Andrew Pickering, Ph.D.

Areas of Interest

Research Interests

The Pickering lab is interested in biological questions about the aging process with the goal of development of treatments to allow people to stay healthy and active for longer. Our lab utilizes a number of model systems to answer these questions including fruit flies, mice and cell lines from long and short-lived animal species. Our particular focus is the role of proteostasis in aging and neurodegenerative diseases. We have demonstrated a modulatory role for the proteasome system in brain aging and Alzheimer’s disease. We have also shown tradeoff between protein synthesis and aging. 

The proteasome in aging and Alzheimer’s disease 

We are interested in the role of the proteasome system in aging and age-related diseases. We have found the proteasome system to be elevated in species that are under selection to be longer lived, a process that appears primarily driven by increases in the Immunoproteasome. In addition, we have reported neuronal-specific but not-ubiquitous proteasome augmentation to extend lifespan and slow age-related cognitive declines. Further, we have demonstrated proteasome augmentation to delay AD-like pathologies and developed a set of novel proteasome agonists. 

Early life protein translation in aging and lifespan 

We are interested in modulation of protein translation in lifespan. We have found protein translation to be elevated in early-life with a decline in protein translation rates across lifespan. We discovered that this represented an active repression of protein translation rates in later life to prevent or reduce later life proteostasis collapse. We demonstrated repression of protein translation in early life to significantly extend organismal lifespan though at the cost of early life reproduction. This is produced through a process involving juvenile hormone, modulation of accumulation of large lipid transfer proteins, regulation of germline stem cell proliferation and stress response pathways. 

The mitochondrial thioredoxin system a metabolic and aging regulator 

We are interested in the thioredoxin pathway. We became interested in this pathway after finding it to be enriched in species which are under selection to be long-lived. We specifically found elevations in the mitochondrial thioredoxin system in long lived species of rodent primates and birds. We went on to show that This system was elevated in several slow aging mouse models and that augmentation of the enzyme in the fruit fly Drosophila melanogaster could extend lifespan and improve activity at older ages. Furthermore, we have reported a role for the mitochondrial thioredoxin system as a novel metabolic regulator and to protect against metabolic disease.