Encyclopedia of Gerontology and Population Aging

Living Edition
| Editors: Danan Gu, Matthew E. Dupre

Biology of Frailty

  • Alice E. Kane
  • Elise S. Bisset
  • Susan E. HowlettEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-69892-2_356-1

Definition

With the aging of the population, frailty has become a critically important area of research. Despite this, there is no universally accepted definition of frailty. Frailty is often considered to be an age-associated decline in functional reserve across numerous physiologic systems, which results in an increased vulnerability to external stressors. Thus, frail older individuals can experience adverse outcomes, including death, in response to even minor stressors. Investigation of the molecular and cellular factors that give rise to frailty, known as the “biology of frailty,” is an emerging field. At present the underlying biology of frailty, and the overlap or distinction from the biology of aging itself, is not well understood.

Overview

The study of the biology of frailty has been facilitated by the development of various instruments that can be used to quantify the level of frailty in an individual. The frailty phenotype and frailty indexare two different tools that are...

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References

  1. Aas SN, Hamarsland H, Cumming KT et al (2019) The impact of age and frailty on skeletal muscle autophagy markers and specific strength: a cross-sectional comparison. Exp Gerontol 9(125):110687.  https://doi.org/10.1016/j.exger.2019.110687CrossRefGoogle Scholar
  2. Andreux PA, van Diemen MPJ, Heezen MR et al (2018) Mitochondrial function is impaired in the skeletal muscle of pre-frail elderly. Sci Report 8:8548.  https://doi.org/10.1038/s41598-018-26944-xCrossRefGoogle Scholar
  3. Andrew MK (2015) Frailty and social vulnerability. Interdiscip Top Gerontol Geriatr 41:186–195.  https://doi.org/10.1159/000381236CrossRefGoogle Scholar
  4. Apóstolo J, Cooke R, Bobrowicz-Campos E et al (2018) Effectiveness of interventions to prevent pre-frailty and frailty progression in older adults: a systematic review. JBI Database System Rev Implement Rep 16(1):140–232.  https://doi.org/10.11124/JBISRIR-2017-003382CrossRefGoogle Scholar
  5. Ashar FN, Moes A, Moore AZ et al (2016) Association of Mitochondrial DNA levels with frailty and all-cause mortality. J Mol Med 93(2):177–186.  https://doi.org/10.1007/s00109-014-1233-3CrossRefGoogle Scholar
  6. Athanasopoulou S, Chondrogianni N, Santoro A et al (2018) Beneficial effects of elderly tailored Mediterranean diet on the proteasomal proteolysis. Front Physiol 9:457.  https://doi.org/10.3389/fphys.2018.00457CrossRefGoogle Scholar
  7. Breitling LP, Saum K, Perna L et al (2016) Frailty is associated with the epigenetic clock but not with telomere length in a German cohort. J Clin Epigenet 8:21.  https://doi.org/10.1186/s13148-016-0186-5CrossRefGoogle Scholar
  8. Erlandson KM, Ng DK, Jacobsen LP (2017) Inflammation, immune activation, Immunosenescence, and hormonal biomarkers in the frailty-related phenotype of men with or at risk for HIV infection. J Infect Dis 215(2):228–237.  https://doi.org/10.1093/infdis/jiw523CrossRefGoogle Scholar
  9. Fried LP, Tangen CM, Walston J et al (2001) Frailty in older adults: evidence for phenotype. J Gerontol 56(3):M146–M157.  https://doi.org/10.1093/gerona/56.3.M146CrossRefGoogle Scholar
  10. Gale CR, Marioni RE, Harris SE et al (2018) DNA methylation and the epigenetic clock in relation to physical frailty in older people: the Lothian birth cohort 1936. Clin Epigenetics 10(1):101.  https://doi.org/10.1186/s13148-018-0538-4CrossRefGoogle Scholar
  11. Horvath S, Raj K (2018) DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet 19(6):371–384.  https://doi.org/10.1038/s41576-018-0004-3CrossRefGoogle Scholar
  12. Howlett SE, Rockwood MR, Mitnitski A et al (2014) Standard laboratory tests to identify older adults at increased risk of death. BMC Med 12:171.  https://doi.org/10.1186/s12916-014-0171-9CrossRefGoogle Scholar
  13. Hubbard R, Woodhouse K (2010) Frailty, inflammation and the elderly. Biogerontology 11(5):635–664.  https://doi.org/10.1007/s10522-010-9292-5CrossRefGoogle Scholar
  14. Kane AE, Howlett SE (2017) Advances in preclinical models of frailty. J Gerontol A Biol Sci Med Sci 72(7):867–869.  https://doi.org/10.1093/gerona/glx072CrossRefGoogle Scholar
  15. Kane AE, Sinclair DA (2019) Frailty biomarkers in humans and rodents: current approaches and future advances. Mech Ageing Dev 180:117–128.  https://doi.org/10.1016/j.mad.2019.03.007CrossRefGoogle Scholar
  16. Kane AE, Hilmer SN, Boyer D et al (2016) Impact of longevity interventions on a validated mouse clinical frailty index. J Gerontol A Biol Sci Med Sci 71(3):333–339.  https://doi.org/10.1093/gerona/glu315CrossRefGoogle Scholar
  17. Kane AE, Keller KM, Heinze-Milne S et al (2019) A murine FI based on clinical and laboratory measurements: links between frailty and pro-inflammatory cytokines differ in a sex-specific manner. J Gerontol A Biol Sci Med Sci 74(3):271–282.  https://doi.org/10.1093/gerona/gly117CrossRefGoogle Scholar
  18. Kumar R, Pradham R, Ambashtha AK (2016) Comparative evaluation of seven isoforms of serum sirtuins as protein marker for frailty. J Protein Proteomic 7(2):101–106.  https://doi.org/10.1111/acel.12260CrossRefGoogle Scholar
  19. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153(6):1194–1121.  https://doi.org/10.1016/j.cell.2013.05.039CrossRefGoogle Scholar
  20. Mitnitski AB, Mogilner AJ, Rockwood K (2001) Accumulation of deficits as a proxy measure of aging. Sci World J 1:323–336.  https://doi.org/10.1100/tsw.2001.58CrossRefGoogle Scholar
  21. Puts MT, Visser M, Twisk JW et al (2005) Endocrine and inflammatory markers as predictors of frailty. Clin Endocrinol 63(4):403–411.  https://doi.org/10.1111/j.1365-2265.2005.02355CrossRefGoogle Scholar
  22. Rockwood K, Blodgett JM, Theou O et al (2017) A frailty index based on deficit accumulation quantifies mortality risk in humans and in mice. Sci Rep 7:43068.  https://doi.org/10.1038/srep43068CrossRefGoogle Scholar
  23. Tompkins B, DiFede D, Khan A et al (2017) Allogeneic mesenchymal stem cells ameliorate aging frailty: a phase II randomized, double-blind, placebo-controlled clinical trial. J Gerontol A Biol Sci Med Sci 72(11):1513–1522.  https://doi.org/10.1093/gerona/glx056CrossRefGoogle Scholar
  24. Valdiglesias V, Sanchez-Flores M, Marcos-Pérez D et al (2018) Exploring genetic outcomes as frailty biomarkers. J Gerontol A Biol Sci Med Sci 74(2):168–175.  https://doi.org/10.1093/gerona/gly085CrossRefGoogle Scholar
  25. Vijg J, Suh Y (2013) Genome instability and aging. Annu Rev Physiol 75:645–668.  https://doi.org/10.1146/annurev-physiol-030212-183715CrossRefGoogle Scholar
  26. Xu M, Tchkonia T, Ding H et al (2015) JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age. PNAS 112(46):E6301–E6310.  https://doi.org/10.1073/pnas.1515386112CrossRefGoogle Scholar
  27. Xu M, Pirtskhalava T, Farr JN et al (2018) Senolytics improve physical function and increase lifespan in old age. Nat Med 24(8):1246–1256.  https://doi.org/10.1038/s41591-018-0092-9CrossRefGoogle Scholar
  28. Zhou J, Wang J, Shen Y et al (2018) The association between telomere length and frailty: a systematic review and meta-analysis. Exp Gerontol 106:16–20.  https://doi.org/10.1016/j.exger.2018.02.030CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Alice E. Kane
    • 1
    • 2
  • Elise S. Bisset
    • 3
  • Susan E. Howlett
    • 3
    • 4
    Email author
  1. 1.Department of GeneticsHarvard Medical SchoolBostonUSA
  2. 2.Charles Perkins CentreUniversity of SydneySydneyAustralia
  3. 3.Department of PharmacologyDalhousie UniversityHalifaxCanada
  4. 4.Department of Medicine (Geriatric Medicine)Dalhousie UniversityHalifaxCanada

Section editors and affiliations

  • Olga Theou
    • 1
  1. 1.Department of MedicineDalhousie UniversityHalifaxCanada