Skip to main content

Down Regulation of Sirtuins in the Serum of Frail Elderly as Compared to Non-frail Elderly: Promising Diagnostic Protein Marker for Frailty

  • Chapter
  • First Online:
Topics in Biomedical Gerontology
  • 636 Accesses

Abstract

Ageing, the accumulation of damage to molecules, cells and tissues over a lifetime, often leads to frailty and malfunction. The functional decline, disability and frailty are the common conditions of the geriatric syndromes. The syndrome of frailty is complex and still lack of a standard definition. As the exact cause of frailty of older people is not known, it will be a great challenge to develop biomarker that characterize the frailty syndrome and help in clinical diagnosis. This will provide a new ways of defining disability outcomes in epidemiological studies of the elderly. Based on above evidences, this study attempts to devise a new tool and develop sirtuins as a biological marker for frailty in old age. Most recent study has observed the low expression of sirtuin in old age. This study evaluated the sirtuin in frail person and compared with non-frail elderly person. The concentration of SIRT1, SIRT2 and SIRT3 were evaluated by Surface Plasmon resonance technology. In frail elderly the declining level of SIRT1, SIRT2 and SIRT3 were observed as compared to non-frail elderly. The pronounced declining level of sirtuin in frail elderly can provides an opportunity to develop this protein as a predictive marker in early stages of frailty with suitable cut off values.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Anderson NL, Anderson NG (2002) The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomic 1:845–867

    Article  CAS  Google Scholar 

  • Astrom SU, Cline TW, Rine J (2003) The Drosophila melanogaster sir2+ gene is nonessential and has only minor effects on position-effect variegation. Genetics 163:931–937

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bordone L, Cohen D, Robinson A, Motta MC, van Veen E, Czopik A, Steele AD, Crowe H, Marmor S, Luo J, Gu W, Guarente L (2007) SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell 6:759–767

    Article  CAS  PubMed  Google Scholar 

  • Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, Wang Y, Raederstorff D, Morrow JD, Leeuwenburgh C, Allison DB, Saupe KW, Cartee GD, Weindruch R, Prolla TA (2008) A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS ONE e 3:2264

    Article  Google Scholar 

  • Brys K, Vanfleteren JR, Braeckman BP (2007) Testing the rate-of-living/oxidative damage theory of aging in the nematode model Caenorhabditis elegans. Exp Gerontol 42:845–851

    Article  CAS  PubMed  Google Scholar 

  • Ble A, Cherubini A, Volpato S, Bartali B, Walston JD, Windham BG, Bandinelli S, Lauretani F, Guralnik JM, Ferrucci L (2006) Lower plasma vitamin E levels are associated with the frailty syndrome: the In CHIANTI study. JGerontol A BiolSci Med Sci 61:278–283

    Article  Google Scholar 

  • Cornelius E (1972) Increased incidence of lymphomas in thymectomized mice–evidence for an immunological theory of aging. Experientia 28:459

    Article  CAS  PubMed  Google Scholar 

  • Chen D, Steele AD, Lindquist S, Guarente L (2005) Increase in activity during calorie restriction requires SIRT1. Science 310:1641

    Article  CAS  PubMed  Google Scholar 

  • Campisi J (2000) Cancer, aging and cellular senescence. In Vivo 14:183–188

    CAS  PubMed  Google Scholar 

  • Dali-Youcef N, Lagouge M, Froelich S, Koehl C, Schoonjans K, Auwerx J (2007) Sirtuins: the ‘magnificent seven’, function, metabolism and longevity. Ann Med 39:335–345

    Article  CAS  PubMed  Google Scholar 

  • Ferrara N, Rinaldi B, Corbi G (2008) Exercise training promotes SIRT1 activity in aged rats. Rejuvenation Res 11:139–150

    Article  CAS  PubMed  Google Scholar 

  • Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56:146–156

    Article  Google Scholar 

  • Gerschman R, Gilbert DL, Nye SW, Dwyer P, Fenn WO (1954) Oxygen poisoning and xirradiation: a mechanism in common. Science 119:623–626

    Article  CAS  PubMed  Google Scholar 

  • Heemels M-T (2010) Ageing. Nat Insight 464:503–544

    CAS  Google Scholar 

  • Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425:191–196

    Article  CAS  PubMed  Google Scholar 

  • Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11(3):298–300

    Google Scholar 

  • Harikumar KB, Aggarwal BB (2008) Resveratrol: a multitargeted agent for age-associated chronic diseases. Cell Cycle 7:1020–1035

    Article  CAS  PubMed  Google Scholar 

  • Hirani V, Naganathan V, Cumming RG, Blyth F, Le Couteur DG, Handelsman DJ, Waite LM, Seibel MJ (2013) Associations Between Frailty and Serum 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Concentrations in Older Australian Men: The Concord Health and Ageing in Men Project. J Gerontol A BiolSci Med Sci 68:1112–1121

    Article  CAS  Google Scholar 

  • Kaeberlein M, McVey M, Guarente L (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13:2570–2580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin SJ, Defossez PA, Guarente L (2000) Life span extension by calorie restriction in S. cerevisiae requires NAD and SIR2. Science 289:2126–2128

    Article  CAS  PubMed  Google Scholar 

  • Lin SJ, Kaeberlein M, Andalis AA, Sturtz LA, Defossez PA, Culotta VC, Fink GR, Guarente L (2002) Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature 418:344–348

    Article  CAS  PubMed  Google Scholar 

  • Leng S, Chaves P, Koenig K, Walston J (2002) Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study. J Am Geriatr Soc 50:1268–1271

    Article  PubMed  Google Scholar 

  • Leng SX, Cappola AR, Andersen RE, Blackman MR, Koenig K, Blair M, Walston JD (2004) Serum levels of insulin-like growth factor-I (IGF-I) and dehydroepiandrosterone sulfate (DHEA-S), and their relationships with serum interleukin-6, in the geriatric syndrome of frailty. Aging Clin Exp Res 16:153–157

    Article  CAS  PubMed  Google Scholar 

  • Leng SX, Xue QL, Tian J, Walston JD, Fried LP (2007) Inflammation and frailty in older women. J Am Geriatr Soc 55:864–871

    Article  PubMed  Google Scholar 

  • Leng S, Xue Q, Tian J (2009) Association of neutrophil and monocyte counts with frailty in community-dwelling older women. Exp Gerontol 44:511–516

    Article  PubMed  Google Scholar 

  • Rogina B, Helfand SL (2004) Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci USA 101:15998–16003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwer B, Verdin E (2008) Conserved metabolic regulatory functions of sirtuins. Cell Metab 7:104–112

    Article  CAS  PubMed  Google Scholar 

  • Shin-ichiro (2009) SIRT1 and Caloric Restriction: An Insight Into Possible Trade-Offs Between Robustness and Frailty. Imai Curr Opin Clin Nutr Metab Care 12:350–356

    Google Scholar 

  • Taylor WH (1969) Serum enzymes in the diagnosis of disease. Br J Anaesth 41:227–234

    Article  CAS  PubMed  Google Scholar 

  • Thadikkaran L, Siegenthaler MA, Crettaz D, Queloz PA, Schneider P, Tissot JD (2005) Recent advances in blood-related proteomics. Proteomics 5:3019–3034

    Article  CAS  PubMed  Google Scholar 

  • Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410:227–230

    Article  CAS  PubMed  Google Scholar 

  • Van Heemst D (2010) Insulin, IGF-1 and longevity. Aging Disease 1:147–157

    PubMed  PubMed Central  Google Scholar 

  • Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430:686–689

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Tissenbaum HA (2006) Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO. Mech Ageing Dev 127:48–56

    Article  CAS  PubMed  Google Scholar 

  • Wu IC, Shiesh SC, Kuo PH, Lin XZ (2009) High oxidative stress is correlated with frailty in elderly chinese. J Am Geriatr Soc 57:1666–1671

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Authors acknowledge research section of AIIMS for proving financial support for purchasing chemicals.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sharmistha Dey .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media Singapore

About this chapter

Cite this chapter

Dey, S. (2017). Down Regulation of Sirtuins in the Serum of Frail Elderly as Compared to Non-frail Elderly: Promising Diagnostic Protein Marker for Frailty. In: Rath, P., Sharma, R., Prasad, S. (eds) Topics in Biomedical Gerontology. Springer, Singapore. https://doi.org/10.1007/978-981-10-2155-8_3

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-2155-8_3

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-2154-1

  • Online ISBN: 978-981-10-2155-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics