A new AMPK isoform mediates glucose-restriction induced longevity non-cell autonomously by promoting membrane fluidity

Jeong, Jin-Hyuck; Han, Jun-Seok; Jung, Yeonji; Lee, Seung-Min; Park, So‐Hyun; Park, Mooncheol; Shin, Min-Gi; Kim, Nami; Kang, Mi Sun; Kim, Seokho; Lee, Kwang-Pyo; Kwon, Ki‐Sun; Kim, Chun-A.; Yang, Yong Ryoul; Hwang, Geum‐Sook; Kwon, Eun-Soo

doi:10.1038/s41467-023-35952-z

Cited by 19 publications

(20 citation statements)

References 114 publications

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“…The authors treated the cells with different doses of different MDPs to quantify autophagosomes and autolysosomes. They treated the cells with HNG, a potent analog of humanin, which has cytoprotective roles in various age-related diseases [ 116 , 118 , 119 ], proposed as a dietary restriction mimetic peptide by activating AMPK [ 120 ].…”

Section: Resultsmentioning

confidence: 99%

Humanin and Its Pathophysiological Roles in Aging: A Systematic Review

Coradduzza

Congiargiu

Chen

et al. 2023

Biology

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Background: Senescence is a cellular aging process in all multicellular organisms. It is characterized by a decline in cellular functions and proliferation, resulting in increased cellular damage and death. These conditions play an essential role in aging and significantly contribute to the development of age-related complications. Humanin is a mitochondrial-derived peptide (MDP), encoded by mitochondrial DNA, playing a cytoprotective role to preserve mitochondrial function and cell viability under stressful and senescence conditions. For these reasons, humanin can be exploited in strategies aiming to counteract several processes involved in aging, including cardiovascular disease, neurodegeneration, and cancer. Relevance of these conditions to aging and disease: Senescence appears to be involved in the decay in organ and tissue function, it has also been related to the development of age-related diseases, such as cardiovascular conditions, cancer, and diabetes. In particular, senescent cells produce inflammatory cytokines and other pro-inflammatory molecules that can participate to the development of such diseases. Humanin, on the other hand, seems to contrast the development of such conditions, and it is also known to play a role in these diseases by promoting the death of damaged or malfunctioning cells and contributing to the inflammation often associated with them. Both senescence and humanin-related mechanisms are complex processes that have not been fully clarified yet. Further research is needed to thoroughly understand the role of such processes in aging and disease and identify potential interventions to target them in order to prevent or treat age-related conditions. Objectives: This systematic review aims to assess the potential mechanisms underlying the link connecting senescence, humanin, aging, and disease.

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Section: Resultsmentioning

confidence: 99%

Humanin and Its Pathophysiological Roles in Aging: A Systematic Review

Coradduzza

Congiargiu

Chen

et al. 2023

Biology

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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%

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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“…(b) A glucose-restricted diet activates a neuronal AMPK variant, resulting in neuropeptide release and activation of NHR-49. NHR-49 function requires PAQR-2 activity in a glucose-restricted dietary regimen to induce membrane fluidity via ∆9 desaturases [69]. Red-colored phospholipids indicate phospholipids with double bonds in their acyl chains.…”

Section: Sensing Membrane Rigidification Is Essential For Membrane Fl...mentioning

confidence: 99%

“…Under such a dietary condition, PAQR-2 is required to readjust membrane fluidity to alleviate the membrane rigidifying and toxic effect of glucose. Conversely, a glucose-restricted diet based on an E. coli glucosedepleted mutant improves C. elegans healthspan by promoting membrane fluidity [69]. The beneficial effect of a glucose-restricted diet is mediated by a neuronal version of the AMP-activated protein kinase (AMPK) and requires PAQR-2 and its downstream effector NHR-49 (Figure 1b).…”

Section: Mammalian Adiponectin Receptors Signal To Downstream Lipid R...mentioning

confidence: 99%

Molecular Mechanisms of Lipid-Based Metabolic Adaptation Strategies in Response to Cold

Baumeister

2023

Cells

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Temperature changes and periods of detrimental cold occur frequently for many organisms in their natural habitats. Homeothermic animals have evolved metabolic adaptation strategies to increase mitochondrial-based energy expenditure and heat production, largely relying on fat as a fuel source. Alternatively, certain species are able to repress their metabolism during cold periods and enter a state of decreased physiological activity known as torpor. By contrast, poikilotherms, which are unable to maintain their internal temperature, predominantly increase membrane fluidity to diminish cold-related damage from low-temperature stress. However, alterations of molecular pathways and the regulation of lipid-metabolic reprogramming during cold exposure are poorly understood. Here, we review organismal responses that adjust fat metabolism during detrimental cold stress. Cold-related changes in membranes are detected by membrane-bound sensors, which signal to downstream transcriptional effectors, including nuclear hormone receptors of the PPAR (peroxisome proliferator-activated receptor) subfamily. PPARs control lipid metabolic processes, such as fatty acid desaturation, lipid catabolism and mitochondrial-based thermogenesis. Elucidating the underlying molecular mechanisms of cold adaptation may improve beneficial therapeutic cold treatments and could have important implications for medical applications of hypothermia in humans. This includes treatment strategies for hemorrhagic shock, stroke, obesity and cancer.

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A new AMPK isoform mediates glucose-restriction induced longevity non-cell autonomously by promoting membrane fluidity

Cited by 19 publications

References 114 publications

Humanin and Its Pathophysiological Roles in Aging: A Systematic Review

Humanin and Its Pathophysiological Roles in Aging: A Systematic Review

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

Molecular Mechanisms of Lipid-Based Metabolic Adaptation Strategies in Response to Cold

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