Unusual ratio between free thyroxine and free triiodothyronine in a long-lived mole-rat species with bimodal ageing

PLoS One. 2014 Nov 19;9(11):e113698. doi: 10.1371/journal.pone.0113698. eCollection 2014.


Ansell's mole-rats (Fukomys anselli) are subterranean, long-lived rodents, which live in eusocial families, where the maximum lifespan of breeders is twice as long as that of non-breeders. Their metabolic rate is significantly lower than expected based on allometry, and their retinae show a high density of S-cone opsins. Both features may indicate naturally low thyroid hormone levels. In the present study, we sequenced several major components of the thyroid hormone pathways and analyzed free and total thyroxine and triiodothyronine in serum samples of breeding and non-breeding F. anselli to examine whether a) their thyroid hormone system shows any peculiarities on the genetic level, b) these animals have lower hormone levels compared to euthyroid rodents (rats and guinea pigs), and c) reproductive status, lifespan and free hormone levels are correlated. Genetic analyses confirmed that Ansell's mole-rats have a conserved thyroid hormone system as known from other mammalian species. Interspecific comparisons revealed that free thyroxine levels of F. anselli were about ten times lower than of guinea pigs and rats, whereas the free triiodothyronine levels, the main biologically active form, did not differ significantly amongst species. The resulting fT4:fT3 ratio is unusual for a mammal and potentially represents a case of natural hypothyroxinemia. Comparisons with total thyroxine levels suggest that mole-rats seem to possess two distinct mechanisms that work hand in hand to downregulate fT4 levels reliably. We could not find any correlation between free hormone levels and reproductive status, gender or weight. Free thyroxine may slightly increase with age, based on sub-significant evidence. Hence, thyroid hormones do not seem to explain the different ageing rates of breeders and non-breeders. Further research is required to investigate the regulatory mechanisms responsible for the unusual proportion of free thyroxine and free triiodothyronine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Amino Acid Sequence
  • Animals
  • Female
  • Guinea Pigs
  • Immunoenzyme Techniques
  • Male
  • Mole Rats
  • Molecular Sequence Data
  • Rats
  • Rats, Wistar
  • Sequence Alignment
  • Thyroid Hormone Receptors alpha / chemistry
  • Thyroid Hormone Receptors alpha / metabolism
  • Thyroid Hormone Receptors beta / chemistry
  • Thyroid Hormone Receptors beta / metabolism
  • Thyroxine / blood*
  • Triiodothyronine / blood*


  • Thyroid Hormone Receptors alpha
  • Thyroid Hormone Receptors beta
  • Triiodothyronine
  • Thyroxine

Associated data

  • GENBANK/KJ958510
  • GENBANK/KJ958511
  • GENBANK/KJ958512
  • GENBANK/KJ958513
  • GENBANK/KJ958514
  • GENBANK/KJ958515
  • GENBANK/KJ958516
  • GENBANK/KJ958517
  • GENBANK/KJ958518
  • GENBANK/KJ958519
  • GENBANK/KJ958520
  • GENBANK/KM676335

Grants and funding

This work was supported by a grant of the German Research Foundation to PD (DFG-grant DA 992/3-1) (http://www.dfg.de/). The publication fee was funded by the “Publish Open Access”-Program of the University of Duisburg-Essen and the German Research Foundation.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.