Heat stress promotes longevity in budding yeast by relaxing the confinement of age-promoting factors in the mother cell

Baldi, Sandro; Bolognesi, Alessio; Meinema, Anne C; Barral, Yves

doi:10.7554/elife.28329

Cited by 30 publications

(28 citation statements)

References 93 publications

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“…In the FNDs, other particles or molecules only leak into the daughter cells if they detach from the membrane in the mother cells or if the diffusion barrier becomes permeable [19]. This mechanism is in place to protect daughter cells from harmful substances like aging factors [20].…”

Section: Introductionmentioning

confidence: 99%

The Fate of Lipid-Coated and Uncoated Fluorescent Nanodiamonds during Cell Division in Yeast

et al. 2020

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Fluorescent nanodiamonds are frequently used as biolabels. They have also recently been established for magnetic resonance and temperature sensing at the nanoscale level. To properly use them in cell biology, we first have to understand their intracellular fate. Here, we investigated, for the first time, what happens to diamond particles during and after cell division in yeast (Saccharomyces cerevisiae) cells. More concretely, our goal was to answer the question of whether nanodiamonds remain in the mother cells or end up in the daughter cells. Yeast cells are widely used as a model organism in aging and biotechnology research, and they are particularly interesting because their asymmetric cell division leads to morphologically different mother and daughter cells. Although yeast cells have a mechanism to prevent potentially harmful substances from entering the daughter cells, we found an increased number of diamond particles in daughter cells. Additionally, we found substantial excretion of particles, which has not been reported for mammalian cells. We also investigated what types of movement diamond particles undergo in the cells. Finally, we also compared bare nanodiamonds with lipid-coated diamonds, and there were no significant differences in respect to either movement or intracellular fate.

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Section: Introductionmentioning

confidence: 99%

The Fate of Lipid-Coated and Uncoated Fluorescent Nanodiamonds during Cell Division in Yeast

et al. 2020

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“…Furthermore, heat, irradiation, and oxidative stress have all been shown to extend lifespan in yeast, fruit fly, nematodes, and rodents [ 8 – 12 ], suggesting that similar pathways are involved in regulation of longevity across organisms [ 12 ]. Hormetic effects of heat shock on lifespan extension have been associated with increased transcription of chaperone coding genes, as well as with activation of autophagy and opening of the nuclear envelope [ 8 , 11 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Given its “cross-modal” nature as well as the variety of triggers and cell responses elicited, hormesis can be considered as a complex phenomenon. Thus, although extensively studied [ 8 , 12 ], the exact mechanisms contributing to heat shock-mediated lifespan extension in yeast still remain to be uncovered. Here, we found that a metabolic switch from glycolysis to aerobic respiration, and the resulting increase in the reactive oxygen species (ROS) levels trigger the activation of the pentose phosphate pathway (PPP) in budding yeast Saccharomyces cerevisiae cells undergoing mild HS.…”

Section: Introductionmentioning

confidence: 99%

Heat-induced longevity in budding yeast requires respiratory metabolism and glutathione recycling

Musa

Perić

Dib

et al. 2018

Aging

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Heat-induced hormesis is a well-known conserved phenomenon in aging, traditionally attributed to the benefits conferred by increased amounts of heat shock (HS) proteins. Here we find that the key event for the HS-induced lifespan extension in budding yeast is the switch from glycolysis to respiratory metabolism. The resulting increase in reactive oxygen species activates the antioxidant response, supported by the redirection of glucose from glycolysis to the pentose phosphate pathway, increasing the production of NADPH. This sequence of events culminates in replicative lifespan (RLS) extension, implying decreased mortality per generation that persists even after the HS has finished. We found that switching to respiratory metabolism, and particularly the consequent increase in glutathione levels, were essential for the observed RLS extension. These results draw the focus away solely from the HS response and demonstrate that the antioxidant response has a key role in heat-induced hormesis. Our findings underscore the importance of the changes in cellular metabolic activity for heat-induced longevity in budding yeast.

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“…By analyzing pathways regulated by metformin at distinct age points, we detected a rapid activation of adaptive stress responses and longevity assurance pathways such as downregulation of the ribosome (MacInnes, 2016) and induction of oxidative stress response (Honda and Honda, 1999), immune response (Xia et al, 2019) and heat stress response (Baldi et al, 2017) in young animals (Figure 5C-E and S9C). General autophagy (Hansen et al, 2018) was also comparably regulated albeit to a smaller extent (Figure S9D).…”

Section: Resultsmentioning

confidence: 99%

Late life metformin treatment limits cell survival and shortens lifespan by triggering an aging-associated failure of energy metabolism

Espada

Dakhovnik

Chaudhari

et al. 2019

Preprint

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18The diabetes drug metformin is to be clinically tested in aged humans to achieve health 19 span extension, but little is known about responses of old non-diabetic individuals to this 20 drug. By in vitro and in vivo tests we found that metformin shortens life span and limits 21 cell survival when provided in late life, contrary to its positive early life effects. 22 Mechanistically, metformin exacerbates aging-associated mitochondrial dysfunction 23 towards respiratory failure, aggravated by the inability of old cells to upregulate 24 glycolysis in response to metformin, leading to ATP exhaustion. The beneficial dietary 25 restriction effect of metformin on lipid reserves is abrogated in old animals, contributing 26 to metabolic failure, while ectopic stabilization of cellular ATP levels alleviates late life 27 metformin toxicity in vitro and in vivo. The toxicity is also suspended in nematodes 28 carrying diabetes-like insulin receptor insufficiency and showing prolonged resilience to 29 metabolic stress induced by metformin. In sum, we uncovered an alarming metabolic 30 decay triggered by metformin in late life which may limit its benefits for non-diabetic 31 elderly patients. Novel regulators of life extension by metformin are also presented. 32 33 Keywords 34 Aging, metformin, mitochondrial dysfunction, glycolysis, dietary restriction, ATP 35 exhaustion, protein kinase A 36 37 Highlights 38  Late life metformin treatment limits cell survival and shortens lifespan. 39  Metformin exacerbates aging-associated mitochondrial dysfunction causing fatal 1 ATP exhaustion. 2  Old cells fail to upregulate glycolysis as a compensatory response to metformin. 3  The dietary restriction (DR) mimetic response to metformin is abrogated in old 4 animals. 5  PKA and not AMPK pathway instigates the early life DR response to metformin. 6  Stabilization of cellular ATP levels alleviates late life metformin toxicity in vitro 7 and in vivo.8 9 12 (Salani et al., 2014). Metformin is thought to act by inhibiting mitochondrial respiration 13 (Wheaton et al., 2014). Recently, metformin was tested for additional physiological 14 effects and found to extend life span in animal models ranging from nematodes to mice 15 (Martin-Montalvo et al., 2013; Onken and Driscoll, 2010). Extensive clinical use in 16 humans enabled the collection and analysis of data on the longevity of human diabetes 17 patients treated with metformin. The metformin-exposed diabetes cohort was found to 18 be longer lived than untreated healthy subjects (Bannister et al., 2014), in line with 19 potential life-prolonging properties of metformin. 20 Type 2 diabetes is an aging-associated disorder and many patients start 21 metformin treatment in late life. Based on survival analysis of diabetes patients, it was 22proposed that life prolonging effects of metformin may extend also to metabolic-healthy 23 elderly individuals. Considering moderate metformin side effects in diabetes and the 24 potential healthy aging benefits, metformin has emerged as an attracti...

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Heat stress promotes longevity in budding yeast by relaxing the confinement of age-promoting factors in the mother cell

Cited by 30 publications

References 93 publications

The Fate of Lipid-Coated and Uncoated Fluorescent Nanodiamonds during Cell Division in Yeast

The Fate of Lipid-Coated and Uncoated Fluorescent Nanodiamonds during Cell Division in Yeast

Heat-induced longevity in budding yeast requires respiratory metabolism and glutathione recycling

Late life metformin treatment limits cell survival and shortens lifespan by triggering an aging-associated failure of energy metabolism

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