Abstract:Recent studies have revealed the role of actin dynamics in the regulation of yeast aging. Although the target of rapamycin (TOR) complex, serine/threonine kinase Sch9, and Ras2 have been shown to play important roles in aging for a long time, the relationship between these regulators and actin has not yet been reported. In this study we investigated the roles of actin polarization in tor1Δ, sch9Δ, and ras2Δ mutant cells. We found that the actin structures in tor1Δ, sch9Δ, and ras2Δ mutant cells were more dynam… Show more
“…Furthermore, there are several genes encoding motor proteins called nuclear myosins [36][37][38]. Knockdown of nuclear myosin I-β (NM1β) or the presence of jaspakinolide [39,40], which stabilizes actin polymers, inhibits the repositioning of chromosomes [33]. Although more research is required to pin down exactly how these molecules are involved, observations (as well as those from the analysis of sub-chromosomal reorganization) strongly indicate that nuclear actin and myosin play a major role in chromosome territory dynamics.…”
Section: Heterochromatin Versus Euchromatinmentioning
Background: Our daily intake of food provides nutrients for the maintenance of health, growth and development. The field of nutrigenomics aims to link dietary intake/nutrients to changes in epigenetic status and gene expression.
Summary: Although the relationship between our diet and our genes in under intense investigation, there is still as significant aspect of our genome that have received little attention with regards to this. In the past 15 years the importance of genome organization has become increasingly evident, with research identifying small scale local changes to large segments of the genome dynamically repositioning within the nucleus in response to/or mediating change in gene expression. The discovery of these dynamic processes and organization maybe as significant as dynamic plate tectonics is to geology, there is little information tying genome organization to specific nutrients or dietary intake.
Key Messages: Here we detail key principles of genome organization and structure, with emphasis on genome folding and organization, and link how these contribute to our future understand of nutrigenomics.
“…Furthermore, there are several genes encoding motor proteins called nuclear myosins [36][37][38]. Knockdown of nuclear myosin I-β (NM1β) or the presence of jaspakinolide [39,40], which stabilizes actin polymers, inhibits the repositioning of chromosomes [33]. Although more research is required to pin down exactly how these molecules are involved, observations (as well as those from the analysis of sub-chromosomal reorganization) strongly indicate that nuclear actin and myosin play a major role in chromosome territory dynamics.…”
Section: Heterochromatin Versus Euchromatinmentioning
Background: Our daily intake of food provides nutrients for the maintenance of health, growth and development. The field of nutrigenomics aims to link dietary intake/nutrients to changes in epigenetic status and gene expression.
Summary: Although the relationship between our diet and our genes in under intense investigation, there is still as significant aspect of our genome that have received little attention with regards to this. In the past 15 years the importance of genome organization has become increasingly evident, with research identifying small scale local changes to large segments of the genome dynamically repositioning within the nucleus in response to/or mediating change in gene expression. The discovery of these dynamic processes and organization maybe as significant as dynamic plate tectonics is to geology, there is little information tying genome organization to specific nutrients or dietary intake.
Key Messages: Here we detail key principles of genome organization and structure, with emphasis on genome folding and organization, and link how these contribute to our future understand of nutrigenomics.
“…In JunQ and INQ misfolded proteins are refolded, while those deposited in IPOD probably await clearance via autophagy 146 147 . This partitioning requires Hsp104 and functional actin cables 148 149 150 , the latter being another essential lifespan determinant 151 152 . Partitioning of misfolded proteins is beneficial during chronological ageing 153 and assures the asymmetric inheritance of damaged and non-functional proteins during replicative ageing, thereby producing rejuvenated daughter cells 148 149 150 .…”
Section: Ph Control Stress Tolerance and Longevitymentioning
The plasma membrane H+-ATPase Pma1 and the vacuolar V-ATPase act in close harmony to tightly control pH homeostasis, which is essential for a vast number of physiological processes. As these main two regulators of pH are responsive to the nutritional status of the cell, it seems evident that pH homeostasis acts in conjunction with nutrient-induced signalling pathways. Indeed, both PKA and the TORC1-Sch9 axis influence the proton pumping activity of the V-ATPase and possibly also of Pma1. In addition, it recently became clear that the proton acts as a second messenger to signal glucose availability via the V-ATPase to PKA and TORC1-Sch9. Given the prominent role of nutrient signalling in longevity, it is not surprising that pH homeostasis has been linked to ageing and longevity as well. A first indication is provided by acetic acid, whose uptake by the cell induces toxicity and affects longevity. Secondly, vacuolar acidity has been linked to autophagic processes, including mitophagy. In agreement with this, a decline in vacuolar acidity was shown to induce mitochondrial dysfunction and shorten lifespan. In addition, the asymmetric inheritance of Pma1 has been associated with replicative ageing and this again links to repercussions on vacuolar pH. Taken together, accumulating evidence indicates that pH homeostasis plays a prominent role in the determination of ageing and longevity, thereby providing new perspectives and avenues to explore the underlying molecular mechanisms.
“…This effect, known as caloric restriction, can be nullified by methionine supplementation [ 34 ]. Similarly, mutations that affect signal transduction pathways can lead to improper sensing of environmental resources [ 35 ], resulting in similar outcomes. However, despite identifying some mutations in the cellular background or environmental conditions that might influence aging speed, we still do not know the real factor that limits/determines cell lifespan.…”
Aging is inevitable and affects all cell types, thus yeast cells are often used as a model in aging studies. There are two approaches to studying aging in yeast: replicative aging, which describes the proliferative potential of cells, and chronological aging, which is used for studying post-mitotic cells. While analyzing the chronological lifespan (CLS) of diploid
Saccharomyces cerevisiae
cells, we discovered a remarkable phenomenon: ploidy reduction during aging progression. To uncover the mechanism behind this unusual process we used yeast strains undergoing a CLS assay, looking for various aging parameters. Cell mortality, regrowth ability, autophagy induction and cellular DNA content measurements indicated that during the CLS assay, dying cells lost their DNA, and only diploids survived. We demonstrated that autophagy was responsible for the gradual loss of DNA. The nucleophagy marker activation at the start of the CLS experiment correlated with the significant drop in cell viability. The activation of piecemeal microautophagy of nucleus (PMN) markers appeared to accompany the chronological aging process until the end. Our findings emphasize the significance of maintaining at least one intact copy of the genome for the survival of post-mitotic diploid cells. During chronological aging, cellular components, including DNA, are exposed to increasing stress, leading to DNA damage and fragmentation in aging cells. We propose that PMN-dependent clearance of damaged DNA from the nucleus helps prevent genome rearrangements. However, as long as one copy of the genome can be rebuilt, cells can still survive.
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