Healthspan Pharmacology

Jafari, Mahvash

doi:10.1089/rej.2015.1774

“…Though life span is a key parameter of aging, it is not the only one. Health span represents an equally, if not more, important measure in normal aging (27). As animals age, their ability to survive environmental insults deceases.…”

Section: Loss Of the Gaba B Receptor Gene Gbb-1 And Gabamentioning

confidence: 99%

GABA receptors differentially regulate life span and health span in C. elegans through distinct downstream mechanisms

Yuan

¹

,

Zhou

²

,

Xu

³

et al. 2019

American Journal of Physiology-Cell Physiology

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GABA, a prominent inhibitory neurotransmitter, is best known to regulate neuronal functions in the nervous system. However, much less is known about the role of GABA signaling in other physiological processes. Interestingly, recent work showed that GABA signaling can regulate life span via a metabotropic GABAB receptor in Caenorhabditis elegans. However, the role of other types of GABA receptors in life span has not been clearly defined. It is also unclear whether GABA signaling regulates health span. Here, using C. elegans as a model, we systematically interrogated the role of various GABA receptors in both life span and health span. We find that mutations in four different GABA receptors extend health span by promoting resistance to stress and pathogen infection and that two such receptor mutants also show extended life span. Different GABA receptors engage distinct transcriptional factors to regulate life span and health span, and even the same receptor regulates life span and health span via different transcription factors. Our results uncover a novel, profound role of GABA signaling in aging in C. elegans, which is mediated by different GABA receptors coupled to distinct downstream effectors.

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“…80 This provides the ability to study phenotypes that are challenging to assess in most vertebrate animal models, such as healthspan (the part of an organism's lifespan during which it is healthy). 82,83 Invertebrate models can also be T A B L E 2 Highlights of good practices for the translational relevance of in vitro models assessing NP bioactivities and mechanisms of action 1. Artefacts.…”

Section: Invertebrate In Vivo Modelsmentioning

confidence: 99%

“…The conservation of many human genes and signaling networks, combined with the small size and relatively short lifespans of these models, facilitates the cost‐effective evaluation of a variety of phenotypes (eg, reproduction, locomotion, cognition) in a large number of individuals (Table ) . This provides the ability to study phenotypes that are challenging to assess in most vertebrate animal models, such as healthspan (the part of an organism’s lifespan during which it is healthy) . Invertebrate models can also be used in more focused interventional and mechanistic studies that explore specific aspects of an established phenotype .…”

Section: Good Practices For Preclinical Np Studiesmentioning

confidence: 99%

“…80 This provides the ability to study phenotypes that are challenging to assess in most vertebrate animal models, such as healthspan (the part of an organism's lifespan during which it is healthy). 82,83 Invertebrate models can also be used in more focused interventional and mechanistic studies that explore specific aspects of an established phenotype. [84][85][86] For example, tea polyphenols were reported to modulate both stress responses and fertility in D. melanogaster strains 87 via a non-target-ligand mechanism of action (Table 2), by modulating iron homeostasis.…”

Section: Invertebrate In Vivo Modelsmentioning

confidence: 99%

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Improving natural product research translation: From source to clinical trial

Sorkin

¹

,

Kuszak

²

,

Bloss

³

et al. 2019

Self Cite

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While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a Septe mber, 2018 trans disci plina ry workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research. K E Y W O R D S clinical predictive validity, dietary supplements, model systems, rigor and replicability, value of information | 43 SORKIN et al.still provide invaluable guidance, the results of such trials are often met with concerns that different design choiceswhether of product, dose, timing, participant eligibility criteria, outcomes, etc.-might have yielded a substantially different result. Each interventional trial represents a substantial investment, with well-powered Phase III CTs typically consuming more than $10 million and many person-years. 9,10 Additionally, as time and funds are limited, and participant pools may also be constrained, a decision to invest in a CT often precludes pursuing other research questions, 11 which may provide more useful public health-relevant knowledge than an RCT with an insufficient evidence base.

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“…The conservation of many human genes and signaling networks, combined with the small size and relatively short lifespans of these models facilitate the cost-effective evaluation of a variety of phenotypes (e.g., reproduction, locomotion, cognition) in a large number of individuals ( Table 4) (79). This provides the ability to study phenotypes that are challenging to assess in most vertebrate animal models, such as healthspan (the part of an organism's lifespan during which it is healthy) (81,82). Invertebrate models can also be used in more focused interventional and mechanistic studies that explore specific aspects of an established phenotype (83)(84)(85).…”

Section: Invertebrate In Vivo Modelsmentioning

confidence: 99%

Improving Natural Product Research Translation: from Source to Clinical Trial

Sorkin¹,

Kuszak²,

Fukagawa³

et al. 2019

Preprint

Self Cite

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While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a https://events-support.com/events/Natural_Product_Clinical_Trials. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research.

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Healthspan Pharmacology

Cited by 10 publications

References 105 publications

GABA receptors differentially regulate life span and health span in C. elegans through distinct downstream mechanisms

GABA receptors differentially regulate life span and health span in C. elegans through distinct downstream mechanisms

Improving natural product research translation: From source to clinical trial

Improving Natural Product Research Translation: from Source to Clinical Trial

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