Rapamycin and Other Longevity-Promoting Compounds Enhance the Generation of Mouse Induced Pluripotent Stem Cells
Abstract
Summary: Reprogramming of somatic cells to a pluripotent state was first accomplished using retroviral vectors for transient expression of pluripotency‐associated transcription factors. This seminal work was followed by numerous studies reporting alternative (noninsertional) reprogramming methods and various conditions to improve the efficiency of reprogramming. These studies have contributed little to an understanding of global mechanisms underlying reprogramming efficiency. Here we report that inhibition of the mammalian target of rapamycin (mTOR) pathway by rapamycin or PP242 enhances the efficiency of reprogramming to induced pluripotent stem cells (iPSCs). Inhibition of the insulin/IGF‐1 signaling pathway, which like mTOR is involved in control of longevity, also enhances reprogramming efficiency. In addition, the small molecules used to inhibit these pathways also significantly improved longevity in Drosophila melanogaster. We further tested the potential effects of six other longevity‐promoting compounds on iPSC induction, including two sirtuin activators (resveratrol and fisetin), an autophagy inducer (spermidine), a PI3K (phosphoinositide 3‐kinase) inhibitor (LY294002), an antioxidant (curcumin), and an activating adenosine monophosphate‐activated protein kinase activator (metformin). With the exception of metformin, all of these chemicals promoted somatic cell reprogramming, though to different extents. Our results show that the controllers of somatic cell reprogramming and organismal lifespan share some common regulatory pathways, which suggests a new approach for studying aging and longevity based on the regulation of cellular reprogramming.
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Beside antioxidant activity, flavonoids have anti-inflammatory, vasodilator, anticoagulant, cardioprotective, anti-diabetic, neuroprotective, and anti-obesity activities, making them of interest as anti-aging compounds.
“Beside the antioxidant activity, flavonoids have anti-inflammatory, vasodilator, anticoagulant, cardioprotective, anti-diabetic, neuroprotective, and anti-obesity activities, which make them of great interest as anti-aging compounds (Table 3) [228,229,230,231,232,233,234,235,236,237,238,239,240,241,242,243,244,245,246,247,248,249,250,251,252,253,254,255,256,257].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [236]
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- Authors
- Chen, T., Shen, L., Yu, J., Wan, H., Guo, A., Chen, J., Long, Y., Zhao, J., & Pei, G.
- Affiliations
- Chinese Academy of Sciences (CN)
- National Center for Drug Screening (CN)
- Corresponding author
- Zhao, Jian
- Pei, Gang
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2011-06-14
- Volume
- 10
- Issue
- 5
- Pages
- 908-911
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- OpenAlex
- W1662658298
- Cited by
- 204
- References
- 26
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 8 · 2023: 8 · 2022: 15 · 2021: 12 · 2020: 15 · 2019: 7 · 2018: 21 · 2017: 7 · 2016: 14 · 2015: 19 · 2014: 26 · 2013: 23 · 2012: 21
- FWCI
- 9.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- induced pluripotent stem cells, somatic cell reprogramming, rapamycin, mTOR inhibition, PP242, insulin/IGF-1 signaling, longevity, lifespan extension, Drosophila melanogaster, sirtuin activators, resveratrol, fisetin, spermidine, autophagy, PI3K inhibition, LY294002, curcumin, metformin, AMPK, aging
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Aging, Animals, Chromones, Flavonoids, Longevity, Morpholines, Spermidine, Signal Transduction, Sirolimus, Flavonols, Mice, Induced Pluripotent Stem Cells, TOR Serine-Threonine Kinases, Cellular Reprogramming
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