Skip to main content
Log in

Late-onset intermittent fasting dietary restriction as a potential intervention to retard age-associated brain function impairments in male rats

  • Published:
AGE Aims and scope Submit manuscript

Abstract

Lifelong dietary restriction (DR) is known to have many potential beneficial effects on brain function as well as delaying the onset of neurological diseases. In the present investigation, the effect of late-onset short-term intermittent fasting dietary restriction (IF-DR) regimen was studied on motor coordination and cognitive ability of ageing male rats. These animals were further used to estimate protein carbonyl content and mitochondrial complex I–IV activity in different regions of brain and peripheral organs, and the degree of age-related impairment and reversion by late-onset short-term IF-DR was compared with their levels in 3-month-old young rats. The results of improvement in motor coordination by rotarod test and cognitive skills by Morris water maze in IF-DR rats were found to be positively correlated with the decline in the oxidative molecular damage to proteins and enhanced mitochondrial complex IV activity in different regions of ageing brain as well as peripheral organs. The work was further extended to study the expression of synaptic plasticity-related proteins, such as synaptophysin, calcineurin and CaM kinase II to explore the molecular basis of IF-DR regimen to improve cognitive function. These results suggest that even late-onset short-term IF-DR regimen have the potential to retard age-associated detrimental effects, such as cognitive and motor performance as well as oxidative molecular damage to proteins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Adams MM, Shi L, Linville MC, Forbes ME, Long AB, Bennett C, Newton IG, Carter CS, Sonntag WE, Riddle D, Brunso-Bechtold JK (2008) Caloric restriction and age affect synaptic proteins in hippocampal CA3 and spatial learning ability. Exp Neurol 211:141–149

    Article  PubMed  CAS  Google Scholar 

  • Ahmet I, Wan R, Mattson MP, Lakatta EG, Talan M (2005) Cardioprotection by intermittent fasting in rats. Circulation 112(20):3115–3121

    Article  PubMed  Google Scholar 

  • Aksenov V, Long J, Lokuge S, Foster JA, Liu J, Rollo CD (2010) Dietary amelioration of locomotor, neurotransmitter and mitochondrial aging. Exp Biol Med 235:66–76

    Article  CAS  Google Scholar 

  • Albers DS, Beal MF (2000) Mitochondrial dysfunction and oxidative stress in aging and neurodegenerative disease. J Neural Transm Suppl 59:133–154

    PubMed  CAS  Google Scholar 

  • Altun M, Bergman E, Edström E, Johnson H, Ulfhake B (2007) Behavioral impairments of the aging rat. Physiol Behav 92(5):911–923

    Article  PubMed  CAS  Google Scholar 

  • Anson RM, Guo Z, de Cabo R, Iyun T, Rios M, Hagepanos A, Ingram DK, Lane MA, Mattson MP (2003) Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci U S A 100(10):6216–6220

    Article  PubMed  CAS  Google Scholar 

  • Ayala V, Naudı A, Sanz A, Caro P, Portero-Otin M, Barja G, Pamplona R (2007) Dietary protein restriction decreases oxidative protein damage, peroxidizability index, and mitochondrial complex I content in rat liver. J Gerontol A Biol sci Med Sci 62:352–360

    Article  PubMed  Google Scholar 

  • Calabrese EJ, Mattson MP (2011) Hormesis provides a generalized quantitative estimate of biological plasticity. J Cell Commun Signal 5(1):25–38

    Article  PubMed  Google Scholar 

  • Cambon K, Hansen SM, Venero C, Herrero AI, Skibo G, Berezin V, Bock E, Sandi C (2004) A synthetic neural cell adhesion molecule mimetic peptide pomotes synaptogenesis, enhances presynaptic function and facilitates memory consolidation. J Neurosci 24:4197–4204

    Article  PubMed  CAS  Google Scholar 

  • Carter SC, Leeuwenburgh C, Daniels M, Foster CT (2009) Influence of calorie restriction on measures of age related cognitive decline: role of increased physical activity. J Gerontol A Biol Sci Med Sci 64:850–859

    Article  PubMed  Google Scholar 

  • Chaudhuri AR, Waal E, Pierce A, Remmen VA, Ward FW, Richardson F (2006) Detection of protein carbonyls in aging liver tissue: a fluorescence-based proteomic approach. Mech Ageing Dev 127:849–861

    Article  PubMed  CAS  Google Scholar 

  • Chevion M, Berenshtein E, Stadtman ER (2000) Human studies related to protein oxidation: protein carbonyl content as a marker of damage. Free Radic Res 33:S99–S108

    PubMed  CAS  Google Scholar 

  • Cremer H, Genevieve C, Carleton A, Gordis C, Vincent JD, Lledo PM (1998) Long term but not short term plasticity at mossy fiber synapses is impaired in neural cell adhesion molecule deficient mice. Proc Natl Acad Sci USA 95:13242–13247

    Article  PubMed  CAS  Google Scholar 

  • Davies AH, Kelly A, Dhanrajan TM, Lynch MA, Rodrıguez JJ, Stewart GM (2003) Synaptophysin immunogold labelling of synapses decreases in dentate gyrus of the hippocampus of aged rats. Brain Res 986:191–195

    Article  PubMed  CAS  Google Scholar 

  • Dineley KT, Hogan D, Zhang WR, Taglialatela G (2007) Acute inhibition of calcineurin restores associative learning and memory in Tg2576 APP transgenic mice. Neurobiol Learn Mem 88:217–224

    Article  PubMed  CAS  Google Scholar 

  • Dityatev A, Dityateva G, Schachner M (2000) Synaptic strength as a function of post versus presynaptic expression of the neural cell adhesion molecule NCAM. Neuron 26:207–217

    Article  PubMed  CAS  Google Scholar 

  • Djordjevic MA, Perovic M, Tesic V, Tanic N, Rakic L, Ruzdijic S, Kanazir S (2010) Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat. Neurochem Int 56(2):250–255

    Article  CAS  Google Scholar 

  • Drapeau E, Mayo W, Aurousseau C, Le Moal M, Piazza PV, Abrous DN (2003) Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis. Proc Natl Acad Sci U S A 100:14385–14390

    Article  PubMed  CAS  Google Scholar 

  • Feuers RJ (1998) The effects of dietary restriction on mitochondrial dysfunction in aging. Ann N Y Acad Sci 854:192–201

    Article  PubMed  CAS  Google Scholar 

  • Filburn CR, Edris W, Tamatani M, Hogue B, Kudryashova I, Hansford RG (1996) Mitochondrial electron transport chain activities and DNA deletions in regions of the rat brain. Mech Ageing Dev 87(1):35–46

    Article  PubMed  CAS  Google Scholar 

  • Forster MJ, Dubey A, Dawson KM, Stutts WA, Lal H, Sohal RS (1996) Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain. Proc Natl Acad Sci USA 93:4765–4769

    Article  PubMed  CAS  Google Scholar 

  • Forster MJ, Sohal BH, Sohal RS (2000) Reversible effects of long-term caloric restriction on protein oxidative damage. J Gerontol A Biol Sci Med Sci 55:B522–B529

    Article  PubMed  CAS  Google Scholar 

  • Giese KP, Fedorov NB, Filipkowski RK, Silva AJ (1998) Autophosphorylation at Thr286 of the alpha calcium-calmodulin kinase II in LTP and learning. Science 279:870–873

    Article  PubMed  CAS  Google Scholar 

  • Goto S (2006) Health span extension by later-life caloric or dietary restriction: a view based on rodent studies. Biogerontology 7:135–138

    Article  PubMed  Google Scholar 

  • Goto S, Takahashi R, Radak Z, Sharma R (2007) Beneficial biochemical outcomes of late-onset dietary restriction in rodents. Ann N Y Acad Sci 1100:431–441

    Article  PubMed  CAS  Google Scholar 

  • Gredilla R, Barja G, Lopez-Torres M (2001a) Effect of short-term caloric restriction on H2O2 production and oxidative DNA damage in rat liver mitochondria and location of the free radical source. J Bioenerg Biomembr 33:279–287

    Article  PubMed  CAS  Google Scholar 

  • Gredilla R, Sanz A, Lopez-Torres M, Barja G (2001b) Calorie restriction decreases mitochondrial free radical generation at complex I and lowers oxidative damage to mitochondrial DNA in the rat heart. FASEB J 15:U481–U496

    Google Scholar 

  • Griffths D (1989) Clarification and extraction. In: Harris ELV, Angal S (eds) Protein purification methods a practical approach. IRL, Oxford, pp 91–97

    Google Scholar 

  • Grune T, Shringarpure R, Sitte N, Davies K (2001) Age-related changes in protein oxidation and proteolysis in mammalian cells. J Gerontol A Biol Sci Med Sci 56A:B459–B467

    Article  CAS  Google Scholar 

  • Hamadeh MJ, Rodriguez MC, Kaczor JJ, Tarnopolsky MA (2005) Caloric restriction transiently improves motor performance but hastens clinical onset of disease in the Cu/Zn-superoxide dismutase mutant G93A mouse. Muscle Nerve 31:214–220

    Article  PubMed  CAS  Google Scholar 

  • Harvie MN, Pegington M, Mattson MP, Frystyk J, Dillon B, Evans G, Cuzick J, Jebb SA, Martin B, Cutler RG, Son TG, Maudsley S, Carlson OD, Egan JM, Flyvbjerg A, Howell A (2011) The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int J Obes 35(5):714–727

    Article  CAS  Google Scholar 

  • Hashimoto T, Watanabe S (2005) Chronic food restriction enhances memory in mice—analysis with matched drive levels. Neuroreport 16:1129–1133

    Article  PubMed  Google Scholar 

  • Hatefi Y, Rieske JS (1967) The preparation and properties of DPNH-cytochrome C reductase (Complex I of respiratory chain). In: Estabrook RW, Pullman ME (eds) Methods in enzymology, vol 10. Academic, New York, pp 235–239

    Google Scholar 

  • Hsu KS, Huang CC, Liang YC, Wu HM, Chen YL, Lo SW, Ho WC (2002) Alterations in the balance of protein kinase and phosphatase activities and age-related impairments of synaptic transmission and long-term potentiation. Hippocampus 12:787–802

    Article  PubMed  CAS  Google Scholar 

  • Hursting SD, Smith SM, Lashinger LM, Harvey AE, Perkins SN (2009) Calories and carcinogenesis: lessons learned from 30 years of calorie restriction research. Carcinogenesis 31:83–89

    Article  PubMed  Google Scholar 

  • Jabr RI, Wilson JA, Riddervold M, Jenkins AH, Perrino BA, Clapp LH (2007) Nuclear translocation of calcineurin Aα but not calcineurin Aβ by platelet-derived growth factor in rat aortic smooth muscle. Am J Physiol Cell Physiol 292:C2213–C2225

    Article  PubMed  CAS  Google Scholar 

  • Jouvenceau A, Dutar P (2006) A role for the protein phosphatase 2B in altered hippocampal synaptic plasticity in the aged rat. J Physiol Paris 99:154–161

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Keenan KP, Coleman JB, McCoy CL, Hoe CM, Soper KA, Laroque P (2000) Chronic nephropathy in ad libitum overfed Sprague–Dawley rats and its early attenuation by increasing degrees of dietary (caloric) restriction to control growth. Toxicol Pathol 28:788–798

    Article  PubMed  CAS  Google Scholar 

  • Keller JN, Schmitt FA, Scheff SW, Ding Q, Chen Q, Butterfield DA, Markesbery WR (2005) Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 64:1152–1156

    Article  PubMed  CAS  Google Scholar 

  • King DL, Arendash GW (2002) Maintained synaptophysin immunoreactivity in Tg2576 transgenic mice during aging: correlations with cognitive impairment. Brain Res 926:58–68

    Article  PubMed  CAS  Google Scholar 

  • Klee CB, Ren H, Wang X (1998) Regulation of the calmodulin-stimulated protein phosphatase, calcineurin. J Biol Chem 273:13367–13370

    Article  PubMed  CAS  Google Scholar 

  • Kumar S, Parkash J, Kataria H, Kaur G (2010) Interactive effect of excitotoxic injury and dietary restriction on neurogenesis and neurotrophic factors in adult male rat brain. Neurosci Res 65:367–374

    Article  Google Scholar 

  • Lemaire V, Koehl M, Le Moal M, Abrous DN (2000) Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc Natl Acad Sci U S A 97:11032–11037

    Article  PubMed  CAS  Google Scholar 

  • Lesne S, Koh MT, Kotilinek L, Kayed R (2006) A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440:352–357

    Article  PubMed  CAS  Google Scholar 

  • Levine RL, Garland D, Oliver CN et al (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186:464–478

    Article  PubMed  CAS  Google Scholar 

  • Lin SJ, Defossez PA, Guarente L (2000) Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289:2126–2128

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Fiskum G, Schubert D (2002) Generation of reactive oxygen species by the mitochondrial electron transport chain. J Neurochem 80:780–787

    Article  PubMed  CAS  Google Scholar 

  • Liu HX, Zhang JJ, Zheng P, Zhang Y (2005) Altered expression of MAP-2, GAP-43, and synaptophysin in the hippocampus of rats with chronic cerebral hypoperfusion correlates with cognitive impairment. Brain Res Mol Brain Res 139:169–177

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Torres M, Gredilla R, Sanz A, Barja G (2002) Influence of aging and long-term caloric restriction on oxygen radical generation and oxidative DNA damage in rat liver mitochondria. Free Rad Biol and Med 32:882–889

    Article  CAS  Google Scholar 

  • Love R (2005) Calorie restriction may be neuroprotective in AD and PD. Lancet Neurol 4:84

    Article  PubMed  Google Scholar 

  • Mansuy MI (2003) Calcineurin in memory and bidirectional plasticity. Biochem Biophys Res Commun 311:1195–1208

    Article  PubMed  CAS  Google Scholar 

  • Markowska AL, Savonenko A (2002) Retardation of cognitive aging by life-long diet restriction: implications for genetic variance. Neurobiol Aging 23:75–86

    Article  PubMed  Google Scholar 

  • Martin B, Mattson MP, Maudsley S (2006) Caloric restriction and intermittent fasting: two potential diets for successful brain aging. Ageing Res Rev 5(3):332–353

    Article  PubMed  CAS  Google Scholar 

  • Maswood N, Young J, Tilmont E, Zhang Z, Gash DM, Gerhardt GA, Grondin R, Roth GS, Mattison J, Lane MA, Carson RE, Cohen RM, Mouton PR, Quigley C, Mattson MP, Ingram DK (2004) Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson's disease. Proc Natl Acad Sci USA 101:17887–17888

    Article  Google Scholar 

  • Mattson MP (2003) Gene–diet interactions in brain aging and neurodegenerative disorders. Ann Intern Med 139:441–444

    PubMed  CAS  Google Scholar 

  • Mattson MP (2008) Dietary factors, hormesis and health. Ageing Res Rev 7(1):43–48

    Article  PubMed  Google Scholar 

  • Mattson MP (2010) The impact of dietary energy intake on cognitive aging. Front Aging Neurosci 2:1–12

    Google Scholar 

  • Mattson MP, Pedersen WA, Duan W, Culmsee C, Camandola S (1999) Cellular and molecular mechanisms underlying perturbed energy metabolism and neuronal degeneration in Alzheimer's and Parkinson's diseases. Ann N Y Acad Sci 893:154–175

    Article  PubMed  CAS  Google Scholar 

  • Monville C, Torres ME, Dunnett BS (2006) Comparison of incremental and accelerating protocols of the rotarod test for the assessment of motor deficits in the 6-OHDA model. J Neurosci Methods 158:219–223

    Article  PubMed  Google Scholar 

  • Navarro A, Gomez C, Lopez-Cepero MJ, Boveris A (2004) Beneficial effects of moderate exercise on mice aging: survival, behavior, oxidative stress and mitochondrial electron transfer. Am J Physiol Regul Integr Comp Physiol 286:R505–R511

    Article  PubMed  CAS  Google Scholar 

  • Navarro A, Gomez C, Sanchez-Pino MJ, Gonzalez H, Bandez MJ, Boveris AD, Boveris A (2005) Vitamin E at high doses improves survival, neurological performance, and brain mitochondrial function in aging male mice. Am J Physiol Regul Integr Comp Physiol 289:R1329–R1399

    Article  Google Scholar 

  • Navarro A, Lopez-Cepero JM, Bandez MJ, Sanchez-Pino MJ, Gomez C, Cadenas E, Boveris A (2008) Hippocampal mitochondrial dysfunction in rat aging. Am J Physiol Regul Integr Comp Physiol 294:R501–R509

    Article  PubMed  CAS  Google Scholar 

  • Okada M, Nakanishi H, Amamoto T, Urae R, Ando S, Yazawa K, Fujiwara M (2003) How does prolonged caloric restriction ameliorate age-related impairment of long-term potentiation in the hippocampus? Brain Res Mol Brain Res 111:175–181

    Article  PubMed  CAS  Google Scholar 

  • Olgun A, Akman S, Serdar AM, Kutluay T (2002) Oxidative phosphorylation enzyme complexes in caloric restriction. Exp Gerontol 37:639–645

    Article  PubMed  CAS  Google Scholar 

  • Pandya JD, Pauly JR, Nukala VN, Sebastian AH, Day KM, Korde AS, Maragos WF, Hall ED, Sullivan PG (2007) Post injury administration of mitochondrial uncouplers increases tissue sparing and improves behavioral outcome following traumatic brain injury in rodents. J Neurotrauma 24:798–811

    Article  PubMed  Google Scholar 

  • Pathan AR, Viswanad B, Sonkusare SK, Ramarao P (2006) Chronic administration of pioglitazone attenuates intracerebroventricular streptozotocin induced-memory impairment in rats. Life Sci 79(23):2209–2216

    Article  PubMed  CAS  Google Scholar 

  • Rieske JS (1967) Preparation and properties of reduced coenzyme Q cytochrome C reductase (complex III of the respiratory brain). In: Estabrook RW, Pullman ME (eds) Methods in Enzymology, vol 10. Academic Press, New York, pp 239–245

    Google Scholar 

  • Ripple MJ, Verweij M, Brand K, van de Ven M, Goemaere N, van den Engel S, Chu T, Forrer F, Müller C, de Jong M, van IJcken W, IJzermans JN, Hoeijmakers JH, de Bruin RW (2009) Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in mice. Aging Cell 9:40–53

    Google Scholar 

  • Roth GS, Lane MA, Ingram DK, Mattison JA, Elahi D, Tobin JD, Muller D, Metter EJ (2002) Biomarkers of caloric restriction may predict longevity in humans. Science 297:811

    Article  PubMed  CAS  Google Scholar 

  • Rutten BP, Vander Kolk NM, Zandvoort V, Bayer MA, Steinbusch TA, Schmitz C (2005) Age-related loss of synaptophysin immunoreactive presynaptic boutons within the hippocampus of APP751SL, PS1M146L, and APP751SL/PS1M146L transgenic mice. Am J Pathol 167:161–173

    Article  PubMed  CAS  Google Scholar 

  • Sandhu SK, Kaur G (2002) Alterations in oxidative stress scavenger system in aging rat brain and lymphocytes. Biogeronotology 3(3):161–173

    Article  CAS  Google Scholar 

  • Sandhu SK, Kaur G (2003) Mitochondrial electron transport chain complexes in aging rat brain and lymphocytes. Biogerontology 4:19–29

    Article  PubMed  CAS  Google Scholar 

  • Scheff SW, Price DA, Hicks RR, Baldwin SA, Robinson S, Brackney C (2005) Synaptogenesis in the hippocampal CA1 field following traumatic brain injury. J Neurotrauma 22:719–732

    Article  PubMed  CAS  Google Scholar 

  • Sharma S, Singh R, Kaur M, Kaur G (2010) 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

    Article  PubMed  CAS  Google Scholar 

  • Soderling TR (1993) Calcium/calmodulin-dependent protein kinase II: role in learning and memory. Mol Cell Biochem 127–128:93–101

    Article  PubMed  Google Scholar 

  • Toescu EC, Verkhratsky A, Landfield PW (2004) Ca2+ regulation and gene expression in normal brain aging. Trends Neurosci 27:614–620

    Article  PubMed  CAS  Google Scholar 

  • Wang P, Wang WP, Sun-Zhang WHX, Yan-Lou FYH (2008) Impaired spatial learning related with decreased expression of calcium/calmodulin-dependent protein kinase IIα and cAMP-response element binding protein in the pentylenetetrazol-kindled rats. Brain Res 1238:108–117

    Article  PubMed  CAS  Google Scholar 

  • Weindruch R (1996) The retardation of aging by caloric restriction: studies in rodents and primates. Toxicol Pathol 24:742–745

    Article  PubMed  CAS  Google Scholar 

  • Wharton DC, Tzagoloff A (1967) Cytochrome oxidase from beef heart mitochondria. Methods Enzymol 10:245–250

    Article  CAS  Google Scholar 

  • Witte AV, Fobker M, Gellner R, Knecht S, Floela A (2009) Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci USA 106:1255–1260

    Article  PubMed  CAS  Google Scholar 

  • Wu A, Ying Z, Gomez-Pinnilla F (2006) Dietary curcumin counteracts the outcome of tramatic brain injury on oxidative stress, synaptic plasticity and cognition. Exp Neurol 197:309–317

    Article  PubMed  CAS  Google Scholar 

  • Yanai S, Okaichi Y, Okaichi H (2004) Long-term dietary restriction causes negative effects on cognitive functions in rats. Neurobiol Aging 25(3):325–332

    Article  PubMed  Google Scholar 

  • Yonetani T (1967) Cytochrome oxidase: beef heart. In: Estabrook RW, Pullman ME (eds) Methods in enzymology, vol 10. Academic, New York, pp 332–335

    Google Scholar 

  • Zainal TA, Oberley TD, Allison DB, Szweda LI, Weindruch R (2000) Caloric restriction of rhesus monkeys lowers oxidative damage in skeletal muscle. FASEB J 14:1825–1836

    Article  PubMed  CAS  Google Scholar 

  • Ziegler D, Rieske JS (1967) Preparation and properties of succinate dehydrogenase coenzyme Q reductase (complex II). In: Estabrook RW, Pullman ME (eds) Methods in enzymology, vol 10. Academic, New York, pp 231–235

    Google Scholar 

Download references

Acknowledgements

This grant was funded by Indian Council of Medical Research (ICMR) under the National Task Force Project—an initiative on ageing research. Rumani Singh and Sandeep Sharma are thankful to ICMR for the research fellowship grant during entire course of study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gurcharan Kaur.

About this article

Cite this article

Singh, R., Lakhanpal, D., Kumar, S. et al. Late-onset intermittent fasting dietary restriction as a potential intervention to retard age-associated brain function impairments in male rats. AGE 34, 917–933 (2012). https://doi.org/10.1007/s11357-011-9289-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-011-9289-2

Keywords

Navigation