Aging Clinical and Experimental Research

, Volume 23, Issue 2, pp 153–158 | Cite as

Relationship between plasma ghrelin, insulin, leptin, interleukin 6, adiponectin, testosterone and longevity in the Baltimore Longitudinal Study of Aging

  • Sari Stenholm
  • E. Jeffrey Metter
  • George S. Roth
  • Donald K. Ingram
  • Julie A. Mattison
  • Dennis D. Taub
  • Luigi Ferrucci
Short Communication


Background and aims: Caloric restriction (CR) is the most robust and reproducible intervention for slowing aging, and maintaining health and vitality in animals. Previous studies found that CR is associated with changes in specific biomarkers in monkeys that were also associated with reduced risk of mortality in healthy men. In this study we examine the association between other potential biomarkers related to CR and extended lifespan in healthy humans. Methods: Based on the Baltimore Longitudinal Study of Aging, “long-lived” participants who survived to at least 90 years of age (n=41, cases) were compared with “short-lived” participants who died between 72–76 yrs of age (n=31, controls) in the nested case control study. Circulating levels of ghrelin, insulin, leptin, interleukin 6, adiponectin and testosterone were measured from samples collected between the ages 58 to 70 yrs. Baseline differences between groups were examined with t-test or Wilcoxon test, and mixed effects general linear model was used for a logistic model to differentiate the two groups with multiple measurements on some subjects. Results: At the time of biomarkers evaluation (58–70 yrs), none of the single biomarker levels was significantly different between the two groups. However, after combining information from multiple biomarkers by adding the z-transformed values, the global score differentiated the long- and short-lived participants (p=0.05). Conclusions: In their sixties, long-lived and short-lived individuals do not differ in biomarkers that have been associated with CR in animals. However, difference between the groups was only obtained when multiple biomarker dysregulation was considered.

Key words

Aging biomarkers caloric restriction longevity 


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  1. 1.
    Weindruch R, Walford RL, Fligiel S, Guthrie D. The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J Nutr 1986; 116: 641–54.PubMedGoogle Scholar
  2. 2.
    Mehta LH, Roth GS. Caloric restriction and longevity: the science and the ascetic experience. Ann N Y Acad Sci 2009; 1172: 28–33.PubMedCrossRefGoogle Scholar
  3. 3.
    Kealy R, Lawler D, Ballam J et al. Effects of diet restriction on lifespan and age-related changes in dogs. J Am Vet Med Assoc 2002; 220: 1315–20.PubMedCrossRefGoogle Scholar
  4. 4.
    Pinney D, Stephens D, Pope L. Lifetime effects of winter supplemental feed level and age at first parturition on range beef cows. J Anim Sci 1972; 34: 1067–74.PubMedGoogle Scholar
  5. 5.
    Lane MA, Mattison J, Ingram DK, Roth GS. Caloric restriction and aging in primates: Relevance to humans and possible CR mimetics. Microsc Res Tech 2002; 59: 335–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Colman RJ, Anderson RM, Johnson SC et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 2009; 325: 201–4.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Mattison JA, Lane MA, Roth GS, Ingram DK. Calorie restriction in rhesus monkeys. Exp Gerontol 2003; 38: 35–46.PubMedCrossRefGoogle Scholar
  8. 8.
    Ingram DK, Roth GS, Lane MA et al. The potential for dietary restriction to increase longevity in humans: extrapolation from monkey studies. Biogerontology 2006; 7: 143–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Lane M, Ingram D, Roth G. 2-Deoxy-D-glucose feeding in rats mimics physiological effects of calorie restriction. J Anti Aging Med 1998; 1: 327–37.CrossRefGoogle Scholar
  10. 10.
    Lane MA, Ingram DK, Roth GS. The serious search for an antiaging pill. Sci Am 2002; 287: 36–41.PubMedCrossRefGoogle Scholar
  11. 11.
    Lane MA, Roth GS, Ingram DK. Caloric restriction mimetics: a novel approach for biogerontology. Methods Mol Biol 2007; 371: 143–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Roth GS, Lane MA, Ingram DK et al. Biomarkers of caloric restriction may predict longevity in humans. Science 2002; 297: 811.PubMedCrossRefGoogle Scholar
  13. 13.
    Yang H, Youm YH, Nakata C, Dixit VD. Chronic caloric restriction induces forestomach hypertrophy with enhanced ghrelin levels during aging. Peptides 2007; 28: 1931–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Komatsu T, Chiba T, Yamaza H et al. Effect of leptin on hypothalamic gene expression in calorie-restricted rats. J Gerontol A Biol Sci Med Sci 2006; 61: 890–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Shimokawa I, Higami Y. Leptin signaling and aging: insight from caloric restriction. Mech Ageing Dev 2001; 122: 1511–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Chiba T, Yamaza H, Higami Y, Shimokawa I. Anti-aging effects of caloric restriction: Involvement of neuroendocrine adaptation by peripheral signaling. Microsc Res Tech 2002; 59: 317–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Zhu M, Miura J, Lu LX et al. Circulating adiponectin levels increase in rats on caloric restriction: the potential for insulin sensitization. Exp Gerontol 2004; 39: 1049–59.PubMedCrossRefGoogle Scholar
  18. 18.
    Ershler WB. Interleukin-6: a cytokine for gerontologists. J Am Geriatr Soc 1993; 41: 176–81.PubMedGoogle Scholar
  19. 19.
    Lamberts SW, van den Beld AW, van der Lely AJ. The endocrinology of aging. Science 1997; 278: 419–24.PubMedCrossRefGoogle Scholar
  20. 20.
    Orwoll E, Lambert LC, Marshall LM et al. Endogenous testosterone levels, physical performance, and fall risk in older men. Arch Intern Med 2006; 166: 2124–31.PubMedCrossRefGoogle Scholar
  21. 21.
    Lehtonen A, Huupponen R, Tuomilehto J et al. Serum testosterone but not leptin predicts mortality in elderly men. Age Ageing 2008; 37: 461–4.PubMedCrossRefGoogle Scholar
  22. 22.
    Shock NW, Greulich R, Andres R et al. Normal Human Aging: The Baltimore Longitudinal Study of Aging, 1984. Washington, DC: U.S. Govt. Printing Office, 1984 (NIH Publication 84–2450).Google Scholar
  23. 23.
    Lissner L, Andres R, Muller DC, Shimokata H. Body weight variability in men: metabolic rate, health and longevity. Int J Obes 1990; 14: 373–83.PubMedGoogle Scholar
  24. 24.
    Talbot LA, Metter EJ, Fleg JL. Leisure-time physical activities and their relationship to cardiorespiratory fitness in healthy men and women 18–95 years old. Med Sci Sports Exerc 2000; 32: 417–25.PubMedCrossRefGoogle Scholar
  25. 25.
    Fleg JL, Morrell CH, Bos AG et al. Accelerated longitudinal decline of aerobic capacity in healthy older adults. Circulation 2005; 112: 674–82.PubMedCrossRefGoogle Scholar
  26. 26.
    Ludbrook J, Dudley H. Why permutation tests are superior to t and F Tests in biomedical research. The American Statistician 1998; 52: 127–32.Google Scholar
  27. 27.
    Maggio M, Basaria S, Ble A et al. Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor in older men. J Clin Endocrinol Metab 2006; 91: 345–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Araujo AB, Travison TG, Bhasin S et al. Association between testosterone and estradiol and age-related decline in physical function in a diverse sample of men. J Am Geriatr Soc 2008; 56: 2000–8.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Ferrucci L, Giallauria F, Schlessinger D. Mapping the road to resilience: novel math for the study of frailty. Mech Ageing Dev 2008; 129: 677–9.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Maggio M, Lauretani F, Ceda GP et al. Relationship between low levels of anabolic hormones and 6-year mortality in older men: the aging in the Chianti Area (InCHIANTI) study. Arch Intern Med 2007; 167: 2249–54.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Cappola AR, Xue QL, Fried LP. Multiple hormonal deficiencies in anabolic hormones are found in frail older women: the Women’s Health and Aging studies. J Gerontol A Biol Sci Med Sci 2009; 64: 243–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Gruenewald TL, Seeman TE, Karlamangla AS, Sarkisian CA. Allostatic load and frailty in older adults. J Am Geriatr Soc 2009; 57: 1525–31.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Fried LP, Xue QL, Cappola AR et al. Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. J Gerontol A Biol Sci Med Sci 2009; 64: 1049–57.PubMedCrossRefGoogle Scholar
  34. 34.
    Stenholm S, Maggio M, Lauretani F et al. Anabolic and catabolic biomarkers as predictors of muscle strength decline: the InCHIANTI Study. Rejuvenation Res 2010; 13: 3–11.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Internal Publishing Switzerland 2011

Authors and Affiliations

  • Sari Stenholm
    • 1
    • 2
  • E. Jeffrey Metter
    • 1
  • George S. Roth
    • 3
  • Donald K. Ingram
    • 4
  • Julie A. Mattison
    • 5
  • Dennis D. Taub
    • 6
  • Luigi Ferrucci
    • 1
  1. 1.National Institute on Aging, Clinical Research Branch, Longitudinal Studies SectionHarbor HospitalBaltimoreUSA
  2. 2.National Institute for Health and WelfareTurkuFinland
  3. 3.GeroScience, Inc.PylesvilleUSA
  4. 4.Pennington Biomedical Research Center, Nutritional Neuroscience and Aging LaboratoryLouisiana State University SystemBaton RougeUSA
  5. 5.Laboratory of Experimental Gerontology, NIA Primate Aging StudiesNational Institute on AgingBaltimoreUSA
  6. 6.Laboratory of ImmunologyNational Institute on AgingBaltimoreUSA

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