Recent progresses on anti-aging compounds and their targets in Caenorhabditis elegans

Kim, Eun Ji E.; Lee, Seung-Jae

doi:10.1016/j.tma.2019.11.003

Cited by 10 publications

(6 citation statements)

References 22 publications

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“…In previous work, more than 100'000 compounds have been screened, and about 100 compounds have been identified to increase C. elegans lifespan (Supplementary Table 5) (Kim et al, 2019;Lucanic et al, 2013;Petrascheck et al, 2007;Ye et al, 2014). A practical limitation in verifying drug candidates is the unknown dosage to be used.…”

Section: Discussionmentioning

confidence: 99%

Youthful and age-related matreotypes predict drugs promoting longevity

Statzer

Jongsma

Liu

et al. 2021

Preprint

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The identification and validation of drugs that promote health during aging (‘geroprotectors’) is key to the retardation or prevention of chronic age-related diseases. Here we found that most of the established pro-longevity compounds shown to extend lifespan in model organisms also alter extracellular matrix gene expression (i.e., matrisome) in human cell lines. To harness this novel observation, we used age-stratified human transcriptomes to define the age-related matreotype, which represents the matrisome gene expression pattern associated with age. Using a ‘youthful’ matreotype, we screened in silico for geroprotective drug candidates. To validate drug candidates, we developed a novel tool using prolonged collagen expression as a non-invasive and in-vivo surrogate marker for C. elegans longevity. With this reporter, we were able to eliminate false positive drug candidates and determine the appropriate dose for extending the lifespan of C. elegans. We improved drug uptake for one of our predicted compounds, genistein, and reconciled previous contradictory reports of its effects on longevity. We identified and validated new compounds, tretinoin, chondroitin sulfate, and hyaluronic acid, for their ability to restore age-related decline of collagen homeostasis and increase lifespan. Thus, our innovative drug screening approach - employing extracellular matrix homeostasis - facilitates the discovery of pharmacological interventions promoting healthy aging.HighlightsMany geroprotective drugs alter extracellular matrix gene expressionDefined young and old human matreotype signatures can identify novel potential geroprotective compoundsProlonged collagen homeostasis as a surrogate marker for longevity

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Section: Discussionmentioning

confidence: 99%

Youthful and age-related matreotypes predict drugs promoting longevity

Statzer

Jongsma

Liu

et al. 2021

Preprint

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“…C. elegans is a suitable model organism for aging related experimentation because of its short lifespan, simple physiology, and genetic tractability [ 12 ]. Additionally, several fundamental genetic pathways that regulate aging process in C. elegans are conserved in mammals [ 12 ]. Here, we studied the lifespan-extending mechanism of FA in C. elegans .…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, antioxidant supplementation is supposed to be an effective strategy to delay aging [11]. C. elegans is a suitable model organism for aging related experimentation because of its short lifespan, simple physiology, and genetic tractability [12]. Additionally, several fundamental genetic pathways that regulate aging process in C. elegans are conserved in mammals [12].…”

Section: Introductionmentioning

confidence: 99%

Ferulic Acid Supplementation Increases Lifespan and Stress Resistance via Insulin/IGF-1 Signaling Pathway in C. elegans

Meng

et al. 2021

IJMS

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Ferulic acid (FA) is a naturally-occurring well-known potent antioxidant and free radical scavenger. FA supplementation is an effective strategy to delay aging, but the underlying mechanism remains unknown. In the present study, we examined the effects of FA on lifespan extension and its mechanism of FA in Caenorhabditis elegans (C. elegans). Results suggested that FA increased the lifespan of C. elegans, rather than altering the growth of E. coli OP50. Meanwhile, FA promoted the healthspan of C. elegans by improving locomotion and reducing fat accumulation and polyQ aggregation. FA increased the resistance to heat and oxidative stress through reducing ROS. The upregulating of the expression of the hlh-30, skn-1, and hsf-1 were involved in the FA-mediated lifespan extension. Furthermore, FA treatment had no impact on the lifespan of daf-2, hlh-30, skn-1, and hsf-1 mutants, confirming that insulin/IGF-1 signaling pathway and multiple longevity mechanisms were associated with the longevity mechanism of FA. We further found that mitochondrial signaling pathway was modulation involved in FA-mediated lifespan extension. With the results from RNA-seq results and mutants lifespan assay. These findings contribute to our knowledge of the lifespan extension and underlying mechanism of action of FA in C. elegans.

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“…One of the largest screens assessed 1,300 compounds on about 20,000 mice performing full lifespans and yielded five longevity-promoting compounds (WO2018075641A1 and US 20200254006 A1). Using C. elegans, more than 100,000 compounds have been screened collectively across multiple studies, and about 100 compounds have been identified that increase C. elegans lifespan ( Petrascheck et al, 2007 ; Lucanic et al, 2013 ; Ye et al, 2014 ; Kim and Lee, 2019 ; Statzer et al, 2021 ). Pathway analysis of these discovered longevity compounds showed enrichment for TGFβ pathway, chondroitin, and heparan sulfate biogenesis as potential drug-protein targets ( Liu et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Drug Screening Implicates Chondroitin Sulfate as a Potential Longevity Pill

Ewald

2021

Front. Aging

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Discovering compounds that promote health during aging (“geroprotectors”) is key to the retardation of age-related pathologies and the prevention of chronic age-related diseases. In in-silico and model organisms’ lifespan screens, chondroitin sulfate has emerged as a geroprotective compound. Chondroitin sulfate is a glycosaminoglycan attached to extracellular matrix proteins and is naturally produced by our body. Oral supplementation of chondroitin sulfate shows a high tolerance in humans, preferable pharmacokinetics, a positive correlation with healthy human longevity, and efficacy in deceleration of age-related diseases in randomized clinical trials. We have recently shown that chondroitin sulfate supplementation increases the lifespan of C. elegans. Thus, chondroitin sulfate holds the potential to become a geroprotective strategy to promote health during human aging. This review discusses the two major potential mechanisms of action, extracellular matrix homeostasis and inhibition of inflammation, that counteract age-related pathologies upon chondroitin sulfate supplementation.

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Recent progresses on anti-aging compounds and their targets in Caenorhabditis elegans

Cited by 10 publications

References 22 publications

Youthful and age-related matreotypes predict drugs promoting longevity

Youthful and age-related matreotypes predict drugs promoting longevity

Ferulic Acid Supplementation Increases Lifespan and Stress Resistance via Insulin/IGF-1 Signaling Pathway in C. elegans

Drug Screening Implicates Chondroitin Sulfate as a Potential Longevity Pill

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