Mre11 deficiency leads to fat body senescence through concurrent dysregulation of mitochondrial function and lipid metabolism

Aging, or organismal senescence, is a gradual decline that begins in adulthood, leading to functional loss and an increased risk of disease. Genomic instability and telomere shortening are primary hallmarks associated with aging. Mre11, crucial for DNA damage repair and telomere maintenance, is a potential biomarker of aging. The silkworm, Bombyx mori, is an ideal model for life science research due to its similarities to humans and experimental advantages (well-annotated genome, short life cycle, and appropriate body size). Mre11 is highly conserved across species. In this study, we embarked on establishing the aging silkworm model and evaluated the etiology. Firstly, we constructed Mre11 homozygous mutants by the CRISPR/Cas9 system. Further examination showed that BmMre11 deficiency successfully induced senescence in the fat body. Furthermore, transcriptome and lipidomics analyses indicated that dysregulation of mitochondrial and lipid metabolism is associated with fat body senescence. This work expands our understanding of Mre11's functions in insect metabolism and aging, offering a promising model for fat body aging research.