Abstract:

Since the risk of infertility and chromosome aberrations increases with age, elucidating the mechanism behind it is an important biological and social issue. The increased risk is often explained by “aging”, however, what age-related changes in germline cells exactly cause the problem is not well understood. Chromosome translocations in germline cells can cause miscarriages, infertility, and serious diseases across generations. Our research has focused on how chromosomal translocations occur and revealed that a disruption of the special DNA repair mechanisms associated with transcription causes chromosomal translocations (1,2). Furthermore, we discovered nucleolar condensates formed upon stresses, such as transcription inhibition, UV irradiation, anticancer drugs, and cold shock. These condensates involve many genomic loci and increase chromosomal translocations between them (3). Given that Robertsonian translocations involving acrocentric chromosomes localized in the nucleolus are common in germline cells, transcriptional and nucleolar stress in germline cells plays a role in mediating chromosome translocations. In this talk, I will introduce our attempt to redefine the phenomenon previously vaguely referred to as “aging” in germline cells to explain the specific age-related changes that lead to chromosomal translocations and to discuss the future direction of aging research.

1. Yasuhara et al. Cell 175(2):558-570 (2018)

2. Yasuhara et al. Cell Rep 38(5):110335 (2022)

3. Yasuhara et al. Mol Cell 82(15):2738-2753 (2022)