Molekulare Grundlagen des verzögerten Alterns bei Säugetieren mit stark divergierenden Alternsraten: Afrikanischen Graumullen Fukomys sp. (Rodentia)

• Applicants: Dr. Philip Dammann; Privatdozent Dr. Matthias Platzer
• Subject Area: Animal Physiology and Biochemistry ; Evolution, Anthropology ; Biogerontology and Geriatric Medicine
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 236365560

• Final Report Year: 2018

Final Report Abstract

In summary, our results show that the large lifespan differences between breeders and non-breeders in Fukomys sp. are not caused by globally altered gene expression but presumably by more subtle changes that specifically affect mainly endocrine tissues and selected pathways. Many of the results underline the importance of target genes and concepts that are already heavily examined in aging research including our previous works, e.g. the mTOR-pathway or proteolytic systems. On the other hand, they also reveal interesting contradictions to the current knowledge, e.g. that strong up-regulation of protein synthesis and IGF1 in breeders are compatible with considerable lifespan extensions. We are optimistic that our results will contribute to new, more system-oriented perspectives on prolonging life- and healthspans. In that sense, the concrete genes, expression patterns and contradictions that were identified in this study with regard to lifespan regulation may become be promising targets for follow-up studies.

Publications

• Higher transcriptome stability during aging in long-lived giant mole-rats than in short-lived rats
  Sahm A, Bens M, Henning Y, Vole C, Groth M, Schwab M, Platzer M, Szafranski K, Dammann P
  (See online at https://doi.org/10.1101/251777)
• Unusual ratio between free thyroxine and free triiodothyronine in a long-lived mole-rat species with bimodal ageing. PLoS One 9: e113698 (2014)
  Henning Y, Vole C, Begall S, Bens M, Broecker-Preuss M, Sahm A, Szafranski K, Burda H, Dammann P
  (See online at https://doi.org/10.1371/journal.pone.0113698)
• FRAMA: from RNA-seq data to annotated mRNA assemblies. BMC Genomics 17: 54 (2016)
  Bens M, Sahm A, Groth M, Jahn N, Morhart M, Holtze S, Hildebrandt TB, Platzer M, Szafranski K
  (See online at https://doi.org/10.1186/s12864-015-2349-8)
• 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 8: 192-8 (2016)
  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
  (See online at https://doi.org/10.1016/j.redox.2016.01.008)
• Outgroups and Positive Selection: The Nothobranchius furzeri Case. Trends Genet 32: 523-5 (2016)
  Sahm A, Platzer M, Cellerino A
  (See online at https://doi.org/10.1016/j.tig.2016.06.002)
• Parallel evolution of genes controlling mitonuclear balance in short-lived annual fishes. Aging Cell 16: 488-496 (2017)
  Sahm A, Bens M, Platzer M, Cellerino A
  (See online at https://doi.org/10.1111/acel.12577)
• PosiGene: automated and easy-to-use pipeline for genome-wide detection of positively selected genes. Nucleic Acids Res 45: e100 (2017)
  Sahm A, Bens M, Platzer M, Szafranski K
  (See online at https://doi.org/10.1093/nar/gkx179)
• Slow aging in mammals—Lessons from African mole-rats and bats. Semin Cell Dev Biol, 70:154-163 (2017)
  Dammann P
  (See online at https://doi.org/10.1016/j.semcdb.2017.07.006)
• Long-lived rodents reveal signatures of positive selection in genes associated with lifespan. PLoS Genet 14: e1007272 (2018)
  Sahm A, Bens M, Szafranski K, Holtze S, Groth M, Gorlach M, Calkhoven C, Muller C, Schwab M, Kraus J, Kestler HA, Cellerino A, Burda H, Hildebrandt T, Dammann P, Platzer M
  (See online at https://doi.org/10.1371/journal.pgen.1007272)
• Naked mole-rat transcriptome signatures of socially-suppressed sexual maturation and links of reproduction to aging. BMC Biology
  Bens M, Szafranski K, Holtze S, Sahm A, Groth M, Kestler HA, Hildebrandt TB, Platzer M
  (See online at https://doi.org/10.1101/221333)
• Retinal S-opsin dominance in Ansell's mole-rats (Fukomys anselli) is a consequence of naturally low serum thyroxine. Sci Rep 8: 4337 (2018)
  Henning Y, Mladěnková N, Burda H, Szafranski K, Begall S
  (See online at https://doi.org/10.1038/s41598-018-22705-y)
• Species comparison of liver proteomes reveals links to naked mole-rat longevity and human aging. BMC Biology
  Heinze I, Bens M, Calzia E, Holtze S, Dakhovnik O, Sahm A, Kirkpatrick J, Szafranski K, Romanov N, Holzer K, Singer S, Ermolaeva M, Platzer M, Thomas Hildebrandt, Ori A
  (See online at https://doi.org/10.1101/220343)