation and aging. Neurobiol Aging 10:359–365

    Article  PubMed  CAS  Google Scholar 

  • Merrill DA, Chiba AA, Tuszynski MH (2001) Conservation of neuronal number and size in the entorhinal cortex of behaviorally characterized aged rats. J Comp Neurol 438:445–456

    Article  PubMed  CAS  Google Scholar 

  • Mohammed HA, Santer RM (2001) Total neuronal numbers of rat lumbosacral primary afferent neurons do not change with age. Neurosci Lett 304:149–152

    Article  PubMed  CAS  Google Scholar 

  • Moore SA, Peterson RG, Felten DL, O’Connor BL (1982) Ultrastructural axonal pathology in experimentally diabetic and aging control rats. Brain Res Bull 8:317–323

    Article  PubMed  CAS  Google Scholar 

  • Morrison JH, Hof PR (1997) Life and death of neurons in the aging brain. Science 278:412–419

    Article  PubMed  CAS  Google Scholar 

  • Nakamura S, Akiguchi I, Kameyama M, Mizuno N (1985) Age-related changes of pyramidal cell basal dendrites in layers III and V of human motor cortex: a quantitative Golgi study. Acta Neuropathol 65:281–284

    Article  PubMed  CAS  Google Scholar 

  • Ochoa J, Mair WG (1969) The normal sural nerve in man. II. Changes in the axons and Schwann cells due to aging. Acta Neuropathol 13:217–239

    Article  PubMed  CAS  Google Scholar 

  • Pakkenberg B, Gundersen HJG (1997) Neocortical neuron number in humans: effect of sex and age. J Comp Neurol 384:312–320

    Article  PubMed  CAS  Google Scholar 

  • Peinado MA, Martinez M, Pedrosa JA, Quesada A, Peinado JM (1993) Quantitative morphological changes in neurons and glia in the frontal lobe of the aging rat. Anat Rec 237:104–108

    Article  PubMed  CAS  Google Scholar 

  • Pestronk A, Drachman DB, Griffin JW (1980) Effects of aging on nerve sprouting and regeneration. Exp Neurol 70:65–82

    Article  PubMed  CAS  Google Scholar 

  • Peters A (2002) The effects of normal aging on myelin and nerve fibers: a review. J Neurocytol 31:581–593

    Article  PubMed  Google Scholar 

  • Peters A, Sethares C (1993) Aging and the Meynert cells in rhesus monkey primary visual cortex. Anat Rec 236:721–729

    Article  PubMed  CAS  Google Scholar 

  • Peters A, Sethares C (2002) Aging and the myelinated fibers in prefrontal cortex and corpus callosum of the monkey. J Comp Neurol 442:277–291

    Article  PubMed  Google Scholar 

  • Peters A, Sethares C, Moss MB (1998) The effects of aging on layer 1 in area 46 of prefrontal cortex in the rhesus monkey. Cer Cortex 8:671–684

    Article  CAS  Google Scholar 

  • Peters A, Moss MB, Sethares C (2000) Effects of aging on myelinated nerve fibers in monkey primary visual cortex. J Comp Neurol 419:364–376

    Article  PubMed  CAS  Google Scholar 

  • Peters A, Sethares C, Luebke JI (2008) Synapses are lost during aging in the primate prefrontal cortex. Neuroscience 152:970–981

    Article  PubMed  CAS  Google Scholar 

  • Peters A, Sethares C, Moss MB (2010) How the primate fornix is affected by age. J Comp Neurol 518:3962–3980

    Article  PubMed  Google Scholar 

  • Pilcz A (1895) Beitrag zur Lehre von der Pigmententwickelung in den Nervenzellen. Arbeiten aus dem Institut für Anatomie und Physiologie des Centralnervensystems an der Wiener Universität III Heft, pp 123–139

  • Rafols JA, Cheng HW, McNeill TH (1989) Golgi study of the mouse striatum: age-related dendritic changes in different neuronal populations. J Comp Neurol 279:212–227

    Article  PubMed  CAS  Google Scholar 

  • Rogers J, Zornetzer SF, Bloom FE (1981) Senescent pathology of cerebellum: Purkinje neurons and their parallel fiber afferents. Neurobiol Aging 2:15–25

    Article  PubMed  CAS  Google Scholar 

  • Sandell JH, Peters A (2001) Effects of age on nerve fibers in the rhesus monkey optic nerve. J Comp Neurol 429:541–553

    Article  PubMed  CAS  Google Scholar 

  • Sandell JH, Peters A (2003) Disrupted myelin and axon loss in the anterior commissure of the aged rhesus monkey. J Comp Neurol 466:14–30

    Article  PubMed  Google Scholar 

  • Scheibel ME, Lindsay RD, Tomiyasu U, Scheibel AB (1975) Progressive dendritic changes in aging human cortex. Exp Neurol 47:392–403

    Article  PubMed  CAS  Google Scholar 

  • Scheibel ME, Lindsay RD, Tomiyasu U, Scheibel AB (1976) Progressive dendritic changes in the aging human limbic system. Exp Neurol 53:420–430

    Article  PubMed  CAS  Google Scholar 

  • Scheibel ME, Tomiyasu U, Scheibel AB (1977) The aging human Betz cell. Exp Neurol 56:598–609

    Article  PubMed  CAS  Google Scholar 

  • Schmidt RE, Chae HY, Parvin CA, Roth KA (1990) Neuroaxonal dystrophy in aging human sympathetic ganglia. Am J Pathol 136:1327–1338

    PubMed  CAS  Google Scholar 

  • Schulz R (1883) Ueber arteficielle, cadaveröse und pathologische Veränderungen des Rückenmarks. Neurologisches Centralblatt 2:(529–536), 553–559

    Google Scholar 

  • Sharma AK, Bajada S, Thomas PK (1980) Age changes in the tibial and plantar nerves of the rat. J Anat 130:417–428

    PubMed  CAS  Google Scholar 

  • Silverman WF, Sladek JR Jr (1991) Ultrastructural changes in magnocellular neurons from the supraoptic nucleus of aged rats. Develop Brain Res 58:25–34

    Article  CAS  Google Scholar 

  • Tanaka K, Webster HdeF (1991) Myelinated fiber regeneration after crush injury is retarded in sciatic nerves of aging mice. J Comp Neurol 308:180–187

    Article  PubMed  CAS  Google Scholar 

  • Terry RD, Deteresa R, Hansen LA (1987) Neocortical cell counts in normal human adult aging. Ann Neurol 21:530–539

    Article  PubMed  CAS  Google Scholar 

  • Thomas PK, King RHM, Sharma AK (1980) Changes with age in the peripheral nerves of the rat. An ultrastructural study. Acta Neuropathol 52:1–6

    Article  PubMed  CAS  Google Scholar 

  • Tigges J, Herndon JG, Peters A (1992) Axon terminals on Betz cell somata of area 4 in rhesus monkey throughout adulthood. Anat Rec 232:305–315

    Article  PubMed  CAS  Google Scholar 

  • Uemura E (1980) Age-related changes in prefrontal cortex of Macaca mulatta: synaptic density. Exp Neurol 69:164–172

    Article  PubMed  CAS  Google Scholar 

  • Uemura E (1985a) Age-related changes in the subiculum of Macaca mulatta: synaptic density. Exp Neurol 87:403–411

    Article  PubMed  CAS  Google Scholar 

  • Uemura E (1985b) Age-related changes in the subiculum of Macaca mulatta: dendritic branching pattern. Exp Neurol 87:412–427

    Article  PubMed  CAS  Google Scholar 

  • van den Bosch de Aguilar P, Goemaere-Vanneste J, Klosen P, Terao E (1992) Ageing changes of spinal ganglion neurons. In: Fujisawa K, Morimatsu Y (eds) Development and involution of neurones. Japan Scientific Societies Press, Tokyo, pp 109–150

    Google Scholar 

  • Vaughan DW (1977) Age-related deterioration of pyramidal cell basal dendrites in rat auditory cortex. J Comp Neurol 171:501–516

    Article  PubMed  CAS  Google Scholar 

  • Vaughan DW (1992) Effects of advancing age on peripheral nerve regeneration. J Comp Neurol 323:219–237

    Article  PubMed  CAS  Google Scholar 

  • Wagman IH, Lesse H (1952) Maximum conduction velocities of motor fibers of ulnar nerve in human subjects of various ages and sizes. J Neurophysiol 15:235–244

    PubMed  CAS  Google Scholar 

  • Xi M-C, Liu R-H, Engelhardt JK, Morales FR, Chase MH (1999) Changes in the axonal conduction velocity of pyramidal tract neurons in the aged cat. Neuroscience 92:219–225

    Article  PubMed  CAS  Google Scholar 

  • Zhang J-H, Sampogna S, Morales FR, Chase MH (1998) Age-related intra-axonal accumulation of neurofilaments in the dorsal column nuclei of the cat brainstem: a light and electron microscopic immunohistochemical study. Brain Res 797:333–338

    Article  PubMed  CAS  Google Scholar 

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    Ennio Pannese

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Pannese, E. Morphological changes in nerve cells during normal aging. Brain Struct Funct 216, 85–89 (2011). https://doi.org/10.1007/s00429-011-0308-y

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