The naked mole rat – An alternative model species for biomedical ageing research

Naked mole rats (Heterocephalus glaber) are hardly mentioned in the list of the most beautiful animals. Nevertheless, they have an extraordinary reproductive system, are resistant to cancer and oxygen deprivation and (healthyly) grow astonishingly old, considering their small body size. What mechanisms underly these enviable skills?

 

Naked mole rats (Heterocephalus glaber) are among the most unusual mammals. Beneath their wrinkled skin lie remarkable traits: these nearly hairless, 30 g rodents are resistant to cancer and low oxygen levels and can live extraordinarily long lives for their size, without an age-related increase in mortality risk. As healthy ageing becomes increasingly important in our ageing society, naked mole rats provide a fascinating example of evolutionary adaptations from which we can learn — and which are worth protecting.

Since 2008, naked mole rats have been kept and successfully bred for research at the Leibniz-IZW. Nearly 400 animals in 12 colonies live in transparent tunnel systems modeled after their natural underground habitat in the Horn of Africa, where they feed on roots and tubers. Our research focuses on their unusual reproduction ^{[publication no. 2, 3, 5, 9, 12, 18, 19, 27, 35, 39]} and physiology ^{[1-11, 13, 15-18, 20-28, 30-31, 33-36, 38, 39]}, especially the mechanisms that enable healthy ageing ^{[1, 14-17, 21-22, 24-26, 29, 32-34, 36, 38]}. Together with collaborators and through several funded projects, we investigate the genetic and molecular basis of their unique adaptations.

 

Photo: Jon Juarez

• We assessed the atmospheric composition of wild naked mole rat burrows for the first time and found it is surprisingly similar to normal air ^[30] despite their extreme hypoxia tolerance. This tolerance likely becomes relevant when all colony members rest together in the nest.
• Naked mole rats live in eusocial colonies of up to 300 individuals, with reproduction monopolized by a queen and one or a few males (pashas) ^{[2, 3, 12, 17, 39]}. Interestingly, queens and pashas live longer than workers, although all individuals can potentially become breeders. To explore the transcriptomic differences underlying this phenomenon (SAW-2012-FLI2), we identified changes in genes related to sexual hormones, energy and fat metabolism, mitochondria, and other ageing-associated pathways ^{[27, 37]}. These may represent potential targets for future therapeutic interventions.
• We also study age-related bone changes, especially in queens with pronounced spinal elongation. Their epiphyseal growth plates close unusually late, between 5 and 10 years of age ^[22], reflecting widespread neoteny across many traits ^{[22, 25–26, 32–33]}. While telomeres shorten with age in humans and mice, they remain stable or even lengthen in naked mole rats ^[25]. Further, naked mole rat mitochondria maintain their structure and function longer than those of rats and mice ^{[11, 13, 20–21, 26, 32–33]}.
• The collection of microbes in the gastrointestinal tract, the intestinal microbiome, is linked to health and life expectancy. We found similarities between the microbiomes of captive and free-ranging naked mole rats, supercentenarians, and the Hadza hunter-gatherers, who are known for a particularly healthy human microbiome ^{[31, 34]}. Alongside work on their immune system ^{[7, 23]} (SAW-2018-DRFZ), we are currently investigating their complex social structure.

1. Holtze S, Templeton AR, Strassmann JE, Koch R and Begall S. (2026). Special issue on “Biology of African mole-rats”: a tribute to Stan Braude. Mammalian Biology, 1-8. https://doi.org/10.1007/s42991-026-00575-6

2. Wetzel M, Braude S, Hofer H, Holtze S, Sicks F, Szafranski K, Hildebrandt TB. (2026). Rare cases of plural breeding in captive and wild naked mole-rats: insights into social and reproductive dynamics. Mammalian Biology. 106(2):345-64. https://doi.org/10.1007/s42991-025-00538-3

3. Wetzel M, Holtze S, Hofer H and Hildebrandt TB. (2026). Context-dependent vaginal perforation in subordinate female naked mole-rats (Heterocephalus glaber): insights into reproductive plasticity and social modulation. Mammalian Biology, pp.1-14. https://doi.org/10.1007/s42991-025-00520-z

4. Geltinger F, Holtze S, Hildebrandt TB, Ochs M, Brandenberger C (2025): Stereological analysis of the naked mole-rat Heterocephalus glaber provides evidence of altered surfactant function and late alveolarization. Am J Physiol Lung Cell Mol Physiol. 2025 Jul 1;329(1):L84-L96. https://doi:10.1152/ajplung.00246.2024

5. Simone R, Čižmár D, Holtze S, Michel G, Sporbert A, Okolo C, Hildebrandt TB (2023). First in vitro obtained naked mole-rats’ blastocysts from oocytes in vitro matured and piezo-ICSI fertilized. Scientific Reports 13:22355. https://doi.org/10.1038/s41598-023-49661-6

6. Martinez Q, Okrouhlík J, Šumbera R Wright M, Araújo R, Braude S, Hildebrandt TB, Holtze S, Ruf I & Fabre P-H. (2023). Mammalian maxilloturbinal evolution does not reflect thermal biology. Nat Commun 14, 4425. https://doi.org/10.1038/s41467-023-39994-1

7. Gorshkova EA, Gubernatorova EO, Dvorianinova EM, Yurakova TR, Marey MV, Averina OA., Holtze S, Hildebrandt TB, ... & Nedospasov, S. A. (2023). Macrophages from naked mole-rat possess distinct immunometabolic signatures upon polarization. Frontiers in Immunology, 14, 1172467. https://doi.org/10.3389/fimmu.2023.1172467

8. Gerhardt P, Begall S, Frädrich C., Renko K, Hildebrandt TB, Holtze S, Heinrich A, Sahm A, Xheni M, Köhrle J, Rijntjes E, Henning Y. (2023). Comparative analysis of thyroid hormone systems in rodents with subterranean lifestyle. Scientific Reports, 13, 3122. https://doi.org/10.1038/s41598-023-30179-w

9. Wetzel M, Courtiol A, Hofer H, Holtze S, Hildebrandt TB. (2023). Pup Recruitment in a Eusocial Mammal—Which Factors Influence Early Pup Survival in Naked Mole-Rats?. Animals, 13, 630. https://doi.org/10.3390/ani13040630

10. Braude S, Holtze S, Bennett NC, Begall S. (2022). Editorial: Recent advances in the ecology and evolution of the Bathyergidae. Front. Ecol. Evol. 10:1017185. https://doi.org/10.3389/fevo.2022.1017185

11. Vays V, Vangely I, Eldarov C, Popkov V, Holtze S, Hildebrandt T, Averina OA, Bakeeva L, Zorov D. (2022). Unique features of the tissue structure in the naked mole rat (Heterocephalus glaber): hypertrophy of the endoplasmic reticulum and spatial mitochondrial rearrangements in hepatocytes. Int. J. Mol. Sci. 23, 9067, 1-15. https://doi.org/10.3390/ijms23169067

12. Szafranski K, Wetzel M, Holtze S, Büntjen I, Lieckfeldt D, Ludwig A, Huse K, Platzer M, Hildebrandt TB. (2022). The mating pattern of captive naked mole-rats is best described by a monogamy model. Frontiers Ecology and Evolution 10, 1-9. https://doi.org/10.3389/fevo.2022.855688

13. Vays V, Vangely I, Eldarov C, Holtze S, Hildebrandt T, Bakeeva L, Skulachev V. (2021). Progressive reorganization of mitochondrial apparatus in aging skeletal muscle of naked mole rats (Heterocephalus glaber) as revealed by electron microscopy: potential role in continual maintenance of muscle activity. Aging (Albany NY). 13:24524-24541. https://doi.org/10.18632/aging.203720

14. Holtze S, Gorshkova E, Braude S, Cellerino A, Dammann P, Hildebrandt TB, Hoeflich A, Hoffmann S, Koch P, Terzibasi Tozzini E, Skulachev M, Skulachev VP, Sahm A. (2021). Alternative animal models of aging research. Frontiers in Molecular Biosciences, 8, 311. https://doi.org/10.3389/fmolb.2021.660959

15. Del Marmol D, Holtze S, Kichler N, Sahm A, Bihin B, Bourguignon V, Dogné S, Szafranski K, Hildebrandt TB, Flamion B. (2021). Abundance and size of hyaluronan in naked mole-rat tissues and plasma. Scientific Reports 11,7951. https://doi.org/10.1038/s41598-021-86967-9

16. Walz M, Höflich C, Walz C, Ohde D, Brenmoehl J, Sawitzky M, Vernunft A, Zettl UK, Holtze S, Hildebrandt TB, Wolf E, Hoeflich A. (2021). Development of a Sensitive Bioassay for the Analysis of IGF-Related Activation of AKT/mTOR Signaling in Biological Matrices. Cells 10, 482. https://doi.org/10.3390/cells10030482

17. Braude S*, Holtze S*, Begall S, Brenmoehl J, Burda H, Dammann P, del Marmol D, Gorshkova E, Henning Y, Hoeflich A, Höhn A, Jung T, Hamo D, Sahm A, Shebzukhov Y, Šumbera R, Miwa S, von Zglinicki T, Hildebrandt TB. (2021). Surprisingly long survival of pre-mature conclusions about naked mole-rat biology. Biological Reviews 96, 376-393. https://doi.org/10.1111/brv.12660

18. Holtze S, Koch R, Hildebrandt TB, Lemma A, Szafranski K, Platzer M, Alemayehu F, Goeritz F, Braude S. (2020). Hematologic adaptation to the subterranean environment by the naked mole-rat, Heterocephalus glaber (Ctenohystryca: Heterocephalidae). Journal of Mammalogy, 100, 1000-1009. https://doi.org/10.1093/jmammal/gyaa053

19. Braude S, Holtze S, Hildebrandt T, Koch R. (2020). Naked mole‐rats do not disperse or deliver pups in correlation with moon phase. African Journal of Ecology Afr J Ecol., 00:1–4. https://doi.org/10.1111/aje.12721

20. Eldarov CM, Vangely IM, Vays VB, Sheval EV, Holtze S, Hildebrandt TB, Kolosova NG, Popkov VA, Plotnikov EY, Zorov DB, Bakeeva LE, Skulachev VP. (2020). Mitochondria in the Nuclei of Rat Myocardial Cells. Cells 9, 712. https://doi.org/10.3390/cells9030712

21. Vyssokikh MY, Holtze S, Averina OA, Lyamzaev KG, Panteleeva AA, Marey MV, Zinovkin RA, Severin FF, Skulachev MV, Fasel N, Hildebrandt TB, Skulachev VP. (2020). Mild depolarization of the inner mitochondrial membrane is a crucial component of an anti-aging program. Proceedings of the National Academy of Sciences, 117(12), 6491-6501. https://doi.org/10.1073/pnas.1916414117

22. Carmeli-Ligati S, Shipov A, Dumont M, Holtze S, Hildebrandt T, Shahar R (2019). The structure, composition and mechanical properties of the skeleton of the naked mole-rat (Heterocephalus glaber). Bone. 128:115035. https://doi.org/10.1016/j.bone.2019.115035

23. Shebzukhov Y, Holtze S, Hirseland H, Schäfer H, Radbruch A, Hildebrandt T, Grützkau A. (2019). Identification of cross-reactive antibodies for the detection of lymphocytes, myeloid cells and haematopoietic precursors in the naked mole rat. Eur J Immunol 49, 2103-2110. https://doi.org/10.1002/eji.201948124

24. Dammann P, Scherag A, Zak N, Szafranski K, Holtze S, Begall S, Burda H, Kestler HA, Hildebrandt T, Platzer M (2019). Comment on 'Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age'. eLife. 2019;8. https://doi.org/10.7554/eLife.45415

25. Shekhidem AH, Sharvit L, Leman E, Manov I, Roichman A, Holtze S, M Huffman D, Y Cohen H, Hildebrandt T, Shams I, Atzmon G (2019). Telomeres and Longevity: A Cause or an Effect? International journal of molecular sciences 20, 3233. https://doi.org/10.3390/ijms20133233

26. Bakeeva L, Vays V, Vangeli I, Eldarov C, Holtze S, Hildebrandt T, Skulachev V (2019). Delayed Onset of Age-Dependent Changes in Ultrastructure of Myocardial Mitochondria as One of the Neotenic Features in Naked Mole Rats (Heterocephalus glaber). Int J Mol Sci 20, 566. https://doi.org/10.3390/ijms20030566

27. Bens M, Szafranski K, Holtze S, Sahm A, Groth M, Kestler HA, Hildebrandt TB, Platzer M (2018). Naked mole-rat transcriptome signatures of socially-suppressed sexual maturation and links of reproduction to aging. https://doi.org/10.1186/s12915-018-0546-z

28. Heinze I, Bens M, Calzia E, Holtze S, Dakhovnik O, Vyssokikh M, Sahm A, Kirkpatrick JM, Szafranski K, Romanov N, Singer S, Ermolaeva M, Platzer M, Hildebrandt TB, Ori A (2018). Species comparison of liver proteomes reveals links to naked mole-rat longevity and human aging. BMC Biol 16,82. https://doi.org/10.1186/s12915-018-0547-y

29. Sahm A, Bens M, Szafranski K, Holtze S, Groth M, Görlach M, Calkhoven C, Müller C, Schwab M, Kestler HA, Cellerino A, Burda H, Hildebrandt TB, Dammann P, Platzer M (2018). Long-lived rodents reveal signatures of positive selection in genes associated with lifespan. PLoS genetics 14.3: e1007272. https://doi.org/10.1371/journal.pgen.1007272

30. Holtze S, Braude S, Lemma A, Koch R, Morhart M, Szafranski K, Platzer M, Alemayehu F, Goeritz F, Hildebrandt TB (2017). The microenvironment of naked mole-rat burrows in East Africa. Afr J Ecol. 56, 279-289. https://doi.org/10.1111/aje.12448

31. Debebe T, Biagi E, Soverini M, Holtze S, Hildebrandt TB, Birkemeyer C, Wyohannis D, Lemma A, Brigidi P, Savkovic V, König B, Candela M, Birkenmeier G (2017): Unraveling the gut microbiome of the long-lived naked mole-rat. Sci Rep 7:9590. https://doi.org/10.1038/s41598-017-10287-0

32. Skulachev VP*, Holtze S*, Vyssokikh MY, Bakeeva LE, Skulachev MV, Markov AV, Hildebrandt TB*, Sadovnichii VA* (2017): Neoteny, Prolongation of Youth: From Naked Mole Rats to "Naked Apes" (Humans). Physiol Rev 97, 699-720. https://doi.org/10.1152/physrev.00040.2015

33. Holtze S, Eldarov CM, Vays VB, Vangeli IM, Vysokikh MY, Bakeeva LE, Skulachev VP, Hildebrandt TB (2016): Study of Age-Dependent Structural and Functional Changes of Mitochondria in Skeletal Muscles and Heart of Naked Mole Rats (Heterocephalus glaber). Biochemistry (Mosc) 81, 429-1437. https://doi.org/10.1134/S000629791612004X

34. Debebe T, Holtze S, Morhart M, Hildebrandt TB, Rodewald S, Huse K, Platzer M, Wyohannes D, Yirga S, Lemma A, Thieme R, König B, Birkenmeier G (2016): Analysis of cultivable microbiota and diet intake pattern of the long-lived naked mole-rat. Gut Pathog 28, 8-25. https://doi.org/10.1186/s13099-016-0107-3

35. Montero AG, Vole C, Burda H, Malkemper EP, Holtze S, Morhart M, Saragusty S, Hildebrandt TB, Begall S (2016): Non-Breeding Eusocial Mole-Rats Produce Viable Sperm—Spermiogram and Functional Testicular Morphology of Fukomys anselli. PloS one 11, e0150112. https://doi.org/10.1371/journal.pone.0150112

36. Dziegelewska M, Holtze S, Vole C, Wachter U, Menzel U, Morhart M, Groth M, Szafranski K, Sahm A, Sponholz C, Dammann P, Huse K, Hildebrandt T, Platzer M (2016): Low sulfide levels and a high degree of cystathionine β-synthase (CBS) activation by S-adenosylmethionine (SAM) in the long-lived naked mole-rat. Redox Biol 8, 192-198. https://doi.org/10.1016/j.redox.2016.01.008

37. Bens M, Sahm A, Groth M, Jahn N, Morhart M, Holtze S, Hildebrandt TB, Platzer M, Szafranski K (2016): FRAMA: from RNA-seq data to annotated mRNA assemblies. BMC Genomics 17, 54. https://doi.org/10.1186/s12864-015-2349-8

38. Thieme R, Kurz S, Kolb M, Debebe T, Holtze S, Morhart M, Huse K, Szafranski K, Platzer M, Hildebrandt TB, Birkenmeier G (2015): Analysis of Alpha-2 Macroglobulin from the Long-Lived and Cancer-Resistant Naked Mole-Rat and Human Plasma. PLoS One 10, e0130470. https://doi.org/10.1371/journal.pone.0130470

39. Roellig K, Drews B, Goeritz F, Hildebrandt TB (2011): The long gestation of the small naked mole-rat (Heterocephalus glaber Rüppell, 1842) studied with ultrasound biomicroscopy and 3D-ultrasonography. PloS one 6, e17744. https://doi.org/10.1371/journal.pone.0017744