Asymmetric Segregation of Age‐Induced Damage in Budding Yeast

Abstract

Cellular damage follows an asymmetric pattern of inheritance in budding yeast. Age‐associated factors accrue in mother cells after each mitotic division, while the ensuing daughter cells are devoid of any damage. Mother cells retain dysfunctional organelles, including oxidised mitochondria, alkaline vacuoles and a nucleus with a weakened permeability barrier. The nucleus of the mother cell contains additional ageing factors such as misfolded proteins, ribosomal DNA (rDNA) circles and fragmented nucleoli. These factors persist throughout replicative ageing and may contribute to cellular senescence. Interestingly, protein aggregates and nucleolar aberrations retained in mitosis are excluded from the meiotic products, also known as gametes. This occurs by a five‐way nuclear division during meiosis II, where the genetic material destined for four gametes is physically separated away from the age‐induced damage through the formation of a fifth nuclear compartment, which eventually gets degraded during gamete maturation. As a result of this specialised nuclear division, meiotic progeny is born young, devoid of any preexisting damage. Key Concepts Age‐induced damage is asymmetrically retained in mother cells during mitosis. Organelle function declines in mother cells as they undergo replicative aging. A diffusion barrier at the bud neck, the region between the mother and daughter cell, facilitates the retention of nuclear and endoplasmic reticulum (ER) age‐induced damage. Age‐induced damage from mother cells is not passed onto the meiotic products. Gametes generated by old mother cells are rejuvenated and have the same replicative lifespan as gametes generated by young mother cells.