RESEARCH
EPIGENETIC MANIPULATION OF AGING
Cellular machinery and information gradually deteriorate as entropy increases over time. The epigenome, operating as biological software, retains memories of cell states and provides resilience against stress. We have discovered that glitches in the epigenetic information cause aging in mammals, but restoring it through gene therapies or drugs can turn back the cellular clock and rejuvenate tissues. This suggests the pace and direction of aging can be epigenetically controlled. Our quest is to understand the molecular mechanisms of aging, both forward and in reverse, and to develop innovative strategies to reinstate the body’s youthfulness, with a primary focus on the brain.
EPIGENETIC DECODING OF BRAIN AGING
Investigating the epigenetic foundations of brain aging to restore a youthful mind.
​One of humanity's greatest fears is losing self-identity and becoming disconnected from reality—conditions that are triggered and profoundly worsened by brain aging. With the dramatic extension of the human lifespan over the last century, age-related brain diseases, including Alzheimer's, have become some of the fastest-growing health concerns and a significant social burden. Our goal is to determine whether and how the disruption of epigenetic information drives brain aging and exacerbates neurodegenerative diseases. By targeting the root cause rather than the specific symptoms of each disease, we aim to offer a unique opportunity to treat a wide range of brain pathologies.
NEXT GENERATION EPIGENTIC REJUVENATION
Developing new therapies that restore or stabilize youthful epigenome.
Every cell in our body operates using the same genetic information, yet distinct epigenetic information grants each cell type its unique identity and function. Our work suggests that the loss of youthful epigenetic information drives mammalian aging, highlighting that aging is more amenable than previously believed, due to the reversible nature of the epigenome. Our goal is to develop safe, cost-effective methods to reprogram the epigenome to its youthful state and identify new epigenetic targets for rejuvenation, thereby revitalizing aged tissues.
EROSION OF CELL IDENTITY
Investigating cellular identity noise as a cause of aging.
We have discovered that the developmental program and cell identity become increasingly noisy over time due to the smoothening of the epigenetic landscape, leading to a loss of tissue function. Recent studies have reported eroded chromatin and cellular identity noise in neurodegenerative diseases such as Alzheimer's. The key questions remain: Is identity noise a driver of aging, or merely a symptom? And if it is the former, can this process be reversed to treat brain aging and neurodegenerative diseases? Our goal is to identify the unique characteristics of ID-loss cells and determine how to retrieve their original identity and specialized functions.
Brain-Body Aging Crosstalk
Restoring brain health by rejuvenating its interconnected organs.
The brain engages in dynamic crosstalk with other organs, suggesting that brain aging could be deeply connected to the youthfulness of these interconnected systems. Our objective is to identify the key organs most closely linked to brain aging and rejuvenate them to indirectly bolster brain function. This strategy revitalizes not just the brain but also overall systemic health and is particularly valuable in cases where direct brain stimulation carries risks, allowing us to safely restore the brain's vitality through the rejuvenation of other organs.
NEXT GENERATION EPIGENTIC REJUVENATION
Investigating mechanisms of epigenetic rejuvenation and developing therapies that restore or stabilize youthful epigenome.
Every cell in our body operates on the same genetic information, yet each cell type maintains its own unique identity and function. This distinction is governed by epigenetic information, encoded in the organization of chromatin, a complex of DNA and proteins. Epigenetic information dictates how each cell type utilizes the genetic code to establish cell state memory and stress resilience. Over time, epigenetic entropy increases, and the specialized epigenetic landscape in each cell type is eroded, a process that drives aging. Fortunately, unlike the fixed nature of the genetic code, epigenetic alterations are much more amenable. Our quest is to pinpoint epigenetic targets of rejuvenation and develop safe, and cost-effective methods to reprogram the epigenome back to its youthful state for revitalizing aged tissues.
EROSION OF CELL IDENTITY
Investigating how cellular identity noise drives aging and whether the identity reset achieves rejuvenation.
​We have uncovered that the developmental program and cell identity undergo erosion over time due to smoothening of the epigenetic landscape, resulting in the loss of tissue function. This concept has gained further traction with recent studies reporting the dual presence of eroded chromatin accessibility and increased cellular identity noise in age-related diseases, such as Alzheimer's disease. The key questions remain: Is the identity noise a driver of aging or merely a symptom of it? And if it is the former, can this process ultimately be reversed to treat aging? Our goal is to understand the features and reversibility of cell identity noise: what are the unique characteristics of ID-loss cells, and how can we retrieve their original identity and specialized functions?
Brain-Body Aging Crosstalk
Rejuvenating organs interconnected with the brain as an integrative treatment strategy.
The brain, an exquisite conductor of the body's symphony, maintains its youthfulness not solely through the health and the vitality of its own cells but also through a complex, dynamic interplay with other vital organs. In this complicated biological network, brain aging is deeply intertwined with youthfulness of these organs. Our goal extends beyond traditional methods; we aim to pinpoint organs tightly linked to brain aging and rejuvenate them for indirectly aiding in recovery of the brain function. This versatile approach improves not just a sinlge organ but systemic health and is crucial in scenarios where direct brain stimulation poses risks, enabling us to safely refresh the brain's youthfulness via other organs.