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Aging in LIving Systems
Aging is the most universal phenomenon in nature, experienced by every living system on Earth.
For most organisms, aging is the central driver of death and disease.
However, there is extreme variation in the rate at which living systems decline, suggesting aging is malleable.
Our lab seeks to discover mechanisms of aging that can be targeted to delay or prevent disease.
Our Research
The Levine lab bridges bioinformatics and experimental approaches.
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Bioinformatics (Dry Lab): The bioinformatics team develops and applies advantaged computational methods to generate quantitative estimates of biological aging, or identify key molecular factors that may regulate aging. Building on this, we also seek to map multi-dimensional trajectories of cells, tissues, and organs as they move through time.
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Experimental (Wet Lab): The molecular biology team uses in vitro and in vivo experiments to identify drivers of cellular aging and test efficacy of interventions aimed at modifying or reversing age-related changes.
Epigenetic
Clocks
Epigenetic signatures convey instructions for every cell in your body, dictating everything from cellular identity/state to signaling. However, aging dramatically reshapes the epigenome, making these instructions less intelligible and ultimately contributing to cellular dysfunction. We are working on ways to model these changes and use that information to develop epigenetic measures of biological age. In the future, these measures can be used as outcomes of aging in clinical trials, glean insights into potential mechanisms of aging, and provide information on individual disease susceptibility.
Select Publications:
Epigenetic
Reprogramming
What determines a cell's identity? Differentiates an embryonic stem cell from an adult skin cell? The answer is our epigenome. The epigenome is the master conductor within each cell, directing information coded within the DNA to control the rate at which new cells are made, determine the physical structure/shape, dictate cellular responses to stress, and help maintain stability of cell populations. Unfortunately, this amazing biological operating system also acquires glitches with age. But what if, like the team members at the genius bar of your local Apple store can repair a faulty MacBook, scientists could reprogram the declining epigenetic system?
Cellular Aging Trajectories
In 1940, Conrad Waddington described a metaphorical epigenetic landscape through which cells traverse during differentiation. In Waddington’s landscape, a cell’s journey down the theoretical hillside culminates after differentiation. However, we hypothesize that the landscape actually continues as the epigenetic profiles and phenotypes of differentiated cells are dynamically modulated with aging. As with Newtonian physics, in which objects descend a hill in the absence of an opposing force, so too will cells move from states of pluripotency to differentiation, and then eventually to aging-induced failure. Our lab is utilizing single-cell transcriptomics and epigenomics to map the trajectories cells take during development, aging, reprogramming, and tumoregensis.
Alzheimer's
disease
Alzheimer’s disease (AD) is the fifth leading cause of death for those ages 65 and older. It is marked by a progressive decline in cognitive functioning and memory, culminating in the loss of independence and need for intensive and costly full-time care. As a result, the estimated 5.4 million Americans currently living with AD carry a huge societal and economic burden that with the lack of existing treatments will only grow over the coming decades. Our lab is interested in discovering the underlying molecular aging changes that drive etiology of AD. We are particularly focused on identifying epigenetic, proteomic, and lipidomic changes in various brain cells with aging. We are also investigating the role of cellular senescence and its interactions with hallmarks of AD, including the presence of insoluble amyloid oligomers. Finally, we are invested in discovering molecular pathways to resilience among genetically predisposed individuals..
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