Toxin-induced hormesis may restrain aging

Lajqi, Trim; Stojiljkovic, Milan; Wetzker, Reinhard

doi:10.1007/s10522-019-09806-5

Cited by 16 publications

(11 citation statements)

References 111 publications

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“…Low-dose effects such as hormesis (Sun et al 2020) as well as potential toxic effects at higher concentrations may remain unnoticed when using such a small range of concentrations. The hormesis effect is the biphasic response to low and high doses of chemical, biological, or physical exposures (Kendig et al 2010), and is responsible for the known beneficial effects of toxins or dangerous radiation in low doses (Feinendegen 2005;Lajqi et al 2019). However, several studies suggested that hormesis is also the main mechanism underlying the beneficial effects of natural extracts and polyphenols (Brunetti et al 2020;Di Rosa et al 2020;Martel et al 2019;Saul et al 2011;Sayed et al 2021).…”

Section: Weak Correspondence Of Pharyngeal Pumping Rate With Other Hementioning

confidence: 99%

Health and longevity studies in C. elegans: the “healthy worm database” reveals strengths, weaknesses and gaps of test compound-based studies

et al. 2021

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Several biogerontology databases exist that focus on genetic or gene expression data linked to health as well as survival, subsequent to compound treatments or genetic manipulations in animal models. However, none of these has yet collected experimental results of compound-related health changes. Since quality of life is often regarded as more valuable than length of life, we aim to fill this gap with the “Healthy Worm Database” (http://healthy-worm-database.eu). Literature describing health-related compound studies in the aging model Caenorhabditis elegans was screened, and data for 440 compounds collected. The database considers 189 publications describing 89 different phenotypes measured in 2995 different conditions. Besides enabling a targeted search for promising compounds for further investigations, this database also offers insights into the research field of studies on healthy aging based on a frequently used model organism. Some weaknesses of C. elegans-based aging studies, like underrepresented phenotypes, especially concerning cognitive functions, as well as the convenience-based use of young worms as the starting point for compound treatment or phenotype measurement are discussed. In conclusion, the database provides an anchor for the search for compounds affecting health, with a link to public databases, and it further highlights some potential shortcomings in current aging research.

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Section: Weak Correspondence Of Pharyngeal Pumping Rate With Other Hementioning

confidence: 99%

Health and longevity studies in C. elegans: the “healthy worm database” reveals strengths, weaknesses and gaps of test compound-based studies

et al. 2021

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“…Later on, several studies performed in macrophages and microglia revealed a pathogen dose-dependent development of trained immunity by priming with low doses of LPS or tolerance by high doses of LPS, after subsequent challenge with the same or a different stressor [5,[15][16][17]. The maturation state is yet another factor that may influence the induction of memory-like responses, and may explained the magnitude of priming [7,18,19]. Various seminal studies have shown that both memory-like inflammatory responses are accompanied by epigenetic reprogramming with resulting distinct changes in metabolism [8,[20][21][22].…”

Section: Introductionmentioning

confidence: 99%

LPS Induces Opposing Memory-like Inflammatory Responses in Mouse Bone Marrow Neutrophils

Lajqi

Braun

Kranig

et al. 2021

IJMS

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A growing body of evidence suggests that innate immune cells can respond in a memory-like (adaptive) fashion, which is referred to as trained immunity. Only few in vivo studies have shown training effects in neutrophils; however, no in vitro setup has been established to study the induction of trained immunity or tolerance in neutrophils by microbial agents. In light of their short lifespan (up to 48 h), we suggest to use the term trained sensitivity for neutrophils in an in vitro setting. Here, we firstly describe a feasible two-hit model, using different doses of lipopolysaccharide (LPS) in bone marrow neutrophils. We found that low doses (10 pg/mL) induce pro-inflammatory activation (trained sensitivity), whereas priming with high doses (100 ng/mL) leads to suppression of pro-inflammatory mediators such as TNF-α or IL-6 (tolerance) (p < 0.05). On a functional level, trained neutrophils displayed increased phagocytic activity and LFA-1 expression as well as migrational capacity and CD11a expression, whereas tolerant neutrophils show contrasting effects in vitro. Mechanistically, TLR4/MyD88/PI3Ks regulate the activation of p65, which controls memory-like responses in mouse bone marrow neutrophils (p < 0.05). Our results open a new window for further in vitro studies on memory-like inflammatory responses of short-lived innate immune cells such as neutrophils.

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“…Further studies displayed a pathogen dose-dependent induction of either innate memory by priming with low doses, or tolerance by high doses of sequential challenges with LPS, especially in macrophages and microglia ( 86 – 88 ). Moreover, cellular maturation is another important factor, influencing adaptive features through distinct signaling mechanisms ( 89 , 90 ). Activation of the phosphoinositide 3-kinase (PI3K)/mechanistic target of rapamycin (mTOR) pathway is critical for the induction of trained immunity in macrophages leading to an increased inflammatory response ( 91 ).…”

Section: Long-term Adaptation Of Neutrophilsmentioning

confidence: 99%

“…It is well-known that the pro-inflammatory activity of various innate immune cells increases whilst aging ( 89 , 129 , 130 ). The pro-inflammatory activity of neutrophils characterized by increased tissue infiltration, phagocytosis and NET formation expands with age and is regulated particularly by the TLR4/MyD88 pathway ( 131 ).…”

Section: Long-term Adaptation Of Neutrophilsmentioning

confidence: 99%

The Role of Microbiota in Neutrophil Regulation and Adaptation in Newborns

et al. 2020

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Newborns are highly susceptible to infections and mainly rely on innate immune functions. Reduced reactivity, delayed activation and subsequent failure to resolve inflammation however makes the neonatal immune system a very volatile line of defense. Perinatal microbiota, nutrition and different extra-uterine factors are critical elements that define long-term outcomes and shape the immune system during the neonatal period. Neutrophils are first responders and represent a vital component of the immune system in newborns. They have long been regarded as merely executive immune cells, however this notion is beginning to shift. Neutrophils are shaped by their surrounding and adaptive elements have been described. The role of “innate immune memory” and the main triangle connection microbiome—neutrophil—adaptation will be discussed in this review.

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Toxin-induced hormesis may restrain aging

Cited by 16 publications

References 111 publications

Health and longevity studies in C. elegans: the “healthy worm database” reveals strengths, weaknesses and gaps of test compound-based studies

Health and longevity studies in C. elegans: the “healthy worm database” reveals strengths, weaknesses and gaps of test compound-based studies

LPS Induces Opposing Memory-like Inflammatory Responses in Mouse Bone Marrow Neutrophils

The Role of Microbiota in Neutrophil Regulation and Adaptation in Newborns

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