Skip to main content
SpringerLink
Log in

Rates of erythropoiesis in mammals and their relationship with lifespan and hematopoietic stem cells aging

  • Research Article
  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

Investigations on possible links between hematological parameters and longevity are nearly absent. We tested the hypothesis that a fast rate of erythropoiesis, causing an earlier aging of the hematopoietic stem cells pool, contributes to a shorter lifespan. With this aim, we employed a new quantity, daily produced red blood cells per gram of body mass, as a measure of mass-specific rate of erythropoiesis. We found that among mammals rate of erythropoiesis and maximum lifespan are significantly correlated, independently from mass residuals. This seems to be confirmed also by intra-species comparisons and, although with limited data, by the significant correlation of rate of erythropoiesis and rate of telomere shortening in leukocytes (a proxy for hematopoietic stem cell telomere shortening). In our view, this may give a link of causality between rate of erythropoiesis and maximum lifespan. Further studies could test a similar hypothesis also for other kinds of stem cells.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Abkowitz JL, Catlin SN, McCallie MT, Guttorp P (2002) Evidence that the number of hematopoietic stem cells per animal is conserved in mammals. Blood 100:2665–2667

    Article  CAS  PubMed  Google Scholar 

  • Allsopp RC, Morin GB, Horner JW, DePinho R, Harley CB, Weissman IL (2003) Effect of TERT over-expression on the long-term transplantation capacity of hematopoietic stem cells. Nat Med 9:369–371

    Article  CAS  PubMed  Google Scholar 

  • Arai Y, Martin-Ruiz CM, Takayama M, Abe Y, Takebayashi T, Koyasu S, Suematsu M, Hirose N, von Zglinicki T (2015) Inflammation, but not telomere length, predicts successful ageing at extreme old age: a longitudinal study of semi-supercentenarians. EBioMedicine 2:1549–1558

    Article  PubMed  PubMed Central  Google Scholar 

  • Araya AV, Atwater I, Navia MA, Jeffs S (2000) Evaluation of insulin resistance in two kinds of South American camelids: llamas and alpacas. Comp Med 50:490–494

    CAS  PubMed  Google Scholar 

  • Beerman I, Bock C, Garrison BS, Smith ZD, Gu H, Meissner A, Rossi DJ (2013) Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging. Cell Stem Cell 12:413–425

    Article  CAS  PubMed  Google Scholar 

  • Bernitz JM, Kim HS, MacArthur B, Sieburg H, Moore K (2016) Hematopoietic stem cells count and remember self-renewal divisions. Cell 167:1296–1309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brody S (1945) Bioenergetics and growth, with special reference to the efficiency complex in domestic animals. Reinhold Publishing, New York, NY

    Google Scholar 

  • Burke JD (1954) Blood volume in mammals. Physiol Zool 27:1–21

    Article  Google Scholar 

  • Caswell H (2007) Extrinsic mortality and the evolution of senescence. Trends Ecol Evol 22:173–174

    Article  PubMed  Google Scholar 

  • Chamut S, Yapur J, Black-Decima P (2013) Sickling, cytomorphology and blood parameters in brown brocket deer (Mazama gouazoubira Fischer, 1814). Comp Clin Pathol 23:1007–1012

    Article  CAS  Google Scholar 

  • Chen S, Hu M, Shen M, Wang S, Wang C, Chen F, Tang Y, Wang X, Zeng H, Chen M, Gao J, Wang F, Su Y, Xu Y, Wang J (2018) IGF-1 facilitates thrombopoiesis primarily through Akt activation. Blood 132:210–222

    Article  CAS  PubMed  Google Scholar 

  • Cheshier SH, Morrison SJ, Liao X, Weissman IL (1999) In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. PNAS 96:3120–3125

    Article  CAS  PubMed  Google Scholar 

  • Cohen RM, Smith EP, Arbabi S, Quinn CT, Franco RS (2016) Do red blood cell indices explain racial differences in the relationship between hemoglobin A1c and blood glucose? J Pediatr 176:7–9

    Article  PubMed  PubMed Central  Google Scholar 

  • Cortopassi GA, Wang E (1996) There is substantial agreement among interspecies estimates of DNA repair activity. Mech Ageing Dev 91:211–218

    Article  CAS  PubMed  Google Scholar 

  • Daniali L, Benetos A, Susser E, Kark JD, Labat C, Kimura M, Desai K, Granick M, Aviv A (2013) Telomeres shorten at equivalent rates in somatic tissues of adults. Nat Comm 4:1597

    Article  CAS  Google Scholar 

  • de Haan G, Lazare SS (2018) Aging of hematopoietic stem cells. Blood 131:479–487

    Article  CAS  PubMed  Google Scholar 

  • de Magalhães JP, Costa J, Church GM (2007) An analysis of the relationship between metabolism, developmental schedules, and longevity using phylogenetic independent contrasts. J Gerontol A Biol Sci Med Sci 62:149–160

    Article  PubMed  PubMed Central  Google Scholar 

  • De Meyer T, De Buyzere ML, Langlois M, Rietzschel ER, Cassiman P, De Bacquer D, Van Oostveldt P, De Backer GG, Gillebert TC, Van Criekinge W, Bekaert S, Investigators Asklepios (2008) Lower red blood cell counts in middle-aged subjects with shorter peripheral blood leukocyte telomere length. Aging Cell 7:700–705

    Article  CAS  PubMed  Google Scholar 

  • Dingli D, Pacheco JM (2006) Allometric scaling of the active hematopoietic stem cell pool across mammals. PLoS ONE 1:e2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dingli D, Traulsen A, Pacheco JM (2008) Dynamics of haemopoiesis across mammals. Proc Biol Sci 275:2389–2392

    Article  PubMed  PubMed Central  Google Scholar 

  • Ebaugh FG Jr, Ma Benson (1964) Armadillo hemoglobin characteristics and red cell survival. J Cell Comp Physiol 64:183–192

    Article  CAS  PubMed  Google Scholar 

  • Fletch SM, Robinson GA, Karstad LH (1972) The survival time of DF 32 P-labelled erythrocytes in adult male mink. Can J Comp Med 36:61–63

    CAS  PubMed  PubMed Central  Google Scholar 

  • Freckleton RP (2012) Fast likelihood calculations for comparative analyses. Methods Ecol Evol 3:940–947

    Article  Google Scholar 

  • Fujiwara M, Yonezawa T, Arai T, Yamamoto I, Ohtsuka H (2012) Alterations with age in peripheral blood lymphocyte subpopulations and cytokine synthesis in beagles. Vet Med (Auckl) 3:79–84

    Google Scholar 

  • Geiger H, Denkinger M, Schirmbeck R (2014) Hematopoietic stem cell aging. Curr Opin Immunol 29:86–92

    Article  CAS  PubMed  Google Scholar 

  • Gifford SC, Derganc J, Shevkoplyas SS, Yoshida T, Bitensky MW (2006) A detailed study of time-dependent changes in human red blood cells: from reticulocyte maturation to erythrocyte senescence. Br J Haematol 135:395–404

    Article  PubMed  Google Scholar 

  • Gomes NMV et al (2011) Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination. Aging Cell 10:761–768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hart RW, D’Ambrosio SM, Ng KJ, Modak SP (1979) Longevity, stability and DNA repair. Mech Ageing Dev 9:203–223

    Article  CAS  PubMed  Google Scholar 

  • Hassan YM, Abdel-Wahab MF (1968) Blood volume determination in camels (Camelus dromedarius). Isot Environ Health Stud 4:73

    Google Scholar 

  • Heaton PR, Blount DG, Mann SJ, Devlin P, Koelsch S, Smith BH, Stevenson J, Harper EJ, Rawlings JM (2002) Assessing age-related changes in peripheral blood leukocyte phenotypes in domestic shorthaired cats using flow cytometry. J Nutr 132:1607S–1609S

    Article  CAS  PubMed  Google Scholar 

  • Hirokawa K, Utsuyama M, Goto H, Kuramoto K (1984) Differential rate of age-related decline in immune functions in genetically defined mice with different tumor incidence and life span. Gerontology 30:223–233

    Article  CAS  PubMed  Google Scholar 

  • Ireland JL, McGowan CM, Clegg PD, Chandler KJ, Pinchbeck GL (2012) A survey of health care and disease in geriatric horses aged 30 years or older. Vet J 192:57–64

    Article  PubMed  Google Scholar 

  • ISIS, International Species Information System (2002) Reference ranges for physiological values in captive wildlife. Apple Valley, MN: International Species Information System

  • Ivanov IT (2007) Allometric dependence of the life span of mammal erythrocytes on thermal stability and sphingomyelin content of plasma membranes. Comp Biochem Physiol A 147:876–884

    Article  CAS  Google Scholar 

  • Jacobsen NK (1980) Increases in circulating volumes and cardiac size with growth of White-tailed deer (Odocoileus virginianus). Growth 44:58–72

    CAS  PubMed  Google Scholar 

  • Kallen FC (1960) Plasma and blood volumes in the Little brown bat. Am J Physiol 198:999–1005

    Article  CAS  PubMed  Google Scholar 

  • Kimura M, Gazitt Y, Cao X, Zhao X, Lansdorp PM, Aviv A (2010) Synchrony of telomere length among hematopoietic cells. Exp Hematol 38:854–859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirschner K, Chandra T, Kiselev V, Flores-Santa Cruz D, Macaulay IC, Park HJ, Li J, Kent DG, Kumar R, Pask DC, Hamilton TL, Hemberg M, Reik W, Green AR (2017) Proliferation drives aging-related functional decline in a subpopulation of the hematopoietic stem cell compartment. Cell Rep 19:1503–1511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kucia M, Shin DM, Liu R, Ratajczak J, Bryndza E, Masternak MM, Bartke A, Ratajczak MZ (2011) Reduced number of VSELs in the bone marrow of growth hormone transgenic mice indicates that chronically elevated Igf1 level accelerates age-dependent exhaustion of pluripotent stem cell pool: a novel view on aging. Leukemia 25:1370–1374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kucia M, Masternak M, Liu R, Shin DM, Ratajczak J, Mierzejewska K, Spong A, Kopchick JJ, Bartke A, Ratajczak MZ (2013) The negative effect of prolonged somatotrophic/insulin signaling on an adult bone marrow-residing population of pluripotent very small embryonic-like stem cells (VSELs). Age 35:315–330

    Article  CAS  PubMed  Google Scholar 

  • Kurata M, Suzuki M, Agar NS (1993) Antioxidant systems and erythrocyte life-span in mammals. Comp Biochem Physiol B 106:477–487

    Article  CAS  PubMed  Google Scholar 

  • Kurtz A, Zapf J, Eckardt KU, Clemons G, Froesch ER, Bauer C (1988) Insulin-like growth factor I stimulates erythropoiesis in hypophysectomized rats. PNAS 85:7825–7829

    Article  CAS  PubMed  Google Scholar 

  • Latchney SE, Calvi LM (2017) The aging hematopoietic stem cell niche: phenotypic and functional changes and mechanisms that contribute to hematopoietic aging. Semin Hematol 54:25–32

    Article  PubMed  Google Scholar 

  • Latunde-Dada GO, McKie AT, Simpson RJ (2006) Animal models with enhanced erythropoiesis and iron absorption. BBA 1762:414–423

    CAS  PubMed  Google Scholar 

  • Liang R, Ghaffari S (2016) Advances in understanding the mechanisms of erythropoiesis in homeostasis and disease. Brit J Haematol 174:661–673

    Article  CAS  Google Scholar 

  • Luaces JP, Rossi LF, Aldana Marcos HJ, Merani MS (2011) The rete mirabile of the tail, an effective site for sampling sterile blood from armadillos (Dasypodidae, Xenarthra). Italian J Zool 78:63–69

    Article  Google Scholar 

  • Martens UM, Chavez EA, Poon SSS, Schmoor C, Lansdorp PM (2000) Accumulation of short telomeres in human fibroblasts prior to replicative senescence. Exp Cell Res 256:291–299

    Article  CAS  PubMed  Google Scholar 

  • Martin KH, Stehn RA (1977) Blood and spleen response to isolation and cold stress in little brown bats, Myotis lucifugus. Acta Zool 58:53–59

    Article  Google Scholar 

  • McKenney J, Valeri CR, Mohandas N, Fortier N, Giorgio A, Snyder LM (1990) Decreased in vivo survival of hydrogen peroxide-damaged baboon red blood cells. Blood 76:206–211

    CAS  PubMed  Google Scholar 

  • Milman S, Atzmon G, Huffman DM, Wan J, Crandall JP, Cohen P, Barzilai N (2014) Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity. Aging Cell 13:769–771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neuner B, Lenfers A, Kelsch R, Jäger K, Brüggmann N, van der Harst P, Walter M (2015) Telomere length is not related to established cardiovascular risk factors but does correlate with red and white blood cell counts in a German blood donor population. PLoS ONE 10:e0139308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Page MM, Richardson J, Wiens BE, Tiedtke E, Peters CW, Faure PA, Burness G, Stuart JA (2010) Antioxidant enzyme activities are not broadly correlated with longevity in 14 vertebrate endotherm species. AGE 32:255–270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pawelec G (2003) Immunosenescence and human longevity. Biogerontology 4:167–170

    Article  CAS  PubMed  Google Scholar 

  • Portman OW, Roy Chowdhury J, Roy Chowdhury N, Alexander M, Cornelius CE, Arias IM (1984) A nonhuman primate model of Gilbert’s syndrome. Hepatology 4:175–179

    Article  CAS  PubMed  Google Scholar 

  • Promislow DEL (1991) The evolution of mammalian blood parameters: patterns and their interpretation. Physiol Zool 64:393–431

    Article  Google Scholar 

  • Promislow DEL (1994) DNA repair and the evolution of longevity: a critical analysis. J Theor Biol 170:291–300

    Article  CAS  PubMed  Google Scholar 

  • Ringer RK, Aulerich RJ, Pittman R, Cogger EA (1974) Cardiac output, blood pressure, blood volume, and other cardiovascular parameters in mink. J Anim Sci 38:121–123

    Article  CAS  PubMed  Google Scholar 

  • Röhme D (1981) Evidence for a relationship between longevity of mammalian species and life spans of normal fibroblasts in vitro and erythrocytes in vivo. Proc Natl Acad Sci USA 78:5009–5013

    Article  PubMed  Google Scholar 

  • Rufer N, Brümmendorf TH, Kolvraa S et al (1999) Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood. J Exp Med 190:157–167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seluanov A, Chen Z, Hine C, Sasahara THC, Ribeiro AACM, Catania KC, Presgraves DC, Gorbunova V (2007) Telomerase activity coevolves with body mass not lifespan. Aging Cell 6:45–52

    Article  CAS  PubMed  Google Scholar 

  • Shahani S, Braga-Basaria M, Maggio M, Basaria S (2009) Androgens and erythropoiesis: past and present. J Endocrinol Invest 32:704–716

    Article  CAS  PubMed  Google Scholar 

  • Snyder GK, Weathers WW (1977) Hematology, viscosity, and respiratory functions of whole blood of the lesser mouse deer, Tragulus javanicus. J Appl Physiol 42:673–678

    Article  CAS  PubMed  Google Scholar 

  • Speakman JR (2005) Correlations between physiology and lifespan - two widely ignored problems with comparative studies. Aging Cell 4:167–175

    Article  CAS  PubMed  Google Scholar 

  • Steinberg MH, Benz EJ, Adewoye AH, Ebert BL (2012) Pathobiology of the human erythrocyte and its hemoglobins. In: Hoffman R, Benz EJ, Silberstein L, Heslop H, Weitz J, Anastasi J (eds) Hematology: basic principles and practice, 6th edn. Churchill Livingstone, Oxford, pp 406–417

    Google Scholar 

  • Stier A, Reichert S, Criscuolo F, Bize P (2015) Red blood cells open promising avenues for longitudinal studies of ageing in laboratory, non-model and wild animals. Exp Gerontol 71:118–134

    Article  PubMed  Google Scholar 

  • Tacutu R, Thornton D, Johnson E, Budovsky A, Barardo D, Craig T, Diana E, Lehmann G, Toren D, Wang J, Fraifeld VE, de Magalhães JP (2018) Human ageing genomic resources: new and updated databases. Nucleic Acids Res 46:D1083–D1090

    Article  CAS  PubMed  Google Scholar 

  • Tidwell TR, Søreide K, Hagland HR (2017) aging, metabolism, and cancer development: from Peto’s Paradox to the Warburg effect. Aging Dis 8:662–676

    Article  PubMed  PubMed Central  Google Scholar 

  • Tornquist SJ (2010) Hematology of camelids. In: Weiss DJ, Wardrop KJ (eds) Schalm’s veterinary hematology, 6th edn. Blackwell Publishing, Ames, pp 910–917

    Google Scholar 

  • Totafurno J, Bjerknes M, Cheng H (1987) The crypt cycle. Crypt and villus production in the adult intestinal epithelium. Biophys J 52:279–294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Udroiu I, Sgura A (2017) The phylogeny of the spleen. Q Rev Biol 92:411–443

    Article  Google Scholar 

  • Vácha J, Znojil V (1981) The allometric dependence of the life span of erythrocytes on body weight in mammals. Comp Biochem Physiol A Physiol 69:357–362

    Article  Google Scholar 

  • Valiathan R, Ashman M, Asthana D (2016) Effects of ageing on the immune system: infants to elderly. Scand J Immunol 83:255–266

    Article  CAS  PubMed  Google Scholar 

  • Vera E, Bernardes de Jesus B, Foronda M, Flores JM, Blasco MA (2012) The rate of increase of short telomeres predicts longevity in mammals. Cell Rep 2:732–737

    Article  CAS  PubMed  Google Scholar 

  • Vitale G, Brugts MP, Ogliari G, Castaldi D, Fatti LM, Varewijck AJ, Lamberts SW, Monti D, Bucci L, Cevenini E, Cavagnini F (2012) Low circulating IGF-I bioactivity is associated with human longevity: findings in centenarians’ offspring. Aging (Albany NY) 4:580–589

    Article  CAS  Google Scholar 

  • Voigt CC, Matt F, Michener R, Kunz TH (2003) Low turnover rates of carbon isotopes in tissues of two nectar-feeding bat species. J Exp Biol 206:1419–1427

    Article  PubMed  Google Scholar 

  • Wilson A, Laurenti E, Oser G, van der Wath RC, Blanco-Bose W, Jaworski M, Offner S, Dunant CF, Eshkind L, Bockamp E, Lió P, Macdonald HR, Trumpp A (2008) Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell 135:1118–1129

    Article  CAS  PubMed  Google Scholar 

  • Wolford ST, Schroer RA, Gallo PP, Gohs FX, Brodeck M, Falk HB, Ruhren R (1987) Age-related changes in serum chemistry and hematology values in normal Sprague-Dawley rats. Fundam Appl Toxicol 8:80–88

    Article  CAS  PubMed  Google Scholar 

  • Yagil R, Sod-Moriah UA, Meyerstein N (1974) Dehydration and camel blood. I. Red blood cell survival in the one-humped camel Camelus dromedarius. Am J Physiol 226:298–300

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study received no funding.

Author information

Authors and Affiliations

  1. Dipartimento di Scienze, Università degli Studi Roma Tre, Viale G. Marconi 446, 00146, Rome, Italy

    Ion Udroiu & Antonella Sgura

Authors
  1. Ion Udroiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonella Sgura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ion Udroiu.

Ethics declarations

Conflict of interest

All authors declared that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 199 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Udroiu, I., Sgura, A. Rates of erythropoiesis in mammals and their relationship with lifespan and hematopoietic stem cells aging. Biogerontology 20, 445–456 (2019). https://doi.org/10.1007/s10522-019-09804-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-019-09804-7

Keywords

Search

Navigation