Yong-Han He, Shao-Yan Pu, Wen Li, Xiao-Qiong Chen, Fu-Hui Xiao, Dong-Jing Yan, Yao-Wen Liu, Rong Lin, Xiao-Ping Liao, Xing-Li Yang, Ming-Xia Ge, Wang-Wei Cai, Qing-Peng Kong


Hemoglobin (HGB) in the blood carries oxygen from the lungs to other organs to produce energy. Calorie restriction has been shown to slow aging and extend lifespan. Thus, we hypothesized that HGB may be associated with human longevity as a link to energy metabolism. To test this hypothesis, HGB levels in the blood of 60 centenarian (CEN) families were measured and its association with age (20-80 and 20-100 years) was studied, as well as the associations of CEN HGB with levels in first generation offspring (F1) and their spouses (F1SP). The results showed no association of HGB with age between 20 and 80 years (r=-0.097, p=0.160); however a strikingly inverse relationship with age between 20 and 100 years (r=-0.526, p<0.001) was revealed. After dividing the samples into four age groups (20-39, 40-59, 60-80 and ≥100 years), the HGB in CEN were significantly lower than that of F1SP (p<0.001). Interestingly, the HGB levels of CEN were significantly associated with that of F1 (r=0.379, p=0.015) but not with F1SP (r=0.022, p=0.451), suggesting that HGB could be a heritable phenotype. Furthermore, the genes methylenetetrahydrofolate reductase (MTHFR), nuclear receptor subfamily 2, group C, member 1 (NR2C1) and NR2C2 were differentially expressed in CEN when compared to F1SP, which may likely be responsible for the changes in HGB levels. In conclusion, our results suggest that HGB is a heritable phenotype which associates with familial longevity.


Key words: aging; longevity; hemoglobin; centenarian; energy metabolism


Received: August 13, 2015; Revised: September 30, 2015; Accepted: October 5, 2015; Published online: May 9, 2016

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Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-217.

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

Cutler RG. Peroxide-producing potential of tissues: inverse correlation with longevity of mammalian species. Proc Natl Acad Sci US A. 1985;82(14):4798-802.

Ku HH, Brunk UT, Sohal RS. Relationship between mitochondrial superoxide and hydrogen peroxide production and longevity of mammalian species. Free Rad Biol Med. 1993;15(6):621-7.

Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging. Science. 1996;273(5271):59-63.

Bordone L, Guarente L. Calorie restriction, SIRT1 and metabolism: understanding longevity. Nature reviews Molec Cell Biol. 2005;6(4):298-305.

Verdery RB, Walford RL. Changes in plasma lipids and lipoproteins in humans during a 2-year period of dietary restriction in Biosphere 2. Arch Int Med. 1998;158(8):900-6.

Walford RL, Harris SB, Gunion MW. The calorically restricted low-fat nutrient-dense diet in Biosphere 2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans. Proc Natl Acad Sci USA. 1992;89(23):11533-7.

Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, Salzberg SL, Wold BJ, Pachter L. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 2010;28(5):511-5.

Atzmon G, Barzilai N, Surks MI, Gabriely I. Genetic predisposition to elevated serum thyrotropin is associated with exceptional longevity. J Clin Endocrinol Metabol. 2009;94(12):4768-75.

Hawkins WW, Speck E, Leonard VG. Variation of the hemoglobin level with age and sex. Blood. 1954;9(10):999-1007.

Haslam A, Hausman DB, Johnson MA, Davey A, Poon LW, Allen RH, Stabler SP, Georgia Centenarian S. Prevalence and predictors of anemia in a population-based study of octogenarians and centenarians in Georgia. J Gerontol A-Biol. 2012;67(1):100-6.

Adams KF, Jr., Pina IL, Ghali JK, Wagoner LE, Dunlap SH, Schwartz TA, Stough WG, Mehra MR, Felker GM, Chiong JR, Patterson JH, Kim J, Butler J, Oren RM. Prospective evaluation of the association between hemoglobin concentration and quality of life in patients with heart failure. Am Heart J. 2009;158(6):965-71.

Finkelstein FO, Story K, Firanek C, Mendelssohn D, Barre P, Takano T, Soroka S, Mujais S. Health-related quality of life and hemoglobin levels in chronic kidney disease patients. Clin J Am Soc Nephrol. 2009;4(1):33-8.

Zakai NA, Katz R, Hirsch C, Shlipak MG, Chaves PH, Newman AB, Cushman M. A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: The Cardiovascular Health Study. Arch Int Med. 2005;165(19):2214-20.

Gomez JM, Carrera F. What should the optimal target hemoglobin be? Kidney Int Suppl. 200280):39-43.

Ortuno-Sahagun D, Pallas M, Rojas-Mayorquin AE. Oxidative stress in aging: advances in proteomic approaches. Ox Med Cell Longev. 2014;2014:573208.

Smith JV, Heilbronn LK, Ravussin E. Energy restriction and aging. Curr Op Clin Nutr Metabol Care. 2004;7(6):615-22.

Andersen-Ranberg K, Schroll M, Jeune B. Healthy centenarians do not exist, but autonomous centenarians do: a population-based study of morbidity among Danish centenarians. J Am Geriatric Soc. 2001;49(7):900-8.

Engberg H, Oksuzyan A, Jeune B, Vaupel JW, Christensen K. Centenarians--a useful model for healthy aging? A 29-year follow-up of hospitalizations among 40,000 Danes born in 1905. Aging Cell. 2009;8(3):270-6.

Hitt R, Young-Xu Y, Silver M, Perls T. Centenarians: the older you get, the healthier you have been. Lancet. 1999;354(9179):652.

Haslam A, Hausman DB, Davey A, Elaine Cress M, Johnson MA, Poon LW. Associations between anemia and physical function in Georgia centenarians. J Am Geriatric Soc. 2012;60(12):2362-3.

Fortunato G, Fattoruso O, De Caterina M, Mancini A, Di Fiore R, Alfieri A, Tafuri D, Buono P. RAS and MTHFR gene polymorphisms in a healthy exercise-trained population: association with the MTHFR (TT) genotype and a lower hemoglobin level. Int J Sports Med. 2007;28(2):172-7.

Scherzer TM, Stattermayer AF, Stauber R, Maieron A, Strasser M, Laferl H, Schwarzer R, Datz C, Rutter K, Beinhardt S, Steindl-Munda P, Hofer H, Ferenci P. Effect of gender and ITPA polymorphisms on ribavirin-induced anemia in chronic hepatitis C patients. J Hepatol. 2013;59(5):964-71.

Suzuki F, Suzuki Y, Akuta N, Sezaki H, Hirakawa M, Kawamura Y, Hosaka T, Kobayashi M, Saito S, Arase Y, Ikeda K, Kobayashi M, Chayama K, Kamatani N, Nakamura Y, Miyakawa Y, Kumada H. Influence of ITPA polymorphisms on decreases of hemoglobin during treatment with pegylated interferon, ribavirin, and telaprevir. Hepatology. 2011;53(2):415-21.

Tanabe O, Katsuoka F, Campbell AD, Song W, Yamamoto M, Tanimoto K, Engel JD. An embryonic/fetal beta-type globin gene repressor contains a nuclear receptor TR2/TR4 heterodimer. EMBO J. 2002;21(13):3434-42.


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