Inflammaging is driven by upregulation of innate immune receptors and systemic interferon signaling and is ameliorated by dietary restriction

Rasa, Seyed Mohammad Mahdi; Annunziata, Francesco; Křepelová, Anna; Nunna, Suneetha; Omrani, Omid; Gebert, Nadja; Adam, Lisa; Käppel, Sandra; Höhn, Sven; Donati, Giacomo; Jurkowski, Tomasz P.; Rudolph, K. Lenhard; Ori, Alessandro; Neri, Francesco

doi:10.1016/j.celrep.2022.111017

Cited by 26 publications

(20 citation statements)

References 67 publications

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“…RS may alleviate inflammaging directly, or indirectly by removing the damage signals that cause it. Senolysis eliminates senescent cells thereby reducing SASP (senescence-associated secretory phenotype) that involves many inflammatory signals 44 ; Rasa et al suggested CR curbs inflammation by reducing chromatin accessibility of an inflammation-associated genetic network 4 . IVPR has been shown to have a rejuvenative effect both ex vivo 45 and in vivo 46 , which could involve deactivating stress signals from damaged cells.…”

Section: Discussionmentioning

confidence: 99%

“…A central question is what, if any, are the shared effects and mechanisms of action for these disparate interventions. Recently, extensive transcriptomic data pertaining to the four major rejuvenation strategies (RS) became available [3][4][5][6] , calling for a comprehensive comparative analysis. Directly comparing the gene expression signatures of RS to one another and to that of normal aging may illuminate core aspects of rejuvenation and uncover new targets for therapeutics.…”

Section: Introductionmentioning

confidence: 99%

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Rejuvenation strategies share gene expression programs of reduced inflammation and downstream restored fatty acid metabolism

Landsberger

Amit

Alon

2022

Preprint

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Mammalian aging is accompanied by low-grade chronic inflammation (CI), termed inflammaging, commonly regarded as a proximal cause of aging-related dysfunction. Inflammaging is thought to lie downstream of core drivers of aging consisting of cellular and molecular changes and damage forms, such as aberrant epigenomes and transcriptomes. Here we test the reverse hypothesis, that CI itself causes multiple aging-related changes at the transcriptional level - and thus that inflammation is a core driver of aging and some of the transcriptional changes are downstream of it. By analyzing bulk and single-cell RNA sequencing data, we find that interventions in lung, liver, and kidney that cause CI in young mice partially recapitulate the gene expression signature of aging mice in the same organs. This recapitulation occurs in most measured cell populations, including parenchymal, immune and stromal cells, and consists of both inflammation signals themselves and non-inflammation related genes. We find that senolytic treatment reverses the shared gene expression component of aging and CI. The results point to the potential role of age-dependent CI as a core driver of aging.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rejuvenation strategies share gene expression programs of reduced inflammation and downstream restored fatty acid metabolism

Landsberger

Amit

Alon

2022

Preprint

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“…For instance, age significantly modifies the landscape of the immune system. These ageing changes are well documented in age-related pathologies such as Alzheimer's, arthritis, hypertension and atherosclerosis, which is linked to chronic inflammation and interferon activation [16]- [18]. Additionally, preexisting cross-reactive T-cells, such as in the CD4+ memory compartment being required for a robust vaccine response to HBV [19].…”

Section: Introductionmentioning

confidence: 99%

Multi-view learning to unravel the different levels underlying hepatitis B vaccine response

Affaticati

Bartholomeus

Mullan

et al. 2023

Preprint

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Background: The high complexity of biological systems arises from the large number of spatially and functionally overlapping interconnected components constituting them. The immune system, which is built of reticular components working to ensure host survival from microbial threats, presents itself as particularly intricate. A vaccine response is likely governed by levels that, when considered separately, may only partially explain the mechanisms at play. Multi-view modelling can aid in gaining actionable insights on response markers shared across populations, capture the immune system diversity, and disentangle confounders. Hepatitis B virus (HBV) vaccination responsiveness acts as a feasibility study for such an approach. Material and methods: Seroconversion to vaccine induced antibodies against HBV surface antigen (anti-HBs) in a vaccination cohort containing early-converters (n=21 ; <2 month) and late-converters (n=9 ; <6 months), was based on the anti-HBs titres (>10IU/L). Two approaches (principal component analysis and canonical correlation analysis) were used to interpret the multi-view data which encompassed bulk RNAseq, CD4+ T cell parameters (including T-cell receptor data), flow cytometry data, metadata including gender and age of the baseline parameters. Results: Multi-view joint dimensionality reduction out-performed single-view methods in terms of AUC and balanced accuracy, confirming an increase in predictive power to be gained. The interpretation of the findings showed that age, gender, inflammation-related genesets and pre-existing vaccine specific T-cells were associated with vaccination responsiveness. Conclusion: This multi-view dimensionality reduction approach complements the clinical seroconversion and all single-modalities and could identify what features underpin HBV vaccine response. This methodology could be extended to other vaccination trials to identify key features regulating responsiveness.

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“…Over time, the accumulation of senescent cells contributes to an increasing list of pathologies in tissues and accelerates the aging of tissues and organs [ 7 ]. There are many causes inducing cellular senescence, including oxidative stress, DNA damage, telomere shortening [ 11 , 12 ], and inflammation [ 13 ]. Homeostasis of senescent cells changes markedly, disrupting mitochondrial electron transport chain, resulting in the leakage of ROS [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…Excessive ROS can impair mitochondria and nuclear DNA, resulting in a positive feedback loop to reinforce cell cycle arrest [ 10 ]. In addition, ROS also accelerate the rate of telomere shortening [ 14 ], promote inflammation and apoptosis [ 13 ], and accelerate aging.…”

Section: Introductionmentioning

confidence: 99%

Nobiletin Prevents D-Galactose-Induced C2C12 Cell Aging by Improving Mitochondrial Function

Sun

Sang

et al. 2022

IJMS

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Age-associated loss of skeletal muscle mass and function is one of the main causes of the loss of independence and physical incapacitation in the geriatric population. This study used the D-galactose-induced C2C12 myoblast aging model to explore whether nobiletin (Nob) could delay skeletal muscle aging and determine the associated mechanism. The results showed that Nob intervention improved mitochondrial function, increased ATP production, reduced reactive oxygen species (ROS) production, inhibited inflammation, and prevented apoptosis as well as aging. In addition, Nob improved autophagy function, removed misfolded proteins and damaged organelles, cleared ROS, reduced mitochondrial damage, and improved skeletal muscle atrophy. Moreover, our results illustrated that Nob can not only enhance mitochondrial function, but can also enhance autophagy function and the protein synthesis pathway to inhibit skeletal muscle atrophy. Therefore, Nob may be a potential candidate for the prevention and treatment of age-related muscle decline.

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Inflammaging is driven by upregulation of innate immune receptors and systemic interferon signaling and is ameliorated by dietary restriction

Cited by 26 publications

References 67 publications

Rejuvenation strategies share gene expression programs of reduced inflammation and downstream restored fatty acid metabolism

Rejuvenation strategies share gene expression programs of reduced inflammation and downstream restored fatty acid metabolism

Multi-view learning to unravel the different levels underlying hepatitis B vaccine response

Nobiletin Prevents D-Galactose-Induced C2C12 Cell Aging by Improving Mitochondrial Function

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