Autophagy and leucine promote chronological longevity and respiration proficiency during calorie restriction in yeast

Aris, John P.; Alvers, Ashley L.; Ferraiuolo, Roy A.; Fishwick, Laura K.; Hanvivatpong, Amanda; Hu, Doreen; Kirlew, Christine; Leonard, Michael T.; Losin, Kyle J.; Marraffini, Michelle; Seo, Arnold Y.; Swanberg, Veronica; Westcott, Jennifer L.; Wood, Michael S.; Leeuwenburgh, Christiaan; Dunn, William A.

doi:10.1016/j.exger.2013.01.006

Cited by 73 publications

(63 citation statements)

References 70 publications

(96 reference statements)

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“…As in some other studies (9,63,64), we confirmed the activation of autophagy in the early stationary phase (2-day-old cultures). We used GFP-Atg8, which is a marker of both types of macroautophagy, selective and nonselective macroautophagy (14).…”

Section: Fig 11supporting

confidence: 74%

The Stationary-Phase Cells of Saccharomyces cerevisiae Display Dynamic Actin Filaments Required for Processes Extending Chronological Life Span

Vašicová

Lejskova

Malcová

et al. 2015

Molecular and Cellular Biology

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Stationary-growth-phase Saccharomyces cerevisiae yeast cultures consist of nondividing cells that undergo chronological aging. For their successful survival, the turnover of proteins and organelles, ensured by autophagy and the activation of mitochondria, is performed. Some of these processes are engaged in by the actin cytoskeleton. In S. cerevisiae stationary-phase cells, F actin has been shown to form static aggregates named actin bodies, subsequently cited to be markers of quiescence. Our in vivo analyses revealed that stationary-phase cultures contain cells with dynamic actin filaments, besides the cells with static actin bodies. The cells with dynamic actin displayed active endocytosis and autophagy and well-developed mitochondrial networks. Even more, stationary-phase cell cultures grown under calorie restriction predominantly contained cells with actin cables, confirming that the presence of actin cables is linked to successful adaptation to stationary phase. Cells with actin bodies were inactive in endocytosis and autophagy and displayed aberrations in mitochondrial networks. Notably, cells of the respiratory activity-deficient cox4⌬ strain displayed the same mitochondrial aberrations and actin bodies only. Additionally, our results indicate that mitochondrial dysfunction precedes the formation of actin bodies and the appearance of actin bodies corresponds to decreased cell fitness. We conclude that the F-actin status reflects the extent of damage that arises from exponential growth.O nce glucose and other external nutrients are exhausted, cell division stops and Saccharomyces cerevisiae cells are able to survive for extended periods of time. This period of survival has been termed chronological aging and has become a model for aging of postmitotic tissues (1, 2). The cells in these nondividing stationary-phase cell cultures are often termed quiescent (Q) cells (3, 4). Some authors claim that stationary-phase yeast cell populations are heterogeneous and only a portion of them have characteristics of quiescence (5, 6). The ability to survive the period of scarcity of external nutrition and reproduce again upon refeeding is influenced by several life span-extending genetic and environmental interventions. One of the most cited is calorie restriction (CR) (7).In general, cells that are in a nutrient-poor environment activate processes that help them to efficiently utilize inner resources and thus prolong the life span. A catabolic process that has a positive impact on chronological aging is autophagy, which provides nutrients by the vacuolar degradation of damaged or superfluous macromolecules and organelles (8, 9). In addition, Fabrizio et al. demonstrated that the deletion of several genes encoding endosomal functions also shortens the life span (8). Note that some of them have not been directly implicated in autophagy (8). The efficient utilization of resources is ensured by the activation of mitochondrial respiration. It has been proved that the utilization of carbohydrate stores by respiration instead...

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Section: Fig 11supporting

confidence: 74%

The Stationary-Phase Cells of Saccharomyces cerevisiae Display Dynamic Actin Filaments Required for Processes Extending Chronological Life Span

Vašicová

Lejskova

Malcová

et al. 2015

Molecular and Cellular Biology

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“…Thus, autophagy deficiency can lead to TOR inactivation and thereby results in numerous pleiotropic effects. In previous studies, a life-span-prolonging effect originating from TOR inactivation via rapamycin is reported in different organisms 95 - 98 . However, only in a few cases, this increase is unequivocally correlated with Atg genes 99 , 100 .…”

Section: Discussionmentioning

confidence: 90%

Identification of autophagy as a longevity-assurance mechanism in the aging modelPodospora anserina

Knuppertz

Hamann

Pampaloni³

et al. 2014

Autophagy

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The filamentous ascomycete Podospora anserina is a well-established aging model in which a variety of different pathways, including those involved in the control of respiration, ROS generation and scavenging, DNA maintenance, proteostasis, mitochondrial dynamics, and programmed cell death have previously been demonstrated to affect aging and life span. Here we address a potential role of autophagy. We provide data demonstrating high basal autophagy levels even in strains cultivated under noninduced conditions. By monitoring an N-terminal fusion of EGFP to the fungal LC3 homolog PaATG8 over the lifetime of the fungus on medium with and without nitrogen supplementation, respectively, we identified a significant increase of GFP puncta in older and in nitrogen-starved cultures suggesting an induction of autophagy during aging. This conclusion is supported by the demonstration of an age-related and autophagy-dependent degradation of a PaSOD1-GFP reporter protein. The deletion of Paatg1, which leads to the lack of the PaATG1 serine/threonine kinase active in early stages of autophagy induction, impairs ascospore germination and development and shortens life span. Under nitrogen-depleted conditions, life span of the wild type is increased almost 4-fold. In contrast, this effect is annihilated in the Paatg1 deletion strain, suggesting that the ability to induce autophagy is beneficial for this fungus. Collectively, our data identify autophagy as a longevity-assurance mechanism in P. anserina and as another surveillance pathway in the complex network of pathways affecting aging and development. These findings provide perspectives for the elucidation of the mechanisms involved in the regulation of individual pathways and their interactions.

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“…These include chromatin remodeling factors (Dang et al, 2014), maintenance of cellular ATP levels (Choi and Lee, 2013), autophagy and lipid homeostasis (Aris et al, 2013; Lester et al, 2013; Richard et al, 2013), rDNA replication (Kwan et al, 2013), nitric oxide (Li et al, 2011), and glutathione and redox homeostasis (Mannarino et al, 2008; Molin et al, 2011), among others. The relationship of each of these to the established longevity mechanisms and to each other will require additional study.…”

Section: Dietary Restriction In S Cerevisiaementioning

confidence: 99%

Dietary restriction and lifespan: Lessons from invertebrate models

Kapahi

Kaeberlein

Hansen

2017

Ageing Research Reviews

310

217

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Dietary restriction (DR) is the most robust environmental manipulation known to increase active and healthy lifespan in many species. Despite differences in the protocols and the way DR is carried out in different organisms, conserved relationships are emerging among multiple species. Elegant studies from numerous model organisms are further defining the importance of various nutrient-signaling pathways including mTOR (mechanistic target of rapamycin), insulin/IGF-1-like signaling and sirtuins in mediating the effects of DR. We here review current advances in our understanding of the molecular mechanisms altered by DR to promote lifespan in three major invertebrate models, the budding yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans, and the fruit fly Drosophila melanogaster.

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Autophagy and leucine promote chronological longevity and respiration proficiency during calorie restriction in yeast

Cited by 73 publications

References 70 publications

The Stationary-Phase Cells of Saccharomyces cerevisiae Display Dynamic Actin Filaments Required for Processes Extending Chronological Life Span

The Stationary-Phase Cells of Saccharomyces cerevisiae Display Dynamic Actin Filaments Required for Processes Extending Chronological Life Span

Identification of autophagy as a longevity-assurance mechanism in the aging modelPodospora anserina

Dietary restriction and lifespan: Lessons from invertebrate models

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