Human centenarian–associated SIRT6 mutants modulate hepatocyte metabolism and collagen deposition in multilineage hepatic 3D spheroids

Fröhlich, Jan; Raffaele, Marco; Skálová, Helena; Leire, Eric; Pata, Illar; Pata, Pille; Gorbunova, Vera; Vinciguerra, Manlio

doi:10.1007/s11357-022-00713-1

Cited by 5 publications

(4 citation statements)

References 77 publications

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“…Another group of important nutrient sensors is sirtuins (de Lucia et al, 2020;Fusco et al, 2012), which have already been mentioned in relation to epigenetic and genome stability as regulators of lifespan (Frohlich et al, 2023;Taylor et al, 2022;Tombline et al, 2020) As a nutrient sensor regulated by sirtuins, also downstream of AMPK (J. H. Jeong et al, 2023) and insulin/IGF-1 signaling, the FOXOs transcription factors are implicated in the complex nutrient-sensing network (Sanchez et al, 2023). For example, genetic variations in the IGF-1 pathway, particularly in FOXO3, have been associated with human longevity in several cohorts (Flachsbart et al, 2017).…”

Section: Loss Of Proteostasismentioning

confidence: 99%

“…The NAD + ‐dependent histone deacetylases from the sirtuin family have been identified as crucial transcription factors involved in various signaling pathways related to DDR, thus associated with longevity in humans and model organisms (Flachsbart et al., 2017; Frankum et al., 2022; Frohlich et al., 2023; Taylor et al., 2022; X. Tian et al., 2019; Tombline et al., 2020). Sirtuin‐6, as a member of the SIRTs family, promotes genomic stability through DSBs repair mechanisms and acts as a sensor for DNA damage along with PARP1, meiotic recombination 11 homolog 1, and Ku80 protein (Yu Chen et al., 2019; Onn et al., 2020; X. Tian et al., 2019; Van Meter et al., 2016; G. Yang et al., 2018).…”

Section: “Old” Hallmarks Of Aging—longevity Perspectivementioning

confidence: 99%

“…Furthermore, the centenarian allele of SIRT6 , known as centSIRT6 , has been shown to strongly interact with the nuclear scaffold protein lamin A/C, ultimately resulting in better genome maintenance and increased longevity (Simon et al., 2022). Many theories have been suggested to explain the lifespan‐extending effects of SIRT6, including an improvement in glucose metabolism and the restoration of energy homeostasis (Frohlich et al., 2023). Mechanistically, SIRT6 elevates de novo NAD + synthesis gluconeogenesis in aged mice via upregulation of genes involved in hepatic mitochondrial catabolic and anti‐inflammatory pathways (Roichman et al., 2021).…”

Section: “Old” Hallmarks Of Aging—longevity Perspectivementioning

confidence: 99%

See 2 more Smart Citations

Nurturing longevity through natural compounds: Where do we stand, and where do we go?

Todorova,

Savova,

Mihaylova

et al. 2024

Food Frontiers

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The revolution in aging research through the past decade has driven the progress in interventions that promote longevity. Dissection of the “old” hallmarks of aging has provided solid data for the definition of at least three “new” ones, opening avenues for the development of novel hallmark‐targeted pro‐longevity approaches. The quest for geroprotectors is of enormous interest with the ultimate goal of finding the alchemical stone that induces healthy aging and increases lifespan, pushing the limits of human longevity or even uncovering the absence of such limits. Several of the well‐appreciated geroprotectors that are recognized as longevity promoters are of natural origin such as metformin, resveratrol, aspirin, and spermidine. As the search for pharmacological modulators of healthspan and lifespan continues, numerous studies are focusing on the potential of plant secondary metabolites. The current review attempts to critically assess the available interventions and the breakthrough discoveries in the field of longevity research over the past decade. Correspondingly, novel approaches targeting the hallmarks of aging have been outlined, and the future goals in longevity research have been enlightened. Special emphasis has been placed on the potential of plant‐derived compounds as pro‐longevity agents.

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Section: Loss Of Proteostasismentioning

confidence: 99%

Section: “Old” Hallmarks Of Aging—longevity Perspectivementioning

confidence: 99%

Section: “Old” Hallmarks Of Aging—longevity Perspectivementioning

confidence: 99%

See 1 more Smart Citation

Nurturing longevity through natural compounds: Where do we stand, and where do we go?

Todorova,

Savova,

Mihaylova

et al. 2024

Food Frontiers

View full text Add to dashboard Cite

show abstract

“…This centSIRT6 is also beneficial in preventing nonalcoholic liver disease such as steatohepatitis. Overexpression of centSIRT6 resulted in a dramatic change in the metabolome and secretome of immortalized human hepatocytes, with an increase of most amino acids, unsaturated fatty acids, and glycerophospholipids and decreased ceramide (Frohlich et al, 2023). Notably, recent studies have shown that the devastating phenotypes of Sirt6 −/− mice could be alleviated by a high-fat diet (HFD).…”

Section: Positive Roles In Lifespan and Longevitymentioning

confidence: 99%

The many faces of SIRT6 in the retina and retinal pigment epithelium

Cheng,

Keuthan,

Esumi

2023

Front. Cell Dev. Biol.

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Sirtuin 6 (SIRT6) is a member of the mammalian sirtuin family of NAD+-dependent protein deacylases, homologues of the yeast silent information regulator 2 (Sir2). SIRT6 has remarkably diverse functions and plays a key role in a variety of biological processes for maintaining cellular and organismal homeostasis. In this review, our primary aim is to summarize recent progress in understanding SIRT6’s functions in the retina and retinal pigment epithelium (RPE), with the hope of further drawing interests in SIRT6 to increase efforts in exploring the therapeutic potential of this unique protein in the vision field. Before describing SIRT6’s role in the eye, we first discuss SIRT6’s general functions in a wide range of biological contexts. SIRT6 plays an important role in gene silencing, metabolism, DNA repair, antioxidant defense, inflammation, aging and longevity, early development, and stress response. In addition, recent studies have revealed SIRT6’s role in macrophage polarization and mitochondrial homeostasis. Despite being initially understudied in the context of the eye, recent efforts have begun to elucidate the critical functions of SIRT6 in the retina and RPE. In the retina, SIRT6 is essential for adult retinal function, regulates energy metabolism by suppressing glycolysis that affects photoreceptor cell survival, protects retinal ganglion cells from oxidative stress, and plays a role in Müller cells during early neurodegenerative events in diabetic retinopathy. In the RPE, SIRT6 activates autophagy in culture and protects against oxidative stress in mice. Taken together, this review demonstrates that better understanding of SIRT6’s functions and their mechanisms, both in and out of the context of the eye, holds great promise for the development of SIRT6-targeted strategies for prevention and treatment of blinding eye diseases.

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Uvaol ameliorates lipid deposition in hyperlipidemic hepatocytes by suppressing protein-tyrosine phosphatase 1B/ER stress signaling

Gwon,

Chung,

Lim

et al. 2024

Biochemical and Biophysical Research Communications

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Human centenarian–associated SIRT6 mutants modulate hepatocyte metabolism and collagen deposition in multilineage hepatic 3D spheroids

Cited by 5 publications

References 77 publications

Nurturing longevity through natural compounds: Where do we stand, and where do we go?

Nurturing longevity through natural compounds: Where do we stand, and where do we go?

The many faces of SIRT6 in the retina and retinal pigment epithelium

Uvaol ameliorates lipid deposition in hyperlipidemic hepatocytes by suppressing protein-tyrosine phosphatase 1B/ER stress signaling

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