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The distribution of cellular turnover in the human body
Abstract
We integrated ubiquity, mass and lifespan of all major cell types to achieve a comprehensive quantitative description of cellular turnover. We found a total cellular mass turnover of 80 ± 20 grams per day, dominated by blood cells and gut epithelial cells. In terms of cell numbers, close to 90% of the (0.33 ± 0.02) × 10 12 cells per day turnover was blood cells.
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“The cell types that build each organ are subject to different turnover rates. Some differentiated cell types can last a lifetime, such as neurons in the brain or cardiomyocytes in the heart. Other differentiated cell types are continuously lost and replenished quickly, such as red blood cells, monocytes and epithelial cells of the skin and intestine2.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [2]
Citations
Cites
Revised Estimates for the Number of Human and Bacteria Cells in the Body
Sender, R., Fuchs, S., & Milo, R. (2016) · PLOS Biology · doi:10.1371/journal.pbio.1002533 · Cited by 5,425
Self-citationA Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing
Landgraf, P., Rusu, M., Sheridan, R., Sewer, A., Iovino, N., Aravin, A., Pfeffer, S., Rice, A., Kamphorst, A. O., Landthaler, M., et al. (2007) · Cell · doi:10.1016/j.cell.2007.04.040 · Cited by 3,626
The expensive-tissue hypothesis: The brain and the digestive system in human and primate evolution
Aiello, L. C., & Wheeler, P. (1995) · Current Anthropology · doi:10.1086/204350 · Cited by 2,291
Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans
Sender, R., Fuchs, S., & Milo, R. (2016) · Cell · doi:10.1016/j.cell.2016.01.013 · Cited by 2,050
Self-citationBasic anatomical and physiological data for use in radiological protection: reference values
Valentin, J. (2002) · Annals of the ICRP · doi:10.1016/s0146-6453(03)00002-2 · Cited by 2,024
Variation in cancer risk among tissues can be explained by the number of stem cell divisions
Tomasetti, C., & Vogelstein, B. (2015) · Science · doi:10.1126/science.1260825 · Cited by 1,927
Report of the task group on reference man
(1979) · Annals of the ICRP · doi:10.1016/0146-6453(79)90123-4 · Cited by 1,715
Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products
Colotta, F., Re, F., Polentarutti, N., Sozzani, S., & Mantovani, A. (1992) · Blood · doi:10.1182/blood.v80.8.2012.2012 · Cited by 1,165
An estimation of the number of cells in the human body
Bianconi, E., Piovesan, A., Facchin, F., Beraudi, A., Casadei, R., Frabetti, F., Vitale, L., Pelleri, M. C., Tassani, S., Piva, F., et al. (2013) · Annals of Human Biology · doi:10.3109/03014460.2013.807878 · Cited by 1,012
In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days
Pillay, J., den Braber, I., Vrisekoop, N., Kwast, L. M., de Boer, R. J., Borghans, J. A. M., Tesselaar, K., & Koenderman, L. (2010) · Blood · doi:10.1182/blood-2010-01-259028 · Cited by 873
Origins, structures, and functions of circulating DNA in oncology
Thierry, A. R., El Messaoudi, S., Gahan, P. B., Anker, P., & Stroun, M. (2016) · Cancer and Metastasis Reviews · doi:10.1007/s10555-016-9629-x · Cited by 818
Cell number and cell characteristics of the normal human lung.
Crapo, J. D., Barry, B. E., Gehr, P., Bachofen, M., & Weibel, E. R. (1982) · PubMed · doi:10.1164/arrd.1982.125.6.740 · Cited by 730
RAFF, M. C. (1998) · Nature · doi:10.1038/24055 · Cited by 690
Retrospective Birth Dating of Cells in Humans
Spalding, K. L., Bhardwaj, R. D., Buchholz, B. A., Druid, H., & Frisén, J. (2005) · Cell · doi:10.1016/j.cell.2005.04.028 · Cited by 649
The bioenergetic costs of a gene
Lynch, M., & Marinov, G. K. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1514974112 · Cited by 600
Allometric Relationships of Cell Numbers and Size in the Mammalian Lung
Stone, K. C., Mercer, R. R., Gehr, P., Stockstill, B. L., & Crapo, J. D. (1992) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb/6.2.235 · Cited by 550
THE MICROBIAL CONTRIBUTION TO HUMAN FAECAL MASS
Stephen, A. M., & Cummings, J. H. (1980) · Journal of Medical Microbiology · doi:10.1099/00222615-13-1-45 · Cited by 545
Fecal weight, colon cancer risk, and dietary intake of nonstarch polysaccharides (dietary fiber)
Cummings, J. H., Bingham, S. A., Heaton, K. W., & Eastwood, M. A. (1992) · Gastroenterology · doi:10.1016/0016-5085(92)91435-7 · Cited by 462
Growth dynamics of gut microbiota in health and disease inferred from single metagenomic samples
Korem, T., Zeevi, D., Suez, J., Weinberger, A., Avnit-Sagi, T., Lotan‐Pompan, M., Matot, E., Jona, G., Harmelin, A., Cohen, N., et al. (2015) · Science · doi:10.1126/science.aac4812 · Cited by 445
Measurement of bacterial replication rates in microbial communities
Brown, C. T., Olm, M. R., Thomas, B. C., & Banfield, J. F. (2016) · Nature Biotechnology · doi:10.1038/nbt.3704 · Cited by 384
The distribution of bacterial doubling times in the wild
Gibson, B., Wilson, D. J., Feil, E. J., & Eyre‐Walker, A. (2018) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2018.0789 · Cited by 312
Lahoz-Beneytez, J., Elemans, M., Zhang, Y., Ahmed, R., Salam, A., Block, M., Niederalt, C., Asquith, B., & Macallan, D. C. (2016) · Blood · doi:10.1182/blood-2016-03-700336 · Cited by 300
What's your age again? Determination of human neutrophil half-lives revisited
Tak, T., Tesselaar, K., Pillay, J., Borghans, J. A. M., & Koenderman, L. (2013) · Journal of Leukocyte Biology · doi:10.1189/jlb.1112571 · Cited by 294
Estimated lean body mass as an index for normalization of body fluid volumes in humans
de Boer, P. (1984) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1984.247.4.f632 · Cited by 280
Distribution of lymphocyte subsets and natural killer cells in the human body
Westermann, J., & Pabst, R. (1992) · Journal of Molecular Medicine · doi:10.1007/bf00184787 · Cited by 252
Measurement of Red Cell Lifespan and Aging
Franco, R. S. (2012) · Transfusion Medicine and Hemotherapy · doi:10.1159/000342232 · Cited by 236
Number and distribution of lymphocytes in man. A critical analysis
Trepel, F. (1974) · Journal of Molecular Medicine · doi:10.1007/bf01468720 · Cited by 232
Lynnerup, N., Kjeldsen, H., Heegaard, S., Jacobsen, C., & Heinemeier, J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001529 · Cited by 224
Meta-Analysis of the Turnover of Intestinal Epithelia in Preclinical Animal Species and Humans
Darwich, A. S., Aslam, U., Ashcroft, D. M., & Rostami‐Hodjegan, A. (2014) · Drug Metabolism and Disposition · doi:10.1124/dmd.114.058404 · Cited by 220
Cell death in health and disease
Lockshin, R. A., & Zakeri, Z. F. (2007) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2007.00150.x · Cited by 199
Macallan, D. C., Fullerton, C. A., Neese, R. A., Haddock, K., Park, S. S., & Hellerstein, M. K. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.2.708 · Cited by 190
Relationship of resting metabolic rate to body composition and protein turnover
Welle, S. L., & Nair, K. S. (1990) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1990.258.6.e990 · Cited by 185
Cell Kinetic Basis for Pathophysiology of Psoriasis
Weinstein, G. D., McCullough, J. L., & Ross, P. A. (1985) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12283594 · Cited by 175
Delgado, F. F., Cermak, N., Hecht, V. C., Son, S., Li, Y., Knudsen, S. M., Olçum, S., Higgins, J. M., Chen, J., Grover, W. H., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067590 · Cited by 169
Phenotypic and Genotypic Characteristics of Mastocytosis According to the Age of Onset
Lanternier, F., Cohen-Akenine, A., Palmérini, F., Féger, F., Yang, Y., Zermati, Y., Barète, S., Sans, B., Baude, C., Ghez, D., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001906 · Cited by 167
Metabolic Connections during Apoptotic Cell Engulfment
Han, C. Z., & Ravichandran, K. S. (2011) · Cell · doi:10.1016/j.cell.2011.12.006 · Cited by 149
The Organization of Human Epidermis: Functional Epidermal Units and Phi Proportionality
Hoath, S. B., & Leahy, D. G. (2003) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2003.12606.x · Cited by 148
Volume and osmotic properties of human neutrophils
Ting‐Beall, H. P., Needham, D., & Hochmuth, R. M. (1993) · Blood · doi:10.1182/blood.v81.10.2774.2774 · Cited by 148
Volume and osmotic properties of human neutrophils
Ting‐Beall, H. P., Needham, D., & Hochmuth, R. M. (1993) · Blood · doi:10.1182/blood.v81.10.2774.bloodjournal81102774 · Cited by 144
The ATP Costs and Time Required to Degrade Ubiquitinated Proteins by the 26 S Proteasome
Peth, A., Nathan, J. A., & Goldberg, A. L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.482570 · Cited by 140
The Life Span of Red Cells in the Rat and the Mouse as Determined by Labeling with DFP32 in Vivo
Putten, L. M. V., & Croon, F. (1958) · Blood · doi:10.1182/blood.v13.8.789.789 · Cited by 131
Cell production rates in human tissues and tumours and their significance. Part II: clinical data
Rew, D. A., & Wilson, G. D. (2000) · European Journal of Surgical Oncology · doi:10.1053/ejso.1999.0907 · Cited by 131
Red blood cell survival and kinetics during pregnancy
Lurie, S., & Mamet, Y. (2000) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/s0301-2115(00)00290-6 · Cited by 121
Kim, M. H., Granick, J. L., Kwok, C., Walker, N. J., Borjesson, D. L., CURRY, F. E., Miller, L. S., & Simon, S. I. (2011) · Blood · doi:10.1182/blood-2010-07-296970 · Cited by 120
Body cell mass: model development and validation at the cellular level of body composition
Wang, Z., St‐Onge, M., Beatriz Lecumberri, S., Pi-Sunyer, X., Heshka, S., Wang, J., Kotler, D. P., Gallagher, D., Wielopolski, L., Pierson, R. N., et al. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00227.2003 · Cited by 104
Tomasetti, C., Poling, J., Roberts, N. J., London, N. R., Pittman, M. E., Haffner, M. C., Rizzo, A. J., Baras, A. S., Karim, B. O., Kim, A., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1905722116 · Cited by 96
Energy cost of whole-body protein synthesis measured in vivo in chicks
Aoyagi, Y., TASAKI, I., OKUMURA, J., & Muramatsu, T. (1988) · Comparative Biochemistry and Physiology Part A Physiology · doi:10.1016/0300-9629(88)90962-0 · Cited by 90
(2006) · CABI eBooks · doi:10.1079/9780851996134.0000 · Cited by 87
Role of light in human skin color variation
Quevedo, W. C., Fitzpatrick, T. B., Pathak, M. A., & Jimbow, K. (1975) · American Journal of Physical Anthropology · doi:10.1002/ajpa.1330430321 · Cited by 84
Dinant, H. J., & Maat, C. E. M. D. (1978) · British Journal of Haematology · doi:10.1111/j.1365-2141.1978.tb01114.x · Cited by 71
Mascio, M. D., Paik, C. H., Carrasquillo, J. A., Maeng, J., Jang, B., Shin, I. S., Srinivasula, S., Byrum, R., Neria, A., Kopp, W., et al. (2009) · Blood · doi:10.1182/blood-2008-12-192203 · Cited by 58
Age effect on cell-transit time in mouse jejunal epithelium
Fry, R. J., Lesher, S. W., & Kohn, H. I. (1961) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1961.201.1.213 · Cited by 55
Three-dimensional structure of the human small intestinal mucosa in health and disease.
Loehry, C. A., & Creamer, B. (1969) · Gut · doi:10.1136/gut.10.1.6 · Cited by 55
Kuse, R., Schuster, S. J., Sch�bbe, H., Dix, S., & Hausmann, K. (1985) · Annals of Hematology · doi:10.1007/bf00320301 · Cited by 54
Quantitative Histology of the Gastric Mucosa: Man, Dog, Cat, Guinea Pig, and Frog
Hogben, C. A. M., Kent, T. H., Woodward, P. A., & Aj, S. (1974) · Gastroenterology · doi:10.1016/s0016-5085(19)32700-3 · Cited by 53
Borghans, J. A. M., Tesselaar, K., & de Boer, R. J. (2018) · Immunological Reviews · doi:10.1111/imr.12693 · Cited by 53
Models for the red blood cell lifespan
Shrestha, R. P., Horowitz, J., Hollot, C. V., Germain, M. J., Widness, J. A., Mock, D. M., Veng‐Pedersen, P., & Chait, Y. (2016) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-016-9470-4 · Cited by 46
Deuterium and neutrophil kinetics
Li, K. W., Turner, S., Emson, C. L., Hellerstein, M. K., & Dale, D. C. (2011) · Blood · doi:10.1182/blood-2010-12-322271 · Cited by 45
Morphometric analysis of small intestinal mucosa. IV. Determining cell volumes
Crowe, P. T., & Marsh, M. N. (1993) · Virchows Archiv A Pathological Anatomy and Histopathology · doi:10.1007/bf01606454 · Cited by 28
A concept of the pathogenesis of anemia applied to disorders of the intestinal mucosa
Crosby, W. H. (1961) · Digestive Diseases and Sciences · doi:10.1007/bf02231066 · Cited by 21
A mathematical computer simulation model for the development of colonic polyps and colon cancer
Mehl, L. E. (1991) · Journal of Surgical Oncology · doi:10.1002/jso.2930470409 · Cited by 19
Marsh, M. N., Crowe, P. T., Moriarty, K. J., & Ensarı, A. (2003) · Humana Press eBooks · doi:10.1385/1-59259-082-9:125 · Cited by 17
An, G., Widness, J. A., Mock, D. M., & Veng‐Pedersen, P. (2016) · The AAPS Journal · doi:10.1208/s12248-016-9923-0 · Cited by 16
Research works printed but not linked: 3
- Nozick, R. Philosophical Explanations (The Belknap Press, 1981).
- Forte, J. G. in Comprehensive Human Physiology From Cellular Mechanisms to Integration (eds Greger, R. & Windhorst, U.) 1239–1258 (Springer-Verlag, 1996).
- Apostoaei, A. J. & Trabalka, J. R. Review, synthesis and application of information on the human lymphatic system to radiation dosimetry for chronic lymphocitic leukemia. 12–39 (SENES Oak Ridge, Inc. Center for Risk Analysis, 2010).
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Metadata
- Authors
- Sender, R., & Milo, R.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Milo, Ron
- ORCID
- Venue
- Nature Medicine
- Published
- 2021-01
- Volume
- 27
- Issue
- 1
- Pages
- 45-48
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W3120885077
- Cited by
- 420
- References
- 62
- Citations by year
- 2026: 60 · 2025: 79 · 2024: 95 · 2023: 94 · 2022: 69 · 2021: 23
- FWCI
- 24.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel Science Foundation (Grant 740/16)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- cell turnover, cell death, tissue regeneration, blood cells, intestinal epithelial cells, cell lifespan, human body, cell number
- MeSH terms
- Blood Cells, Epithelial Cells, Humans, Cellular Senescence
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