Max Planck Institute for Biology of Ageing

Endogenous metabolite directly inhibits mTORC1 activity

How a single enzyme unleashes a complex DNA repair process

Study on mice shows male-specific effects on health

Coenzyme Q distribution within the cell is regulated by mitochondria

Studies in fruit flies reveal how the sex determines the responses to the anti-ageing drug rapamycin

Linda Partridge and her colleague Sebastian Grönke at the Max Planck Institute for Biology of Ageing in Cologne can’t promise eternal life – but they are at least discovering ways to lead a healthier one. The researchers’ findings in fruit flies and mice have revealed astonishing new insights into ageing that will also benefit us humans.

Life is short, especially for the turquoise killifish, Nothobranchius furzeri: it lives for only a few months and then its time is up. During that short life span it passes through every phase of life, from larva to venerable old fish. Its brief life expectancy – unusual for a vertebrate – has long fascinated Dario Valenzano of the Max Planck Institute for Biology of Ageing in Cologne. In just ten years, he has turned it into a model organism for research on aging.

Imagine you could take a medicine that combats the ill health that comes with age, and keeps you living healthily for longer. Scientists are trying to find a drug that has these effects. The current most promising anti-ageing drug is Rapamycin, known for its positive effects on health and lifespan in laboratory animals. However, potential negative side effects and a lack of clinical data for its effects hold back its usage as a geroprotector. Our findings are helping to understand how this drug works, to open new doors for a potential application in humans.

As we are ageing, our bones become thinner, we suffer fractures more often, and bone-diseases such as osteoporosis are more likely to occur. One responsible mechanism involves the impaired function of the bonemarrow-resident mesenchymal stem cells, which are required for the maintenance of bone integrity. We now have been able to show that these changes can be reversed by rejuvenating the epigenome. Such approach could contribute to the treatment of diseases such as osteoporosis in the future.

Mitochondria, essentially domesticated microbes in our cells, play a defensive role during microbial infection. In previous work, we showed that mitochondria can compete with the human parasite Toxoplasma gondii for fatty acids, thereby restricting its growth. Here, we further investigated the metabolic conflict between mitochondria and Toxoplasma. We report a novel structure we term SPOT - structure positive for outer mitochondrial membrane - that emerges from the outer mitochondrial membrane due to mitochondrial import stress caused by the Toxoplasma.

Many cancers reprogram cellular metabolism in order to sustain tumour growth. Mitochondria are essential organelles which provide cancer cells with the metabolic flexibility required in challenging environmental conditions. Our recent work has revealed that tumour cells growing in low oxygen or nutrient deprived conditions are able to rewire their mitochondria by degrading specific mitochondrial proteins. We propose that analyzing this mechanism will provide therapeutic targets in hard-to-treat tumours such as pancreatic cancer.

ADP-ribosylation (ADPr) is a protein modifier playing key roles in health and disease, from bacterial pathogenesis to cancer. Yet for decades it has been difficult to investigate the detailed mechanism of this modification. Using advanced proteomics, we discovered serine ADPr (Ser-ADPr) as a new and widespread protein marker needed for DNA damage response and were able to describe its biochemical basis by identifying its “writers” and “eraser”. These discoveries opened a large and novel research area into how ADPr regulates essential cellular processes.