Telomere shortage as model for microglia aging and its implication for neuronal survival

• Applicant: Dr. Knut Biber
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 233599527

Microglia, important neuroprotective cells in the brain, are affected by aging in a species dependent manner. Aged human and mouse microglia aquire different morphologies and most likely have different properties. In humans show aged microglia a dystrophic morphology and most likely impaired neuroprotective protective function. In aged mice, appear microglia in a hypertrophic morphology and potentially harm neurons activally. These differences are striking and hamper the translatability of mouse results to humans. It is known that cellular aging differs between laboratory mice and humans. For example, the effects of telomere shortening is important for cellular aging in humans but not in mice. Since laboratory mice have much longer telomeres cellular aging due to telomere shortage does not occur here. Only in mice without telomere elongation (TERC-/- animals) this form of cellular aging is observable. We show here for the first time that microglia in aged TERC-/- animals resemble the dystrophic morphology of aged human microglia. Using aged TERC-/- animals we propose to analyze in vitro and in vivo the properties and function of dystrophic microglia in comparison to aged microglia from control animals This proposal will thus not only elucidate the function of dystrophic microglia for neuron survival, but will also increase the translatability of mouse research to the human situation.

• DFG Programme: Research Grants