Within the framework of projects granted by the Leibniz Association (Senatsausschuss Wettbewerb, SAW) and the German Research Foundation (Deutschen Forschungsgemeinschaft, DFG), FLI-researchers wanted to identify molecular networks responsible for a long life in health by means of the naked mole-rat (Heterocephalus glaber) and several mole-rat species of the Fukomys clade. The innovative omics research approaches are collaborations with the Leibniz Institute for Zoo and Wildlife Research (IZW) in Berlin, the University of Duisburg-Essen and others.
The Naked Mole-Rat
Mouse-sized naked mole-rats, who live in the East African savanna, are very exciting for age research: they can live as long as 30 years, and they do not suffer from age-related diseases – in contrast to humans and to other rodents. So far, among hundreds of examined animals of this species, only a handful cases of cancer were observed. The rodents are perfectly adapted to a life below ground (zoological family: blesmols, Bathyergidae), they build extensive tunnel systems, which they almost never leave. Under these conditions, they have developed a unique division of labor: like state-building insects (honeybees, ants, termites), only one female mole-rat reproduces; brood care, food-procurement as well as the enlargement and defense of their burrow system are practiced collaboratively.
Astonishingly, the breeding “queen” lives much longer than her conspecifics. It is in total contradiction to the common theory of aging in which organisms invest their energy either in reproduction or in conservation of its body functions. The scientists have several samples from a mole-rat-breeding program as well as samples from free-living mole-rats from international cooperation partners, to explain how mole-rat queens combine extreme physical exertion of consecutive pregnancies with remarkable health and longevity.
The mouse-sized Ansell's mole-rat and rat-sized giant mole-rat can live longer than 20 years. Since only few animals could be observed under laboratory conditions so far, it might even be possible that they can life as long as the naked mole-rat. Also in other respects, the two species of the Fukomys genus have much in common with the naked mole-rat: they dig under ground tunnel systems, can be found only in Africa - in the areas southern of the Sahara - and they live in state-like structures with division of labor. Both, the pasha and the queen of a Fukomys mole-rat colony, can reach twice the lifespan of their workers - a difference, which is even larger than in the naked mole-rat. Scientists analyze samples from animals of different castes (pasha/queen as well as workers) and of different ages in order to explain the remarkable lifespan differences between castes and, moreover, the longevity of the mole-rats in comparison to much shorter-lived, closely related rodents.
With the help of modern genomic, transcriptomic and proteomic technologies, the researchers measure how intense the different genes are expressed. They compare sequences of mole-rats and their expression patterns to those of short- and long-lived species to identify evolutionary adaptations in genes and metabolic pathways that may be responsible for unusual long and healthy life of mole-rats.
Collaboration Partners (Selection)
Leibniz Institute for Zoo and Wildlife Research (Thomas B. Hildebrandt)
Washington University in St. Louis (Stan Braude)
- University of Duisburg-Essen (Philip Damman, Hynek Burda)
Begall S, Nappe R, Hohrenk L, Schmidt TC, Burda H, Sahm A, Szafranski K, Dammann P, Henning Y. Life expectancy, family constellation and stress in giant mole-rats (Fukomys mechowii). Philos Trans R Soc Lond B Biol Sci 2021, 376(1823), 20200207. [PubMed]
Sahm A, Platzer M, Koch P, Henning Y, Bens M, Groth M, Burda H, Begall S, Ting S, Goetz M, Van Daele P, Staniszewska M, Klose JM, Costa PF, Hoffmann S, Szafranski K, Dammann P. Increased longevity due to sexual activity in mole-rats is associated with transcriptional changes in the HPA stress axis. eLife. 2021, 10, e57843. [eLife]
Dammann P, Scherag A, Zak N, Szafranski K, Holtze S, Begall S, Burda H, Kestler HA, Hildebrandt T, Platzer M. Comment on 'Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age'. eLife 2019, 8, e45415. [eLife]
Bens M, Szafranski K, Holtze S, Sahm A, Groth M, Kestler HA, Hildebrandt TB, Platzer M. Naked mole-rat transcriptome signatures of socially suppressed sexual maturation and links of reproduction to aging. BMC Biol 2018, 16(1), 77. [PubMed]
Heinze I, Bens M, Calzia E, Holtze S, Dakhovnik O, Sahm A, Kirkpatrick JM, Szafranski K, Romanov N, Sama SN, Holzer K, Singer S, Ermolaeva M, Platzer M, Hildebrandt T, Ori A. Species comparison of liver proteomes reveals links to naked mole-rat longevity and human aging. BMC Biol. 2018, 16(1), 82. [PubMed]
Henning Y, Mladěnková N, Burda H, Szafranski* K, Begall* S. Retinal S-opsin dominance in Ansell's mole-rats (Fukomys anselli) is a consequence of naturally low serum thyroxine. Sci Rep 2018, 8(1), 4337. *equal contribution [PubMed]
Holtze S, Braude S, Lemma A, Koch R, Morhart M, Szafranski K, Platzer M, Alemayehu F, Goeritz F, Hildebrandt TB. The microenvironment of naked mole-rat burrows in East Africa. Afr J Ecol 2018, 56(2), 279-289. [DOI]
Olecka M, Huse K, Platzer M. The high degree of cystathionine β-synthase (CBS) activation by S-adenosylmethionine (SAM) may explain naked mole-rat's distinct methionine metabolite profile compared to mouse. Geroscience 2018, 40(4), 359-360. [PubMed]
Sahm A, Bens M, Szafranski K, Holtze S, Groth M, Görlach M, Calkhoven C, Müller C, Schwab M, Kraus J, Kestler HA, Cellerino A, Burda H, Hildebrandt T, Dammann P, Platzer M. Long-lived rodents reveal signatures of positive selection in genes associated with lifespan. PLoS Genet 2018, 14(3), e1007272. [PubMed]
Sahm A, Bens M, Platzer M, Szafranski K. PosiGene: automated and easy-to-use pipeline for genome-wide detection of positively selected gene. Nucleic Acids Res 2017, 45(11), e100. [PubMed]
Bens M, Sahm A, Groth M, Jahn N, Morhart M, Holtze S, Hildebrandt TB, Platzer M, Szafranski K. FRAMA: from RNA-seq data to annotated mRNA assemblies. BMC Genomics 2016, 17, 54. [PubMed]
Debebe T, Holtze S, Morhart M, Hildebrandt TB, Rodewald S, Huse K, Platzer M, Wyohannes D, Yirga S, Lemma A, Thieme R, Konig B, Birkenmeier G. Analysis of cultivable microbiota and diet intake pattern of the long-lived naked mole-rat. Gut Pathog 2016, 8, 25 [PubMed]
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. Low sulfide levels and a high degree of cystathionine beta-synthase (CBS) activation by S-adenosylmethionine (SAM) in the long-lived naked mole-rat. Redox Biol 2016, 8, 192-198. [PubMed]
Thieme R, Kurz S, Kolb M, Debebe T, Holtze S, Morhart M, Huse K, Szafranski K, Platzer M, Hildebrandt TB, Birkenmeier G. Analysis of Alpha-2 Macroglobulin from the Long-Lived and Cancer-Resistant Naked Mole-Rat and Human Plasma. PLoS One 2015, 10(6), e0130470. [PubMed]
Henning Y, Vole C, Begall S, Bens M, Broecker-Preuss M, Sahm A, Szafranski K, Burda H, Dammann P. Unusual ratio between free thyroxine and free triiodothyronine in a long-lived mole-rat species with bimodal ageing. PLoS One 2014, 9(11), e113698. [PubMed]
Roellig K, Drews B, Goeritz F, Hildebrandt TB. The long gestation of the small naked mole-rat (Heterocephalus glaber Rüppell, 1842) studied with ultrasound biomicroscopy and 3D-ultrasonography. PLoS One 2011, 6(3), e17744. [PubMed]
Yu C, Li Y, Holmes A, Szafranski K, Faulkes CG, Coen CW, Buffenstein R, Platzer M, de Magalhães JP, Church GM. RNA sequencing reveals differential expression of mitochondrial and oxidation reduction genes in the long-lived naked mole-rat when compared to mice. PLoS One 2011, 6(11), e26729. [PubMed]