Research overview

For a long time, it was unclear how animal lifespan and aging are determined, but recent studies using model organisms have shown that lifespan and aging are clearly regulated processes. So far, several molecular mechanisms, so-called lifespan extension pathways such as reduced insulin/IGF-1 signaling, dietary restriction, germline removal and reduced mitochondrial respiration have been identified. Interestingly, an intracellular bulk degradation system, autophagy-lysosomal pathway is commonly activated in all these longevity pathways and its function is critical for lifespan extension (Fig. 1). On the other hand, it has been shown that the activity of the autophagy-lysosomal pathway declines with age, and this is one of main causes for aging and age-related diseases. These findings suggest that this autophagy-lysosomal pathway is a convergent key process to control animal lifespan and ageing. However, many fundamental questions remain unanswered such as its regulatory mechanisms and actual roles in the regulation of lifespan and aging. By utilizing several models such as mammalian cultured cells, yeast (S. cerevisiae), worm (C. elegans) and mice, we aim to uncover the mystery of aging through understanding the molecular and cellular mechanism of autophagy-lysosomal pathway.

On going projects:

  1. Mechanisms of lifespan extension and suppression of aging by the autophagy-lysosomal pathway
  2. Mechanisms of age-related dysfunction of the autophagy-lysosomal pathway
  3. Molecular mechanisms of lysosomal homeostasis and its age-related changes
  4. Molecular mechanisms responsible for the trade-off between reproduction and lifespan

Recent key publications