Metabolic flexibility
for healthy aging.
We study how cells and organisms switch fuels as nutrients come and go, why that capacity fades with age, and how restoring it can add healthy years to life.
Why does growing old make us sick? Age is the biggest risk factor for almost every chronic disease. We want to know why, and whether it has to be that way.
Most chronic diseases, including neurodegenerative disorders, cardiovascular disease, stroke, cancer, metabolic disease and osteoporosis, become more common with age. Yet eating less or fasting slows aging and delays these diseases in nearly every organism studied, while obesity speeds them up.
The common thread is metabolism. A young body switches easily between fuels, from fed to fasted, and recovers quickly. We call this capacity metabolic flexibility, and we think its loss drives aging. Our goal is to find the mechanisms behind it and restore it, capturing the benefits of dietary restriction without its costs.
Homeodynamics, not homeostasis
Aging is usually described as a loss of homeostasis, a drift away from a fixed set point. We see it as a loss of dynamic range. Young systems respond widely and recover quickly as conditions change. Old systems respond less, and more slowly.
So the goal isn’t to lock biology into one “youthful” state. It is to restore the capacity to respond.
Keeping metabolism flexible as we age
We study how cells and organisms sense nutrients and switch metabolic state, why that flexibility is lost with age, and how to restore it. We use whatever system best answers the question, from cells and mice to people and short-lived model organisms.
Nutrient and energy sensing
How AMPK and mTORC1 read a cell’s fuel state and coordinate flexible responses across the body.
Read more → 02Organelle remodeling
How mitochondria and peroxisomes physically reshape to switch between fuels, and why that stalls with age.
Read more → 03RNA splicing and lipids
How splicing and the epigenome tune lipid metabolism, and set how well longevity interventions work.
Read more → 04Precision geroscience
Biomarkers that predict who benefits from which intervention, from cells to people.
Read more →Recent & landmark work
From the lab
Help us add healthy years to life
Philanthropy lets us pursue bold, early-stage ideas that are rarely funded by traditional grants, and keeps discovery moving when federal support is uncertain. Gifts of any size can support the lab’s research, our trainees, or the Harvard Chan Healthy Aging Initiative.
If you’re interested in supporting our work, I’d be glad to talk. Please get in touch directly.
William Mair, Professor of Molecular Metabolism
Curious about why we age? Come find out.
We welcome postdocs, graduate students and research staff who want to do rigorous, creative science on the biology of aging in a lab that looks after its people.
Opportunities →