Independent regulation of age associated fat accumulation and longevity

Beas, Anthony; Gordon, Patricia B.; Prentiss, Clara L.; Olsen, Carissa Perez; Kukurugya, Matthew A.; Bennett, Bryson D.; Parkhurst, Susan M.; Gottschling, Daniel E.

doi:10.1038/s41467-020-16358-7

Cited by 28 publications

(25 citation statements)

References 44 publications

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“…, numbers and size of vacuoles, or numbers of lipid droplets. The lipid droplets become more prevalent in aged cells, confirming previous findings ( Beas et al, 2020 ; Figure 4—figure supplement 3 ). In almost all cells, especially the vacuoles take up a larger fraction of the cell volume than they do in young cells.…”

Section: Resultssupporting

confidence: 90%

A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast

Mouton

Thaller

Crane

et al. 2020

eLife

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Cellular aging is a multifactorial process that is characterized by a decline in homeostatic capacity, best described at the molecular level. Physicochemical properties such as pH and macromolecular crowding are essential to all molecular processes in cells and require maintenance. Whether a drift in physicochemical properties contributes to the overall decline of homeostasis in aging is not known. Here we show that the cytosol of yeast cells acidifies modestly in early aging and sharply after senescence. Using a macromolecular crowding sensor optimized for long-term FRET measurements, we show that crowding is rather stable and that the stability of crowding is a stronger predictor for lifespan than the absolute crowding levels. Additionally, in aged cells we observe drastic changes in organellar volume, leading to crowding on the µm scale, which we term organellar crowding. Our measurements provide an initial framework of physicochemical parameters of replicatively aged yeast cells.

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Section: Resultssupporting

confidence: 90%

A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast

Mouton

Thaller

Crane

et al. 2020

eLife

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“…MFRTA claims that ROS levels dramatically increase with aging and react with organic components of the cell, including DNA, proteins and lipids. In line with this, stress as well as aging induces the accumulation of LDs in yeast and mammalian cells [135][136][137]. There is growing evidence that LDs play a role in the regulation of longevity [138].…”

Section: The Function Of Lds In Modulating Stressmentioning

confidence: 70%

“…LDs may also affect longevity in mammals, as they can activate the sirtuin SIRT1. In many studies and in many model organisms, activation of this enzyme leads to a prolonged life, improved organ functions, a higher fitness and increased stress and disease resistance [135].…”

Section: Emergence and Role Of Lds During Agingmentioning

confidence: 99%

Friend or Foe: Lipid Droplets as Organelles for Protein and Lipid Storage in Cellular Stress Response, Aging and Disease

et al. 2020

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Lipid droplets (LDs) were considered as a mere lipid storage organelle for a long time. Recent evidence suggests that LDs are in fact distinct and dynamic organelles with a specialized proteome and functions in many cellular roles. As such, LDs contribute to cellular signaling, protein and lipid homeostasis, metabolic diseases and inflammation. In line with the multitude of functions, LDs interact with many cellular organelles including mitochondria, peroxisomes, lysosomes, the endoplasmic reticulum and the nucleus. LDs are highly mobile and dynamic organelles and impaired motility disrupts the interaction with other organelles. The reduction of interorganelle contacts results in a multitude of pathophysiologies and frequently in neurodegenerative diseases. Contacts not only supply lipids for β-oxidation in mitochondria and peroxisomes, but also may include the transfer of toxic lipids as well as misfolded and harmful proteins to LDs. Furthermore, LDs assist in the removal of protein aggregates when severe proteotoxic stress overwhelms the proteasomal system. During imbalance of cellular lipid homeostasis, LDs also support cellular detoxification. Fine-tuning of LD function is of crucial importance and many diseases are associated with dysfunctional LDs. We summarize the current understanding of LDs and their interactions with organelles, providing a storage site for harmful proteins and lipids during cellular stress, aging inflammation and various disease states.

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“…As a neurotransmitter, serotonin is involved in the regulation of the central nervous system, the cardiovascular system, and many other processes in the body ( Berger et al, 2009 ), while melatonin affects a range of phenotypes including oxidative stress response, mitochondrial metabolism ( Reiter et al, 2018 ), and circadian rhythms ( Emens and Burgess, 2015 ). Moreover, a recent study in yeast showed that overexpression of BNA2 ( BNA2 -oe) increased flux through the TRP-producing shikimate/aromatic amino acid biosynthesis pathways, leading to reduced lipid droplet formation in aging cells due to depletion of necessary precursors ( Beas et al, 2020 ). Interestingly this study also showed that BNA2- oe-induced life span extension and reduced lipid droplet formation is independent of NAD + production.…”

Section: Immunity Kyn Pathway Metabolites and De Novo Nad + Metabolismmentioning

confidence: 99%

NAD+ Metabolism, Metabolic Stress, and Infection

Groth

Venkatakrishnan

Lin

2021

Front. Mol. Biosci.

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Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite with wide-ranging and significant roles in the cell. Defects in NAD+ metabolism have been associated with many human disorders; it is therefore an emerging therapeutic target. Moreover, NAD+ metabolism is perturbed during colonization by a variety of pathogens, either due to the molecular mechanisms employed by these infectious agents or by the host immune response they trigger. Three main biosynthetic pathways, including the de novo and salvage pathways, contribute to the production of NAD+ with a high degree of conservation from bacteria to humans. De novo biosynthesis, which begins with l-tryptophan in eukaryotes, is also known as the kynurenine pathway. Intermediates of this pathway have various beneficial and deleterious effects on cellular health in different contexts. For example, dysregulation of this pathway is linked to neurotoxicity and oxidative stress. Activation of the de novo pathway is also implicated in various infections and inflammatory signaling. Given the dynamic flexibility and multiple roles of NAD+ intermediates, it is important to understand the interconnections and cross-regulations of NAD+ precursors and associated signaling pathways to understand how cells regulate NAD+ homeostasis in response to various growth conditions. Although regulation of NAD+ homeostasis remains incompletely understood, studies in the genetically tractable budding yeast Saccharomyces cerevisiae may help provide some molecular basis for how NAD+ homeostasis factors contribute to the maintenance and regulation of cellular function and how they are regulated by various nutritional and stress signals. Here we present a brief overview of recent insights and discoveries made with respect to the relationship between NAD+ metabolism and selected human disorders and infections, with a particular focus on the de novo pathway. We also discuss how studies in budding yeast may help elucidate the regulation of NAD+ homeostasis.

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Independent regulation of age associated fat accumulation and longevity

Cited by 28 publications

References 44 publications

A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast

A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast

Friend or Foe: Lipid Droplets as Organelles for Protein and Lipid Storage in Cellular Stress Response, Aging and Disease

NAD+ Metabolism, Metabolic Stress, and Infection

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