Aging is the greatest risk factor for most chronic diseases. Yet the
mechanisms that determine how organisms age remain largely unknown.
The Brunet Lab investigates how genetic, epigenetic, and metabolic factors regulate aging across
scales. By integrating discoveries from
C. elegans, the African killifish, mice,
and human cells, we uncover fundamental principles that
promote healthy longevity.
We combine multi-omic approaches, AI, stem cell biology, neuroscience, and evolutionary biology to uncover the fundamental mechanisms that regulate aging. We leverage complementary organisms and systems that allow us to discover conserved principles of longevity across the tree of life.
Conserved longevity pathways
Organismal aging and 'suspended animation'
Stem cells and brain aging
Translation to human biology
Our laboratory addresses several interconnected questions that probe how organisms age and how healthy lifespan may be extended.
Diet profoundly influences lifespan. But the mechanisms that connect nutrient availability to healthy aging remain incompletely understood. Our laboratory explores how nutrient-sensing pathways, lipid metabolism, and metabolites regulate longevity across species. We want to understand how metabolic adaptations promote long-term organismal survival and longevity.
Ruetz et al, Nature (2024)
Papsdorf et al. Nature Cell Biology (2023)
Han et al. Nature (2017)
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Environmental factors – including exercise, stress, and sexual interaction – exert surprisingly persistent effects on aging. Our research explores how chromatin and epigenetic mechanisms encode these long-lasting responses. Our laboratory showed that chromatin modifiers can regulate lifespan and contribute to transgenerational inheritance of longevity in C. elegans. We determine how molecular and cellular networks change with age, and how this influences regenerative capacity and healthy aging.
Yeo et al. Nature Aging (2023)
Hu et al. Science (2020)
Greer et al. Nature (2011)
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Adult stem cells maintain tissue homeostasis. Yet their regenerative potential declines during aging. Our laboratory studies the molecular pathways that preserve stem cell function and investigates strategies to rejuvenate old stem cells. A major focus is the biology of neural stem cells, combining transcriptomics, epigenomics, metabolomics, and functional studies to understand how regenerative capacity changes with age.
Buckley et al. Nature Aging (2023)
Dulken et al. Nature (2019)
Leeman et al. Science (2018)
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The aging brain undergoes profound molecular and cellular changes that contribute to cognitive decline and neurodegenerative disease. Our laboratory investigates the mechanisms that preserve brain function throughout life and explores strategies to rejuvenate aging neural tissues. By integrating molecular genetics and neuroscience, we seek to identify pathways that maintain neural plasticity and promote healthy brain aging.
Bedbrook et al. Science (2026)
Navarro et al. Immunity (2026)
Sun et al. Nature (2025)
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The African killifish is the shortest-lived vertebrate that can be maintained in the laboratory, providing a unique opportunity to investigate the genetics and evolution of aging. Our laboratory pioneered this emerging model system and developed many of the genetic and genomic tools now used by the research community. The killifish allows us to study vertebrate aging and the remarkable suspended-animation state known as diapause.
Singh et al. Cell (2024)
Harel et al. Cell (2015)
Valenzano et al. Cell (2015)
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We want to answer fundamental questions about the biology of aging:
How do diet, exercise, sexual interaction, and stress produce lasting effects on longevity?
Can regenerative tissues and stem cells restore youthful organ function?
What evolutionary mechanisms determine lifespan across species?
Can diapause reveal new principles for preserving tissues and organs?