Research

Rather than viewing aging solely as a passive accumulation of damage, our research explores the idea that aging may also involve a process of cellular selection. Even in aged tissues, stem cells remain present, yet regenerative capacity is markedly impaired. We propose that repeated stress, injury, and environmental pressures gradually reshape the stem cell pool by preferentially retaining cells with higher survival capacity, even if those cells are not optimally suited for regeneration. We refer to this framework as “cellular survivorship bias” (Science, 2026).

Our work aims to understand when and how this selective process emerges during aging, and which intrinsic and extrinsic factors drive it. Ultimately, our goal is to determine whether the trade-off between survival and regenerative function can be uncoupled. By targeting selection pressures through metabolic modulation, epigenetic reprogramming, and niche normalization, we aim to develop strategies that preserve stem cell resilience while restoring regenerative potential during aging.

Cellular metabolism plays a central role in shaping the epigenetic landscape during aging. Our research investigates how metabolic pathways regulate chromatin states, heterochromatin stability, and gene expression programs in aging stem cells.

Our recent work showed that depletion of the metabolite S-adenosylmethionine (SAM) modulates aging through epigenetic mechanisms (Nature Metabolism, 2024). In parallel, we found that polyamine metabolism influences muscle stem cell aging and activation (Nature Communications, 2025). While these studies establish a functional link between metabolism and stem cell aging, the molecular mechanisms connecting metabolic states to chromatin regulation remain largely unknown.

By studying the metabolism–epigenome axis, we aim to identify key metabolic regulators that shape epigenetic aging programs and uncover molecular targets capable of modulating tissue aging and regeneration.

Building on mechanistic insights, we develop strategies to reverse age-associated cellular decline. Using genetically engineered mouse models that enable muscle stem cell (MuSC)–specific and myofiber-specific expression of Yamanaka factors (Oct4, Sox2, Klf4, and Myc; OSKM), we study how transient reprogramming reshapes epigenetic landscapes and restores youthful cellular states without inducing loss of cell identity. By integrating multi-omics analyses (transcriptomic, epigenomic, and secretomic profiling) with functional regeneration assays, we aim to identify the downstream molecular mediators that drive rejuvenation. 

A central goal of this work is to discover safe and tractable rejuvenation factors that mimic the beneficial effects of reprogramming without requiring direct expression of pluripotency factors. These discoveries aim to establish feasible therapeutic strategies for restoring tissue function and extending functional healthspan.