Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Association of healthy aging with parental longevity


Various measures incorporated in geriatric assessment have found their way into frailty indices (FIs), which have been used as indicators of survival/mortality and longevity. Our goal is to understand the genetic basis of healthy aging to enhance its evidence base and utility. We constructed a FI as a quantitative measure of healthy aging and examined its characteristics and potential for genetic analyses. Two groups were selected from two separate studies. One group (OLLP for offspring of long-lived parents) consisted of unrelated participants at least one of whose parents was age 90 or older, and the other group of unrelated participants (OSLP for offspring of short-lived parents), both of whose parents died before age 76. FI34 scores were computed from 34 common health variables and compared between the two groups. The FI34 was better correlated than chronological age with mortality. The mean FI34 value of the OSLP was 31 % higher than that of the OLLP (P = 0.0034). The FI34 increased exponentially, at an instantaneous rate that accelerated 2.0 % annually in the OLLP (P = 0.024) and 2.7 % in the OSLP (P < < 0.0001) consequently yielding a 63 % larger accumulation in the latter group (P = 0.0002). The results suggest that accumulation of health deficiencies over the life course is not the same in the two groups, likely due to inheritance related to parental longevity. Consistent with this, sib pairs were significantly correlated regarding FI34 scores, and heritability of the FI34 was estimated to be 0.39. Finally, hierarchical clustering suggests that the OLLP and OSLP differ in their aging patterns. Variation in the FI34 is, in part, due to genetic variation; thus, the FI34 can be a phenotypic measure suitable for genetic analyses of healthy aging.

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

Fig. 1
Fig. 2


  1. Carmelli D, Kelly-Hayes M, Wolf PA, Swan GE, Jack LM, Reed T, Guralnik JM (2000) The contribution of genetic influences to measures of lower-extremity function in older male twins. J Gerontol A Biol Sci Med Sci 55(1):B49–B53

  2. Dato S, Montesanto A, Lagani V, Jeune B, Christensen K, Passarino G (2012) Frailty phenotypes in the elderly based on cluster analysis: a longitudinal study of two Danish cohorts. Evidence for a genetic influence on frailty. Age (Dordr) 34(3):571–582

  3. Edwards DR, Gilbert JR, Jiang L, Gallins PJ, Caywood L, Creason M, Fuzzell D, Knebusch C, Jackson CE, Pericak-Vance MA, Haines JL, Scott WK (2011) Successful aging shows linkage to chromosomes 6, 7, and 14 in the Amish. Ann Hum Genet 75(4):516–528

  4. Finch CE (1990) Longevity, senescence, and the genome. The John D. and Catherine T. MacArthur Foundation series on mental health and development. University of Chicago Press, Chicago

  5. Frederiksen H, Gaist D, Petersen HC, Hjelmborg J, McGue M, Vaupel JW, Christensen K (2002) Hand grip strength: a phenotype suitable for identifying genetic variants affecting mid- and late-life physical functioning. Genet Epidemiol 23(2):110–122

  6. 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(3):M146–M156

  7. Gower JC (1971) A general coefficient of similarity and some of its properties. Biometrics 27:857–874

  8. Gudmundsson H, Gudbjartsson DF, Frigge M, Gulcher JR, Stefansson K (2000) Inheritance of human longevity in Iceland. Eur J Hum Genet 8(10):743–749

  9. Hartl DL (1980) Principles of population genetics. Sinauer Associates, Inc., Sunderland

  10. Herskind AM, McGue M, Holm NV, Sorensen TI, Harvald B, Vaupel JW (1996) The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870–1900. Hum Genet 97(3):319–323

  11. Ho YY, Matteini AM, Beamer B, Fried L, Xue QL, Arking DE, Chakravarti A, Fallin MD, Walston J (2011) Exploring biologically relevant pathways in frailty. J Gerontol A Biol Sci Med Sci 66(9):975–979

  12. Jazwinski SM, Kim S, Dai J, Li L, Bi X, Jiang JC, Arnold J, Batzer MA, Walker JA, Welsh DA, Lefante CM, Volaufova J, Myers L, Su LJ, Hausman DB, Miceli MV, Ravussin E, Poon LW, Cherry KE, Welsch MA (2010) HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging. Aging Cell 9(5):698–708

  13. Kaufman L, Rousseeuw PJ (2005) Finding groups in data: an introduction to cluster analysis. Wiley series in probability and mathematical statistics. Wiley, Hoboken

  14. Kerber RA, O'Brien E, Smith KR, Cawthon RM (2001) Familial excess longevity in Utah genealogies. J Gerontol A Biol Sci Med Sci 56(3):B130–B139

  15. Kulminski A, Ukraintseva SV, Akushevich I, Arbeev KG, Land K, Yashin AI (2007a) Accelerated accumulation of health deficits as a characteristic of aging. Exp Gerontol 42(10):963–970

  16. Kulminski AM, Ukraintseva SV, Akushevich IV, Arbeev KG, Yashin AI (2007b) Cumulative index of health deficiencies as a characteristic of long life. J Am Geriatr Soc 55(6):935–940

  17. Kulminski AM, Ukraintseva SV, Culminskaya IV, Arbeev KG, Land KC, Akushevich L, Yashin AI (2008) Cumulative deficits and physiological indices as predictors of mortality and long life. J Gerontol A Biol Sci Med Sci 63(10):1053–1059

  18. Kulminski AM, Arbeev KG, Culminskaya IV, Ukraintseva SV, Christensen K, Yashin AI (2009) Health-related phenotypes and longevity in Danish twins. J Gerontol A Biol Sci Med Sci 64(1):1–8

  19. Kulminski AM, Arbeev KG, Christensen K, Mayeux R, Newman AB, Province MA, Hadley EC, Rossi W, Perls TT, Elo IT, Yashin AI (2011) Do gender, disability, and morbidity affect aging rate in the LLFS? Application of indices of cumulative deficits. Mech Ageing Dev 132(4):195–201

  20. Matteini AM, Fallin MD, Kammerer CM, Schupf N, Yashin AI, Christensen K, Arbeev KG, Barr G, Mayeux R, Newman AB, Walston JD (2010) Heritability estimates of endophenotypes of long and health life: the Long Life Family Study. J Gerontol A Biol Sci Med Sci 65(12):1375–1379

  21. McClearn GE, Johansson B, Berg S, Pedersen NL, Ahern F, Petrill SA, Plomin R (1997) Substantial genetic influence on cognitive abilities in twins 80 or more years old. Science 276(5318):1560–1563

  22. Mitnitski AB, Mogilner AJ, Rockwood K (2001) Accumulation of deficits as a proxy measure of aging. Sci World J 1:323–336. doi:10.1100/tsw.2001.58

  23. Mitnitski AB, Graham JE, Mogilner AJ, Rockwood K (2002a) Frailty, fitness and late-life mortality in relation to chronological and biological age. BMC Geriatr 2:1

  24. Mitnitski AB, Mogilner AJ, MacKnight C, Rockwood K (2002b) The mortality rate as a function of accumulated deficits in a frailty index. Mech Ageing Dev 123(11):1457–1460

  25. Mitnitski A, Bao L, Rockwood K (2006) Going from bad to worse: a stochastic model of transitions in deficit accumulation, in relation to mortality. Mech Ageing Dev 127(5):490–493

  26. Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155(2):945–959

  27. R (2008) Version R 2.11.1; R Development Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria

  28. Rockwood K, Mitnitski A (2007) Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci 62(7):722–727

  29. Rockwood K, Fox RA, Stolee P, Robertson D, Beattie BL (1994) Frailty in elderly people: an evolving concept. CMAJ 150(4):489–495

  30. Rockwood K, Stadnyk K, MacKnight C, McDowell I, Hebert R, Hogan DB (1999) A brief clinical instrument to classify frailty in elderly people. Lancet 353(9148):205–206

  31. Rockwood K, Andrew M, Mitnitski A (2007) A comparison of two approaches to measuring frailty in elderly people. J Gerontol A Biol Sci Med Sci 62(7):738–743

  32. Roff DA (1997) Evolutionary quantitative genetics. Chapman & Hall, New York

  33. Romeis JC, Heath AC, Xian H, Eisen SA, Scherrer JF, Pedersen NL, Fu Q, Bucholz KK, Goldberg J, Lyons MJ, Waterman B, Tsuang MT, True WR (2005) Heritability of SF-36 among middle-age, middle-class, male–male twins. Med Care 43(11):1147–1154

  34. Rowe JW, Kahn RL (1997) Successful aging. Gerontologist 37(4):433–440

  35. Searle SD, Mitnitski A, Gahbauer EA, Gill TM, Rockwood K (2008) A standard procedure for creating a frailty index. BMC Geriatr 8:24

  36. Yang Y, Lee LC (2010) Dynamics and heterogeneity in the process of human frailty and aging: evidence from the U.S. older adult population. J Gerontol B Psychol Sci Soc Sci 65B(2):246–255

Download references


This study was supported by grants from the National Institute on Aging of the National Institutes of Health (K01AG027905 to SK and P01AG022064 to SMJ), by the Louisiana Board of Regents through the Millennium Trust Health Excellence Fund [HEF(2001–06)-02] (to SMJ), and by the Louisiana Board of Regents RC/EEP Fund through the Tulane-LSU CTRC at LSU Interim University Hospital. We thank the CTRC for nursing services, subject testing, and blood draw, and the core lab support for blood sample processing. We also thank the people of Louisiana for participation in our studies. The corresponding authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Author information

Correspondence to Sangkyu Kim or S. Michal Jazwinski.

Electronic supplementary material

Below is the link to the electronic supplementary material.


(DOC 131 kb)

About this article

Cite this article

Kim, S., Welsh, D.A., Cherry, K.E. et al. Association of healthy aging with parental longevity. AGE 35, 1975–1982 (2013). https://doi.org/10.1007/s11357-012-9472-0

Download citation


  • Frailty
  • Deficits
  • Longevity
  • Aging
  • Heritability
  • Age