FPR1 is essential for rapamycin-induced lifespan extension in Saccharomyces cerevisiae

Yalcin, Gulperi; Kim, Juri; Seo, Dongseong; Lee, Cheol Koo

doi:10.1016/j.bbrc.2023.02.063

Cited by 3 publications

(2 citation statements)

References 35 publications

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“…The role of mTOR in aging has been consistently shown throughout evolution as a conserved signaling molecule that integrates diverse environmental and intracellular signals. This has led to the establishment of a growing body of evidence regarding the efficacy of rapamycin in increasing lifespan and/or healthspan in the most diverse experimental models, from yeast [38] to monkeys [39]. The effect of rapamycin on immunosenescence is currently under investigation in preclinical [40] and clinical settings [41].…”

Section: Discussionmentioning

confidence: 99%

Senotherapeutic Peptide 14 Suppresses Th1 and M1 Human T Cell and Monocyte Subsets In Vitro

Alencar-Silva,

Barcelos,

Silva-Carvalho

et al. 2024

Cells

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Inflammation contributes to the onset and exacerbation of numerous age-related diseases, often manifesting as a chronic condition during aging. Given that cellular senescence fosters local and systemic inflammation, senotherapeutic interventions could potentially aid in managing or even reducing inflammation. Here, we investigated the immunomodulatory effects of the senotherapeutic Peptide 14 (Pep 14) in human peripheral blood mononuclear cells (PBMCs), monocytes, and macrophages. We found that, despite failing to significantly influence T cell activation and proliferation, the peptide promoted a Th2/Treg gene expression and cytokine signature in PBMCs, characterized by increased expression of the transcription factors GATA3 and FOXP3, as well as the cytokines IL-4 and IL-10. These observations were partially confirmed through ELISA, in which we observed increased IL-10 release by resting and PHA-stimulated PBMCs. In monocytes from the U-937 cell line, Pep 14 induced apoptosis in lipopolysaccharide (LPS)-stimulated cells and upregulated IL-10 expression. Furthermore, Pep 14 prevented LPS-induced activation and promoted an M2-like polarization in U-937-derived macrophages, evidenced by decreased expression of M1 markers and increased expression of M2 markers. We also showed that the conditioned media from Pep 14-treated macrophages enhanced fibroblast migration, indicative of a functional M2 phenotype. Taken together, our findings suggest that Pep 14 modulates immune cell function towards an anti-inflammatory and regenerative phenotype, highlighting its potential as a therapeutic intervention to alleviate immunosenescence-associated dysregulation.

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Section: Discussionmentioning

confidence: 99%

Senotherapeutic Peptide 14 Suppresses Th1 and M1 Human T Cell and Monocyte Subsets In Vitro

Alencar-Silva,

Barcelos,

Silva-Carvalho

et al. 2024

Cells

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“…Rapamycin binds to the yeast proline rotamase 1 protein Fpr1, a homolog of the mammalian prolyl isomerase FK506‐binding protein FKBP12, inhibits TORC1 activity, and extends CLS in S. cerevisiae in an autophagy‐dependent manner. [ 30–33 ] In S. pombe , rapamycin does not affect cell growth but does extends CLS. [ 34,35 ] Lifespan extension via rapamycin‐induced TORC1 inhibition has also been observed in model organisms such as nematodes, flies, and mice.…”

Section: Low‐molecular Weight Compounds That Extend the Chronological...mentioning

confidence: 99%

Low‐Molecular Weight Compounds that Extend the Chronological Lifespan of Yeasts, Saccharomyces cerevisiae, and Schizosaccharomyces pombe

Ohtsuka,

Shimasaki,

Aiba

2024

Advanced Biology

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Yeast is an excellent model organism for research for regulating aging and lifespan, and the studies have made many contributions to date, including identifying various factors and signaling pathways related to aging and lifespan. More than 20 years have passed since molecular biological perspectives are adopted in this research field, and intracellular factors and signal pathways that control aging and lifespan have evolutionarily conserved from yeast to mammals. Furthermore, these findings have been applied to control the aging and lifespan of various model organisms by adjustment of the nutritional environment, genetic manipulation, and drug treatment using low‐molecular weight compounds. Among these, drug treatment is easier than the other methods, and research into drugs that regulate aging and lifespan is consequently expected to become more active. Chronological lifespan, a definition of yeast lifespan, refers to the survival period of a cell population under nondividing conditions. Herein, low‐molecular weight compounds are summarized that extend the chronological lifespan of Saccharomyces cerevisiae and Schizosaccharomyces pombe, along with their intracellular functions. The low‐molecular weight compounds are also discussed that extend the lifespan of other model organisms. Compounds that have so far only been studied in yeast may soon extend lifespan in other organisms.

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TOR2 plays the central role in rapamycin-induced lifespan extension in budding yeast

Seo,

Yalcin,

Jang

et al. 2024

Biochemical and Biophysical Research Communications

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FPR1 is essential for rapamycin-induced lifespan extension in Saccharomyces cerevisiae

Cited by 3 publications

References 35 publications

Senotherapeutic Peptide 14 Suppresses Th1 and M1 Human T Cell and Monocyte Subsets In Vitro

Senotherapeutic Peptide 14 Suppresses Th1 and M1 Human T Cell and Monocyte Subsets In Vitro

Low‐Molecular Weight Compounds that Extend the Chronological Lifespan of Yeasts, Saccharomyces cerevisiae, and Schizosaccharomyces pombe

TOR2 plays the central role in rapamycin-induced lifespan extension in budding yeast

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