Abstract
Numerous reports implicate increased oxidative stress in the functional and structural changes occurring in the brain and other organs as a part of the normal aging process. Dietary restriction (DR) has long been shown to be life-prolonging intervention in several species. This study was aimed to assess the potential efficacy of late-onset short term DR when initiated in 21 months old male wistar rats for 3 months on the antioxidant defense system and lipid peroxidation, cellular stress response protein HSP 70 and synaptic marker protein synapsin 1 in discrete brain regions such as cortex, hypothalamus, and hippocampus as well as liver, kidney and heart from 24 month old rats. Age-associated decline in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione, and elevated levels of lipid peroxidation was observed in brain and peripheral organ as well as increased expression of HSP 70 and reduction in synapsin 1 was observed in brain studied. Late-onset short term DR was effective in partially restoring the antioxidant status and in decreasing lipid peroxidation level as well as enhancing the expression of HSP 70 and synapsin 1 in aged rats. Late onset short term DR also prevented age-related neurodegeneration as revealed by Fluoro-Jade B staining in hippocampus and cortex regions of rat brain. Thus our current results suggest that DR initiated even in old age has the potential to improve age related decline in body functions.
Similar content being viewed by others
References
Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126
Allard JS, Heilbronn LK, Smith C, Hunt ND, Ingram DK, Ravussin E, de Cabo R (2008) In vitro cellular adaptations of indicators of longevity in response to treatment with serum collected from humans on calorie restricted diets. PLoS ONE 3:e3211
Anderson KJ, Fugaccia I, Scheff SW (2003) Fluoro-Jade B Stains quiescent and reactive astrocytes in the rodent spinal cord. J Neurotrauma 20:1223
Araki S, Goto S (2004) Dietary restriction in aged mice can partially restore impaired metabolism of apolipoprotein A-IV and C-III. Biogerontology 5:445–450
Arivazhagan P, Panneerselvam C (2002) Neurochemical changes related to ageing in the rat brain and the effect of -[alpha]-lipoic acid. Exp Gerontol 37:1489–1494
Awizio AK, Onofri F, Benfenati F, Bonaccurso E (2007) Influence of synapsin I on synaptic vesicles: an analysis by force-volume mode of the atomic force microscope and dynamic light scattering. Biophys J 93:1051–1060
Baldelli P, Fassio A, Corradi A, Cremona O, Valtorta F, Benfenati F (2005) Synapsins and neuroexocytosis: recent views from functional studies on synapsin null mutant mice. Arch Ital Biol 143:113–126
Baldelli P, Fassio A, Valtorta F, Benfenati F (2007) Lack of synapsin I reduces the readily releasable pool of synaptic vesicles at central inhibitory synapses. J Neurosci 27:13520–13531
Barja G (2004) Free radicals and aging. Trends Neurosci 27:595–600
Berchtold NC, Cribbs DH, Coleman PD, Rogers J, Head E, Kim R, Beach T, Miller C, Troncoso J, Trojanowski JQ, Zielke HR, Cotman CW (2008) Gene expression changes in the course of normal brain aging are sexually dimorphic. Proceedings of the National Academy of Sciences 105:15605–15610
Bogen IL, Boulland JL, Mariussen E, Wright MS, Fonnum F, Kao HT, Walaas SI (2006) Absence of synapsin I and II is accompanied by decreases in vesicular transport of specific neurotransmitters. J Neurochem 96:1458–1466
Bogen IL, Jensen V, Hvalby O, Walaas SI (2009) Synapsin-dependent development of glutamatergic synaptic vesicles and presynaptic plasticity in postnatal mouse brain. Neuroscience 158:231–241
Boll MC, Alcaraz-Zubeldia M, Montes S, Rios C (2008) Free copper, ferroxidase and SOD1 activities, lipid peroxidation and NO(x) content in the CSF. A different marker profile in four neurodegenerative diseases. Neurochem Res 33:1717–1723
Bonelli MA, Desenzani S, Cavallini G, Donati A, Romani AA, Bergamini E, Borghetti AF (2008) Low-level caloric restriction rescues proteasome activity and Hsc70 level in liver of aged rats. Biogerontology 9:1–10
Brown IR (2007) Heat shock proteins and protection of the nervous system. Ann N Y Acad Sci 1113:147–158
Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310
Corradi A, Zanardi A, Giacomini C, Onofri F, Valtorta F, Zoli M, Benfenati F (2008) Synapsin-I- and synapsin-II-null mice display an increased age-dependent cognitive impairment. J Cell Sci 121:3042–3051
Damjanac M, Bilan AR, Barrier L, Pontcharraud R, Anne C, Hugon J, Page G (2007) Fluoro-Jade B staining as useful tool to identify activated microglia and astrocytes in a mouse transgenic model of Alzheimer’s disease. Brain Res 1128:40–49
Dawson GR, Seabrook GR, Zheng H, Smith DW, Graham S, O’Dowd G, Bowery BJ, Boyce S, Trumbauer ME, Chen HY, Van der Ploeg LH, Sirinathsinghji DJ (1999) Age-related cognitive deficits, impaired long-term potentiation and reduction in synaptic marker density in mice lacking the beta-amyloid precursor protein. Neuroscience 90:1–13
de Pril R, Fischer DF, van Leeuwen FW (2006) Conformational diseases: an umbrella for various neurological disorders with an impaired ubiquitin-proteasome system. Neurobiol Aging 27:515–523
Deng L, Wu ZN, Han PZ (2009) Effects of different levels of food restriction on passive-avoidance memory and the expression of synapsin I in young mice. Int J Neurosci 119:291–304
Eckles KE, Dudek EM, Bickford PC, Browning MD (1997) Amelioration of age-related deficits in the stimulation of synapsin phosphorylation. Neurobiol Aging 18:213–217
Fardoun RZ, Asghar M, Lokhandwala M (2006) Role of oxidative stress in defective renal dopamine D1 receptor-G protein coupling and function in old Fischer 344 rats. Am J Physiol Renal Physiol 291:F945–F951
Fdez E, Hilfiker S (2006) Vesicle pools and synapsins: new insights into old enigmas. Brain Cell Biol 35:107–115
Ferreira A, Kao HT, Feng J, Rapoport M, Greengard P (2000) Synapsin III: developmental expression, subcellular localization, and role in axon formation. J Neurosci 20:3736–3744
Flohe L, Gunzler WA (1984) Assays of glutathione peroxidase. Methods Enzymol 105:114–121
Frier B, Locke M (2005) Preservation of heat stress induced myocardial hsp 72 in aged animals following caloric restriction. Exp Gerontol 40:615–617
Fukui H, Moraes CT (2008) The mitochondrial impairment, oxidative stress and neurodegeneration connection: reality or just an attractive hypothesis? Trends Neurosci 31:251–256
Gomez-Pinilla F, So V, Kesslak JP (2001) Spatial learning induces neurotrophin receptor and synapsin I in the hippocampus. Brain Res 904:13–19
Gordon SA, Hoffman RA, Simmons RL, Ford HR (1997) Induction of heat shock protein 70 protects thymocytes against radiation-induced apoptosis. Arch Surg 132:1277–1282
Goto S, Takahashi R, Araki S, Nakamoto H (2002) Dietary restriction initiated in late adulthood can reverse age-related alterations of protein and protein metabolism. Ann N Y Acad Sci 959:50–56
Goyary D, Sharma R (2008) Late onset of dietary restriction reverses age-related decline of malate–aspartate shuttle enzymes in the liver and kidney of mice. Biogerontology 9:11–18
Guo ZH, Mattson MP (2000) In vivo 2-deoxyglucose administration preserves glucose and glutamate transport and mitochondrial function in cortical synaptic terminals after exposure to amyloid beta-peptide and iron: evidence for a stress response. Exp Neurol 166:173–179
Guo Z, Ersoz A, Butterfield DA, Mattson MP (2000) Beneficial effects of dietary restriction on cerebral cortical synaptic terminals: preservation of glucose and glutamate transport and mitochondrial function after exposure to amyloid beta-peptide, iron, and 3-nitropropionic acid. J Neurochem 75:314–320
Hamilton ML, Van Remmen H, Drake JA, Yang H, Guo ZM, Kewitt K (2001) Does oxidative damage to DNA increase with age? PNAS 98:10469–10474
Hilfiker S, Benfenati F, Doussau F, Nairn AC, Czernik AJ, Augustine GJ, Greengard P (2005) Structural domains involved in the regulation of transmitter release by synapsins. J Neurosci 25:2658–2669
Ingram DK, Anson RM, de Cabo R, Mamczarz J, Zhu M, Mattison J, Lane MA, Roth GS (2004) Development of calorie restriction mimetics as a prolongevity strategy. Ann N Y Acad Sci 1019:412–423
Karunanithi S, Barclay JW, Robertson RM, Brown IR, Atwood HL (1999) Neuroprotection at Drosophila synapses conferred by prior heat shock. J Neurosci 19:4360–4369
Karunanithi S, Barclay JW, Brown IR, Robertson RM, Atwood HL (2002) Enhancement of presynaptic performance in transgenic Drosophila overexpressing heat shock protein Hsp70. Synapse 44:8–14
Kaur M, Sharma S, Kaur G (2008) Age-related impairments in neuronal plasticity markers and astrocytic GFAP and their reversal by late-onset short term dietary restriction. Biogerontology 9:441–454
Kim HG, Hong SM, Kim SJ, Park HJ, Jung HI, Lee YY, Moon JS, Lim HW, Park EH, Lim CJ (2003) Age-related changes in the activity of antioxidant and redox enzymes in rats. Mol Cells 16:278–284
Kono Y (1978) Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 186:189–195
Kovtun IV, Liu Y, Bjoras M, Klungland A, Wilson SH, McMurray CT (2007) OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells. Nature 447:447–452
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
Lee J, Duan W, Long JM, Ingram DK, Mattson MP (2000) Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats. J Mol Neurosci 15:99–108
Leuner B, Kozorovitskiy Y, Gross CG, Gould E (2007) Diminished adult neurogenesis in the marmoset brain precedes old age. Proc Natl Acad Sci USA 104:17169–17173
Mancuso M, Siciliano G, Filosto M, Murri L (2006) Mitochondrial dysfunction and Alzheimer’s disease: new developments. J Alzheimers Dis 9:111–117
Mancuso C, Scapagini G, Curro D, Giuffrida Stella AM, De Marco C, Butterfield DA, Calabrese V (2007) Mitochondrial dysfunction, free radical generation and cellular stress response in neurodegenerative disorders. Front Biosci 12:1107–1123
Masoro EJ (2006) Dietary restriction-induced life extension: a broadly based biologica phenomenon. Biogerontology 7:153–155
Mattson MP, Duan W, Guo Z (2003) Meal size and frequency affect neuronal plasticity and vulnerability to disease: cellular and molecular mechanisms. J Neurochem 84:417–431
Migliore L, Coppede F (2008). Environmental-induced oxidative stress in neurodegenerative disorders and aging. Mutat Res 674:73–84
Moore SA, Lopez A, Richardson A, Pahlavani MA (1998) Effect of age and dietary restriction on expression of heat shock protein 70 in rat alveolar macrophages. Mech Ageing Dev 104:59–73
Moreira PI, Honda K, Liu Q, Santos MS, Oliveira CR, Aliev G, Nunomura A, Zhu X, Smith MA, Perry G (2005) Oxidative stress: the old enemy in Alzheimer’s disease pathophysiology. Curr Alzheimer Res 2:403–408
Njemini R, Bautmans I, Lambert M, Demanet C, Mets T (2007) Heat shock proteins and chemokine/cytokine secretion profile in ageing and inflammation. Mech Ageing Dev 128:450–454
Parkash J, Kaur G (2005) Neuronal-glial plasticity in gonadotropin-releasing hormone release in adult female rats: role of the polysialylated form of the neural cell adhesion molecule. J Endocrinol 186:397–409
Radak Z, Takahashi R, Kumiyama A, Nakamoto H, Ohno H, Ookawara T, Goto S (2002) Effect of aging and late onset dietary restriction on antioxidant enzymes and proteasome activities, and protein carbonylation of rat skeletal muscle and tendon. Exp Gerontol 37:1423–1430
Radák Z, Takahashi R, Kumiyama A, Nakamoto H, Ohno H, Ookawara T, Goto S (2002) Effect of aging and late onset dietary restriction on antioxidant enzymes and proteasome activities, and protein carbonylation of rat skeletal muscle and tendon. Exp Gerontol 37:1423–1430
Rattan SIS (2005) Hormetic modulation of aging and longevity by mild heat stress. Dose Response 3:533–546
Rattan SIS (2008) Hormesis in aging. Ageing Res Rev 7:63–78
Roth GS, Mattison JA, Ottinger MA, Chachich ME, Lane MA, Ingram DK (2004) Aging in rhesus monkeys: relevance to human health interventions. Science 305:1423–1426
Rutishauser U (2008) Polysialic acid in the plasticity of the developing and adult vertebrate nervous system. Nat Rev Neurosci 9:26–35
Saija A, Princi P, Pisani A, Lanza M, Scalese M, Aramnejad E, Ceserani R, Costa G (1994) Protective effect of glutathione on kainic acid-induced neuropathological changes in the rat brain. Gen Pharmacol 25:97–102
Sato K, Morimoto K, Suemaru S, Sato T, Yamada N (2000) Increased synapsin I immunoreactivity during long-term potentiation in rat hippocampus. Brain Res 872:219–222
Schmued LC, Hopkins KJ (2000) Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration. Brain Res 874:123–130
Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205
Sharma S, Kaur G (2005) Neuroprotective potential of dietary restriction against kainate-induced excitotoxicity in adult male wistar rats. Brain Res Bull 67:482–491
Sharma S, Kaur G (2007) Intermittent dietary restriction as a practical intervention in aging. Ann N Y Acad Sci 1114:419–427
Sharp FR, Massa SM, Swanson RA (1999) Heat-shock protein protection. Trends Neurosci 22:97–99
Siqueira IR, Fochesatto C, de Andrade A, Santos M, Hagen M, Bello-Klein A, Netto CA (2005) Total antioxidant capacity is impaired in different structures from aged rat brain. Int J Dev Neurosci 23:663–671
Sohal RS, Brunk UT (1992) Mitochondrial production of pro-oxidants and cellular senescence. Mutat Res 275:295–304
Sohal RS, Orr WC (1992) Relationship between antioxidants, prooxidants, and the aging process. Ann N Y Acad Sci 663:74–84
Sohal RS, Sohal BH (1991) Hydrogen peroxide release by mitochondria increases during aging. Mech Ageing Dev 57:187–202
Soti C, Csermely P (2002) Chaperones come of age. Cell Stress Chaperones 7:186–190
Stranahan AM, Khalil D, Gould E (2007) Running induces widespread structural alterations in the hippocampus and entorhinal cortex. Hippocampus 17:1017–1022
Suh JH, Shigeno ET, Morrow JD, Cox B, Rocha AE, Frei B, Hagen TM (2001) Oxidative stress in the aging rat heart is reversed by dietary supplementation with (R)–lipoic acid. FASEB J 15:700–706
Sun Y, Ouyang YB, Xu L, Chow AM, Anderson R, Hecker JG, Giffard RG (2006) The carboxyl-terminal domain of inducible Hsp70 protects from ischemic injury in vivo and in vitro. J Cereb Blood Flow Metab 26:937–950
Suttie AW, Dinse GE, Nyska A, Moser GJ, Goldsworthy TL, Maronpot RR (2005) An Investigation of the effects of late-onset dietary restriction on prostate cancer development in the TRAMP mouse. Toxicol Pathol 33:386–397
Tanaka KF, Ochi N, Hayashi T, Ikeda E, Ikenaka K (2006) Fluoro-Jade: new fluorescent marker of rosenthal fibers. Neurosci Lett 407:127–130
van Praag H, Shubert T, Zhao C, Gage FH (2005) Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 25:8680–8685
Weindruch R, Sohal RS (1997) Caloric intake and aging. N Engl J Med 337:986–994
Yang X, Schadt EE, Wang S, Wang H, Arnold AP, Ingram-Drake L, Drake TA, Lusis AJ (2006) Tissue-specific expression and regulation of sexually dimorphic genes in mice. Genome Res 16:995–1004
Acknowledgments
This grant was funded by Indian Council of Medical Research (ICMR) under National Task Force Project- an initiative on Aging Research. Mr. Sandeep Sharma and Ms. Manpreet Kaur are thankful to the ICMR for research fellowship grant during the course of this study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sharma, S., Singh, R., Kaur, M. et al. Late-onset dietary restriction compensates for age-related increase in oxidative stress and alterations of HSP 70 and synapsin1 protein levels in male Wistar rats. Biogerontology 11, 197–209 (2010). https://doi.org/10.1007/s10522-009-9240-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10522-009-9240-4