Linking cell polarity, aging and rejuvenation (original) (raw)
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Yeast mother cell-specific ageing, genetic (in)stability, and the somatic mutation theory of ageing
Nucleic Acids Research, 2007
Yeast mother cell-specific ageing is characterized by a limited capacity to produce daughter cells. The replicative lifespan is determined by the number of cell cycles a mother cell has undergone, not by calendar time, and in a population of cells its distribution follows the Gompertz law. Daughter cells reset their clock to zero and enjoy the full lifespan characteristic for the strain. This kind of replicative ageing of a cell population based on asymmetric cell divisions is investigated as a model for the ageing of a stem cell population in higher organisms. The simple fact that the daughter cells can reset their clock to zero precludes the accumulation of chromosomal mutations as the cause of ageing, because semiconservative replication would lead to the same mutations in the daughters. However, nature is more complicated than that because, (i) the very last daughters of old mothers do not reset the clock; and (ii) mutations in mitochondrial DNA could play a role in ageing due to the large copy number in the cell and a possible asymmetric distribution of damaged mitochondrial DNA between mother and daughter cell. Investigation of the loss of heterozygosity in diploid cells at the end of their mother cell-specific lifespan has shown that genomic rearrangements do occur in old mother cells. However, it is not clear if this kind of genomic instability is causative for the ageing process. Damaged material other than DNA, for instance misfolded, oxidized or otherwise damaged proteins, seem to play a major role in ageing, depending on the balance between production and removal through various repair processes, for instance several kinds of proteolysis and autophagy. We are reviewing here the evidence for genetic change and its causality in the mother cell-specific ageing process of yeast.
A mechanism for asymmetric segregation of age during yeast budding
Nature, 2008
Ageing and the mortality that ensues are sustainable for the species only if age is reset in newborns. In budding yeast, buds are made young whereas ageing factors, such as carbonylated proteins and DNA circles, remain confined to the ageing mother cell. The mechanisms of this confinement and their relevance are poorly understood. Here we show that a septin-dependent, lateral diffusion barrier forms in the nuclear envelope and limits the translocation of pre-existing nuclear pores into the bud. The retention of DNA circles within the mother cell depends on the presence of the diffusion barrier and on the anchorage of the circles to pores mediated by the nuclear basket. In accordance with the diffusion barrier ensuring the asymmetric segregation of nuclear age-determinants, the barrier mutant bud6D fails to properly reset age in buds. Our data involve septin-dependent diffusion barriers in the confinement of ageing factors to one daughter cell during asymmetric cell division.
Aging and differentiation in yeast populations: elders with different properties and functions
FEMS Yeast Research, 2013
Over the past decade, it has become evident that similarly to cells forming metazoan tissues, yeast cells have the ability to differentiate and form specialized cell types. Examples of yeast cellular differentiation have been identified both in yeast liquid cultures and within multicellular structures occupying solid surfaces. Most current knowledge on different cell types comes from studies of the spatiotemporal internal architecture of colonies developing on various media. With a few exceptions, yeast cell differentiation often concerns nongrowing, stationary-phase cells and leads to the formation of cell subpopulations differing in stress resistance, cell metabolism, respiration, ROS production, and others. These differences can affect longevity of particular subpopulations. In contrast to liquid cultures, where various cell types are dispersed within stationary-phase populations, cellular differentiation depends on the specific position of particular cells within multicellular colonies. Differentiated colonies, thus, resemble primitive multicellular organisms, in which the gradients of certain compounds and the position of cells within the structure affect cellular differentiation. In this review, we summarize and compare the properties of diverse types of differentiated chronologically aging yeast cells that have been identified in colonies growing on different media, as well as of those found in liquid cultures. **(according to Peters et al. (2012).
Fission Yeast and Other Yeasts as Emergent Models to Unravel Cellular Aging in Eukaryotes
Journals of Gerontology Series A-biological Sciences and Medical Sciences, 2010
In the past years, simple organisms such as yeasts and worms have contributed a great deal to aging research. Studies pioneered in Saccharomyces cerevisiae were useful to elucidate a signifi cant number of molecular mechanisms underlying cellular aging and to discover novel longevity genes. Importantly, these genes proved many times to be conserved in multicellular eukaryotes. Consequently, such discovery approaches are being extended to other yeast models, such as Schizosaccharomyces pombe , Candida albicans , Kluyveromyces lactis , and Cryptococcus neoformans . In fi ssion yeast, researchers have found links between asymmetrical cell division and nutrient signaling pathways with aging. In this review, we discuss the state of knowledge on the mechanisms controlling both replicative and chronological aging in S pombe and the other emergent yeast models.
Nature Cell Biology, 2010
Cellular aging is known to correlate with the accumulation of many harmful agents1, but can aging also result from deterioration of certain poorly-renewed beneficial components? Here we found that a group of plasma membrane-associated transporters, belonging to the multidrug resistance (MDR) protein families, may represent the latter type aging determinants. These proteins are deposited before the birth of a virgin yeast cell. During the subsequent division of this cell, the original protein population remains tightly associated with the mother cortex, while the newly synthesized transporter proteins are deposited mostly into the bud. Thus, the new and old pools of membrane-bound MDR proteins are spatially segregated during yeast asymmetric cell division with the older pool stably inherited by the aging mother. A model based on the observed dynamics of MDR protein inheritance and turnover predicted a decline in MDR activity as the mother cell advances in replicative age. As MDR proteins play crucial roles in cellular metabolism, detoxification and stress response, their collective decline may lead to fitness loss at an advance age. Supporting this hypothesis, mutants lacking certain MDR genes exhibited a reduced replicative lifespan (RLS), while introduction of only one extra copy of these MDR genes extended RLS.
Oncotarget
We propose a hypothesis of a mechanism linking cellular aging to cellular quiescence in chronologically aging budding yeast. Our hypothesis posits that this mechanism integrates four different processes, all of which are initiated after yeast cells cultured in a medium initially containing glucose consume it. Quiescent cells that develop in these cultures can be separated into the high-and low-density subpopulations of different buoyant densities. Process 1 of the proposed mechanism consists of a cell-cycle arrest in the G 1 phase and leads to the formation of highdensity quiescent cells. Process 2 results in converting high-density quiescent cells into low-density quiescent cells. Processes 3 and 4 cause a fast or slow decline in the quiescence of low-or high-density quiescent cells, respectively. Here, we tested our hypothesis by assessing how four different geroprotectors influence the four processes that could link cellular aging to cellular quiescence. We found that these geroprotectors differently affect processes 1 and 2 and decelerate processes 3 and 4. We also found that a rise in trehalose within quiescent yeast contributes to chronological aging and quiescence maintenance. These data collectively provide conclusive evidence for a mechanistic link between cellular aging and cellular quiescence.
Frontiers in genetics, 2016
Studies employing the budding yeast Saccharomyces cerevisiae as a model organism have provided deep insights into molecular mechanisms of cellular and organismal aging in multicellular eukaryotes and have demonstrated that the main features of biological aging are evolutionarily conserved. Aging in S. cerevisiae is studied by measuring replicative or chronological lifespan. Yeast replicative aging is likely to model aging of mitotically competent human cell types, while yeast chronological aging is believed to mimic aging of post-mitotic human cell types. Emergent evidence implies that various organelle-organelle and organelle-cytosol communications play essential roles in chronological aging of S. cerevisiae. The molecular mechanisms underlying the vital roles of intercompartmental communications in yeast chronological aging have begun to emerge. The scope of this review is to critically analyze recent progress in understanding such mechanisms. Our analysis suggests a model for how...