- Molecular Mechanisms of Aging and Age-Related Diseases
- mitochondria, mitochondrial protein import, age-related diseases, Alzheimer's disease, Parkinson's disease, proteomics, structural biology, fluorescence spectroscopy
We study adaptive stress responses and their many instigators as interventions for healthy longevity.
We employ invertebrate models, predominantly C. elegans, to investigate basic mechanisms of ageing and age-dependent diseases and develop interventions targeting them. I am particularly interested in exploiting emerging automation and omics- technologies together with computational tools to develop ageing biomarkers and novel pharmacological interventions against ageing.
- mitochondrial sirtuins
- cell cycle
Our research is focused on the biochemical and molecular basis of longevity‚ in particular the role played by mitochondria in healthspan regulation and prevention of metabolic diseases. Contrary to the widely re-iterated Free Radical Theory of Aging, Ristow was the first to show that the health-promoting effects associated with low caloric intake, physical exercise and other lifespan-extending interventions like sirtuin signaling are caused by increased formation of Reactive Oxygen Species (ROS) within the mitochondria, causing a vaccination-like adaptive response that culminates in increased stress resistance and extended longevity, a process called mitohormesis. He works with the roundworm C. elegans and mammalian model organisms, as well as humans. Based on these findings, Ristow has subsequently identified FDA-approved compounds and novel phytochemicals as candidates for the promotion of human healthspan, while corresponding randomized double-blinded clinical trials are pending.
The primary focus of our research is in deciphering the precise signaling cascade of the pathogenic mechanisms leading to mitochondrial diseases and ageing, with the ultimate goal of identifying new therapeutic targets and strategies.
My lab primarily exploits the nematode C. elegans as a powerful genetic model organism to unravel the role of mitochondrial stress responses in neurodegenerative processes, from developmet to aging. To this end, we recently developed a high-content phenotype-based screening pipeline to identify compounds (e.g. food components and conatminants) acting through mitochondria-stress responses to impact neuronal diseases and aging.