Molecular basis of delayed ageing in mammals with highly divergent ageing rates: African mole-rats Fukomys sp. (Rodentia)

• Antragsteller: Dr. Philip Dammann; Privatdozent Dr. Matthias Platzer
• Fachliche Zuordnung: Biochemie und Physiologie der Tiere ; Evolution, Anthropologie ; Gerontobiologie und Geriatrie
• Förderung: Förderung von 2013 bis 2017
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 236365560

The increase in life expectancy and age-related diseases represents an ethical and economic challenge to human society. Therefore a better understanding of the molecular basis of the ageing process, especially in long-lived organisms like ourselves, remains an important goal. Our project aims to identify molecular networks underlying delayed ageing in a very promising new model for ageing research, namely the African mole-rat genus Fukomys. These subterraneous, long-lived rodents (max. lifespan approx. 20 years) live in enlarged family groups where only few individuals breed while all others forego own reproduction. On average, Fukomys breeders live approximately twice as long as non-breeders. Such a pronounced benefit of reproduction for longevity is unparalleled in any other vertebrate group studied thus and greater than most experimental interventions that extended lifespan in vertebrates, such as caloric restriction or application of resveratrol or rapamycin. Moreover, this phenotype contrasts the trade-off between fecundity and lifespan observed in many species across all animal taxa and therewith challenges established theories of ageing. Fukomys sp. thus provide a unique, hitherto unavailable opportunity to study the mechanisms of "fast" vs. "slow" mammalian ageing by following highly divergent ageing rates within the same genetic configuration, without the need to control for potentially confounding variables such as phylogeny, ontogeny, morphology, nutrition, or environment. Following a tightly controlled experimental set-up with multiple measurements on the same test individuals before and after onset of sexual activity, we will study changes in transcriptome profiles in parallel with other ageing-related traits (telomere length, oxidative stress and proteomic stability). The general objective is to gain new insights into the maintenance of molecular homeostasis that reduce the accumulation of cellular and physiological damage which eventually leads to age-related diseases and death. This will allow examination of the applicability of several of the most influential and, sometimes, controversially discussed theories of ageing to the exceptional phenotype observed for Fukomys sp. and thus will also make a contribution to the knowledge basis essential for translation into sustained health in an ageing human society. In addition, comparative transcriptome data analysis will contribute to a deeper understanding of the link between eusociality and extreme longevity, and will also help to answer the longstanding question whether eusociality originated once in a common ancestor or multiple times independently in the family of mole-rats (Bathyergidae).

• DFG-Verfahren: Sachbeihilfen