Evidence for the hallmarks of human aging in replicatively aging yeast

Abstract

Recently, efforts have been made to characterize the hallmarks that accompany and contribute to the phenomenon of aging, as most relevant for humans 1. Remarkably, studying the finite lifespan of the single cell eukaryote budding yeast (recently reviewed in 2 and 3) has been paramount for our understanding of aging. Here, we compile observations from literature over the past decades of research on replicatively aging yeast to highlight how the hallmarks of aging in humans are present in yeast. We find strong evidence for the majority of these, and summarize how yeast aging is especially characterized by the hallmarks of genomic instability, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, and mitochondrial dysfunction.

Poor old pores—The challenge of making and maintaining nuclear pore complexes in aging

“…In general, there is a large degree of conservation of age‐associated changes across different eukaryotic species . To investigate whether NPCs change in similar ways in aging cells and tissues from different species, we extracted data on the abundance of Nups from six published proteome datasets, derived from aging budding yeast , rat , and mouse .…”

“…Yeast has been a powerful model in aging research for many practical reasons . Specifically, for the proteomics studies discussed in this review, the advantages are that the coverage of the Nups is higher in yeast due to the relative simplicity of the proteome.…”

Mechanisms of cellular rejuvenation

“…Among those factors are reactive oxygen species (ROS), carbonylated proteins, protein aggregates, increased cell size, enlarged vacuoles containing decreased pH, mitochondrial fragmentation and decreased membrane potential, enlarged nucleus and nucleolus, accumulation of nuclear pore complexes, decreased levels of histones and altered histone acetylation, loss of silencing and heterozygosity [6,14]. Among those factors are reactive oxygen species (ROS), carbonylated proteins, protein aggregates, increased cell size, enlarged vacuoles containing decreased pH, mitochondrial fragmentation and decreased membrane potential, enlarged nucleus and nucleolus, accumulation of nuclear pore complexes, decreased levels of histones and altered histone acetylation, loss of silencing and heterozygosity [6,14].…”

“…However, in yeast, aging manifests mainly in altered histone acetylation, in humans, age rather correlates with changes in DNA and histone methylation [6,38,39]. However, the sites that are modified are highly variable among species.…”

“…However, the question remains how transferable findings from such model organisms are and whether identified aging factors are indeed contributing to mammalian and human aging. Some major hallmarks of aging, such as epigenetic changes, are shared from yeast to humans; however, the actual sites modified and the involved enzymes appear highly variable [5,6]. Therefore, each aging factor requires careful examination in different organisms.…”