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Review

Molecular and Cellular Microbiology (MCM)  |  Bioactive Compounds and Functional Foods

Impacts of Senolytic Phytochemicals on Gut Microbiota: A Comprehensive Review

Hee Soo Kim1,2 and Chang Hwa Jung1,2*

1Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
2Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do 55365, Republic of Korea

Correspondence to:
Chang Hwa Jung,       chjung@kfri.re.kr
Received: August 19, 2024; Revised: October 21, 2024; Accepted: October 29, 2024

J. Microbiol. Biotechnol. 2024; 34(11): 2166-2172

Published November 28, 2024 https://doi.org/10.4014/jmb.2408.08032

Copyright © The Korean Society for Microbiology and Biotechnology.

Abstract

There is increasing interest in utilizing senolytics to selectively remove senescent cells from intestinal tissues, with the aim of maintaining a healthy gut environment during aging. This strategy underscores the potential of senolytics to enhance gut health by delaying intestinal aging and positively modulating gut microbiota. Certain plant-based phytochemicals have demonstrated promising senolytic effects. Beyond their ability to eliminate senescent cells, these compounds also exhibit antioxidant and anti-inflammatory properties, reducing oxidative stress and inflammation-key drivers of age-related diseases. By selectively removing senescent cells from the intestine, senolytic phytochemicals contribute to an improved intestinal inflammatory environment and promote the growth of a diverse microbial community. Ultimately, the dietary intake of these senolytic phytochemicals aids in maintaining a healthier intestinal microenvironment by targeting and clearing aged enterocytes.

Keywords

Senolytic, senescence, aging, gut, phytochemical

Graphical Abstract


References

  1. Lopes-Paciencia S, Saint-Germain E, Rowell MC, Ruiz AF, Kalegari P, Ferbeyre G. 2019. The senescence-associated secretory phenotype and its regulation. Cytokine 117: 15-22.
    Pubmed
  2. Lujambio A, Akkari L, Simon J, Grace D, Tschaharganeh DF, Bolden JE, et al. 2013. Non-cell-autonomous tumor suppression by p53. Cell 153: 449-460.
    Pubmed PMC
  3. Gasek NS, Kuchel GA, Kirkland JL, Xu M. 2021. Strategies for targeting senescent cells in human disease. Nat. Aging 1: 870-879.
    Pubmed PMC
  4. Chandeck C, Mooi WJ. 2010. Oncogene-induced cellular senescence. Adv. Anat. Pathol. 17: 42-48.
    Pubmed
  5. Nousis L, Kanavaros P, Barbouti A. 2023. Oxidative stress-induced cellular senescence: is labile iron the connecting link? Antioxidants (Basel) 12: 1250.
    Pubmed PMC
  6. Miwa S, Kashyap S, Chini E, von Zglinicki T. 2022. Mitochondrial dysfunction in cell senescence and aging. J. Clin. Invest. 132:e158774.
    Pubmed PMC
  7. Peng X, Wu Y, Brouwer U, van Vliet T, Wang B, Demaria M, et al. 2020. Cellular senescence contributes to radiation-induced hyposalivation by affecting the stem/progenitor cell niche. Cell Death Dis. 11: 854.
    Pubmed PMC
  8. Guillon J, Petit C, Toutain B, Guette C, Lelievre E, Coqueret O. 2019. Chemotherapy-induced senescence, an adaptive mechanism driving resistance and tumor heterogeneity. Cell Cycle 18: 2385-2397.
    Pubmed PMC
  9. Soto-Gamez A, Quax WJ, Demaria M. 2019. Regulation of survival networks in senescent cells: From mechanisms to interventions. J. Mol. Biol. 431: 2629-2643.
    Pubmed
  10. Hickson LJ, Langhi Prata LGP, Bobart SA, Evans TK, Giorgadze N, Hashmi SK, et al. 2019. Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine 47: 446-456.
    Pubmed PMC
  11. Chen J. 2016. The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harb. Perspect. Med. 6: a026104.
    Pubmed PMC
  12. Seluanov A, Gorbunova V, Falcovitz A, Sigal A, Milyavsky M, Zurer I, et al. 2001. Change of the death pathway in senescent human fibroblasts in response to DNA damage is caused by an inability to stabilize p53. Mol. Cell Biol. 21: 1552-1564.
    Pubmed PMC
  13. Zhu Y, Tchkonia T, Pirtskhalava T, Gower AC, Ding H, Giorgadze N, et al. 2015. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14: 644-658.
    Pubmed PMC
  14. Fuhrmann-Stroissnigg H, Ling YY, Zhao J, McGowan SJ, Zhu Y, Brooks RW, et al. 2017. Identification of HSP90 inhibitors as a novel class of senolytics. Nat. Commun. 8: 422.
    Pubmed PMC
  15. Zhu Y, Tchkonia T, Fuhrmann-Stroissnigg H, Dai HM, Ling YY, Stout MB, et al. 2016. Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell 15: 428-435.
    Pubmed PMC
  16. Zhu Y, Doornebal EJ, Pirtskhalava T, Giorgadze N, Wentworth M, Fuhrmann-Stroissnigg H, et al. 2017. New agents that target senescent cells: the flavone, fisetin, and the BCL-X(L) inhibitors, A1331852 and A1155463. Aging (Albany NY) 9: 955-963.
    Pubmed PMC
  17. Huang B, Vassilev LT. 2009. Reduced transcriptional activity in the p53 pathway of senescent cells revealed by the MDM2 antagonist nutlin-3. Aging (Albany NY) 1: 845-854.
    Pubmed PMC
  18. Baar MP, Brandt RMC, Putavet DA, Klein JDD, Derks KWJ, Bourgeois BRM, et al. 2017. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell 169: 132-147 e116.
    Pubmed PMC
  19. Nogueira V, Park Y, Chen CC, Xu PZ, Chen ML, Tonic I, et al. 2008. Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosis. Cancer Cell 14: 458-470.
    Pubmed PMC
  20. Schlessinger J. 2000. New roles for Src kinases in control of cell survival and angiogenesis. Cell 100: 293-296.
    Pubmed
  21. Anerillas C, Herman AB, Rossi M, Munk R, Lehrmann E, Martindale JL, et al. 2022. Early SRC activation skews cell fate from apoptosis to senescence. Sci. Adv. 8: eabm0756.
    Pubmed PMC
  22. Rivera-Torres J, San Jose E. 2019. Src tyrosine kinase inhibitors: new perspectives on their immune, antiviral, and senotherapeutic potential. Front. Pharmacol. 10: 1011.
    Pubmed PMC
  23. Fuhrmann-Stroissnigg H, Niedernhofer LJ, Robbins PD. 2018. Hsp90 inhibitors as senolytic drugs to extend healthy aging. Cell Cycle 17: 1048-1055.
    Pubmed PMC
  24. Geng X, Wang F, Tian D, Huang L, Streator E, Zhu J, et al. 2020. Cardiac glycosides inhibit cancer through Na/K-ATPase-dependent cell death induction. Biochem. Pharmacol. 182: 114226.
    Pubmed PMC
  25. Oliver PL, Finelli MJ, Edwards B, Bitoun E, Butts DL, Becker EB, et al. 2011. Oxr1 is essential for protection against oxidative stressinduced neurodegeneration. PLoS Genet. 7: e1002338.
    Pubmed PMC
  26. Yang M, Luna L, Sorbo JG, Alseth I, Johansen RF, Backe PH, et al. 2014. Human OXR1 maintains mitochondrial DNA integrity and counteracts hydrogen peroxide-induced oxidative stress by regulating antioxidant pathways involving p21. Free Radic. Biol. Med. 77: 41-48.
    Pubmed
  27. Wang R, Yu Z, Sunchu B, Shoaf J, Dang I, Zhao S, et al. 2017. Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2independent mechanism. Aging Cell 16: 564-574.
    Pubmed PMC
  28. Maduro AT, Luis C, Soares R. 2021. Ageing, cellular senescence and the impact of diet: an overview. Porto Biomed J. 6: e120.
    Pubmed PMC
  29. Hwang HV, Tran DT, Rebuffatti MN, Li CS, Knowlton AA. 2018. Investigation of quercetin and hyperoside as senolytics in adult human endothelial cells. PLoS One 13: e0190374.
    Pubmed PMC
  30. Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, et al. 2018. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine 36: 18-28.
    Pubmed PMC
  31. Malavolta M, Pierpaoli E, Giacconi R, Costarelli L, Piacenza F, Basso A, et al. 2016. Pleiotropic effects of tocotrienols and quercetin on cellular senescence: Introducing the perspective of senolytic effects of phytochemicals. Curr. Drug Targets 17: 447-459.
    Pubmed
  32. Ota H, Kodama A. 2022. Dasatinib plus quercetin attenuates some frailty characteristics in SAMP10 mice. Sci. Rep. 12: 2425.
    Pubmed PMC
  33. Justice JN, Nambiar AM, Tchkonia T, LeBrasseur NK, Pascual R, Hashmi SK, et al. 2019. Senolytics in idiopathic pulmonary fibrosis:Results from a first-in-human, open-label, pilot study. EBioMedicine 40: 554-563.
    Pubmed PMC
  34. Currais A, Farrokhi C, Dargusch R, Armando A, Quehenberger O, Schubert D, et al. 2018. Fisetin reduces the impact of aging on behavior and physiology in the rapidly aging SAMP8 mouse. J. Gerontol. A Biol. Sci. Med. Sci. 73: 299-307.
    Pubmed PMC
  35. Li W, He Y, Zhang R, Zheng G, Zhou D. 2019. The curcumin analog EF24 is a novel senolytic agent. Aging (Albany NY). 11: 771-782.
    Pubmed PMC
  36. Kumar R, Sharma A, Kumari A, Gulati A, Padwad Y, Sharma R. 2019. Epigallocatechin gallate suppresses premature senescence of preadipocytes by inhibition of PI3K/Akt/mTOR pathway and induces senescent cell death by regulation of Bax/Bcl-2 pathway. Biogerontology 20: 171-189.
    Pubmed
  37. Xu Q, Fu Q, Li Z, Liu H, Wang Y, Lin X, et al. 2021. The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice. Nat. Metab. 3: 1706-1726.
    Pubmed PMC
  38. Moaddel R, Rossi M, Rodriguez S, Munk R, Khadeer M, Abdelmohsen K, et al. 2022. Identification of gingerenone A as a novel senolytic compound. PLoS One 17: e0266135.
    Pubmed PMC
  39. Varela-Eirin M, Carpintero-Fernandez P, Sanchez-Temprano A, Varela-Vazquez A, Paino CL, Casado-Diaz A, et al. 2020. Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis. Aging (Albany NY). 12: 15882-15905.
    Pubmed PMC
  40. Zheng D, Liwinski T, Elinav E. 2020. Interaction between microbiota and immunity in health and disease. Cell Res. 30: 492-506.
    Pubmed PMC
  41. Hohman LS, Osborne LC. 2022. A gut-centric view of aging: Do intestinal epithelial cells contribute to age-associated microbiota changes, inflammaging, and immunosenescence? Aging Cell 21: e13700.
    Pubmed PMC
  42. Walrath T, Dyamenahalli KU, Hulsebus HJ, McCullough RL, Idrovo JP, Boe DM, et al. 2021. Age-related changes in intestinal immunity and the microbiome. J. Leukoc. Biol. 109: 1045-1061.
    Pubmed PMC
  43. Ren J, Li H, Zeng G, Pang B, Wang Q, Wei J. 2023. Gut microbiome-mediated mechanisms in aging-related diseases: are probiotics ready for prime time? Front. Pharmacol. 14: 1178596.
    Pubmed PMC
  44. Stebegg M, Silva-Cayetano A, Innocentin S, Jenkins TP, Cantacessi C, Gilbert C, et al. 2019. Heterochronic faecal transplantation boosts gut germinal centres in aged mice. Nat. Commun. 10: 2443.
    Pubmed PMC
  45. Saccon TD, Nagpal R, Yadav H, Cavalcante MB, Nunes ADC, Schneider A, et al. 2021. Senolytic combination of dasatinib and quercetin alleviates intestinal senescence and inflammation and modulates the gut microbiome in aged mice. J. Gerontol. A Biol. Sci. Med. Sci. 76: 1895-1905.
    Pubmed PMC
  46. Ashiqueali SA, Chaudhari D, Zhu X, Noureddine S, Siddiqi S, Garcia DN, et al. 2024. Fisetin modulates the gut microbiota alongside biomarkers of senescence and inflammation in a DSS-induced murine model of colitis. Geroscience 46: 3085-3103.
    Pubmed PMC
  47. Wei R, Su Z, Mackenzie GG. 2023. Chlorogenic acid combined with epigallocatechin-3-gallate mitigates D-galactose-induced gut aging in mice. Food Funct. 14: 2684-2697.
    Pubmed
  48. Sharma R, Kumar R, Sharma A, Goel A, Padwad Y. 2022. Long-term consumption of green tea EGCG enhances murine health span by mitigating multiple aspects of cellular senescence in mitotic and post-mitotic tissues, gut dysbiosis, and immunosenescence. J. Nutr. Biochem. 107: 109068.
    Pubmed
  49. Wang X, Wang P, Li Y, Guo H, Wang R, Liu S, et al. 2024. Procyanidin C1 modulates the microbiome to increase FOXO1 signaling and valeric acid levels to protect the mucosal barrier in inflammatory bowel disease. Engineering doi.org/10.1016/j.eng.2023.10.016.
  50. Zhao Q, Yu J, Hao Y, Zhou H, Hu Y, Zhang C, et al. 2023. Akkermansia muciniphila plays critical roles in host health. Crit Rev Microbiol. 49: 82-100.
    Pubmed
  51. Chen TJ, Feng Y, Liu T, Wu TT, Chen YJ, Li X, et al. 2020. Fisetin regulates gut microbiota and exerts neuroprotective effect on mouse model of Parkinson's disease. Front. Neurosci. 14: 549037.
    Pubmed PMC
  52. Huang S, Chen J, Cui Z, Ma K, Wu D, Luo J, et al. 2023. Lachnospiraceae-derived butyrate mediates protection of high fermentable fiber against placental inflammation in gestational diabetes mellitus. Sci. Adv. 9: eadi7337.
    Pubmed PMC
  53. Sharma R. 2022. Emerging interrelationship between the gut microbiome and cellular senescence in the context of aging and disease:perspectives and therapeutic opportunities. Probiotics Antimicrob. Proteins 14: 648-663.
    Pubmed PMC

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Article

Review

J. Microbiol. Biotechnol. 2024; 34(11): 2166-2172

Published online November 28, 2024 https://doi.org/10.4014/jmb.2408.08032

Copyright © The Korean Society for Microbiology and Biotechnology.

Impacts of Senolytic Phytochemicals on Gut Microbiota: A Comprehensive Review

Hee Soo Kim1,2 and Chang Hwa Jung1,2*

1Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
2Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do 55365, Republic of Korea

Correspondence to:Chang Hwa Jung,       chjung@kfri.re.kr

Received: August 19, 2024; Revised: October 21, 2024; Accepted: October 29, 2024

Abstract

There is increasing interest in utilizing senolytics to selectively remove senescent cells from intestinal tissues, with the aim of maintaining a healthy gut environment during aging. This strategy underscores the potential of senolytics to enhance gut health by delaying intestinal aging and positively modulating gut microbiota. Certain plant-based phytochemicals have demonstrated promising senolytic effects. Beyond their ability to eliminate senescent cells, these compounds also exhibit antioxidant and anti-inflammatory properties, reducing oxidative stress and inflammation-key drivers of age-related diseases. By selectively removing senescent cells from the intestine, senolytic phytochemicals contribute to an improved intestinal inflammatory environment and promote the growth of a diverse microbial community. Ultimately, the dietary intake of these senolytic phytochemicals aids in maintaining a healthier intestinal microenvironment by targeting and clearing aged enterocytes.

Keywords: Senolytic, senescence, aging, gut, phytochemical

References

  1. Lopes-Paciencia S, Saint-Germain E, Rowell MC, Ruiz AF, Kalegari P, Ferbeyre G. 2019. The senescence-associated secretory phenotype and its regulation. Cytokine 117: 15-22.
    Pubmed
  2. Lujambio A, Akkari L, Simon J, Grace D, Tschaharganeh DF, Bolden JE, et al. 2013. Non-cell-autonomous tumor suppression by p53. Cell 153: 449-460.
    Pubmed KoreaMed
  3. Gasek NS, Kuchel GA, Kirkland JL, Xu M. 2021. Strategies for targeting senescent cells in human disease. Nat. Aging 1: 870-879.
    Pubmed KoreaMed
  4. Chandeck C, Mooi WJ. 2010. Oncogene-induced cellular senescence. Adv. Anat. Pathol. 17: 42-48.
    Pubmed
  5. Nousis L, Kanavaros P, Barbouti A. 2023. Oxidative stress-induced cellular senescence: is labile iron the connecting link? Antioxidants (Basel) 12: 1250.
    Pubmed KoreaMed
  6. Miwa S, Kashyap S, Chini E, von Zglinicki T. 2022. Mitochondrial dysfunction in cell senescence and aging. J. Clin. Invest. 132:e158774.
    Pubmed KoreaMed
  7. Peng X, Wu Y, Brouwer U, van Vliet T, Wang B, Demaria M, et al. 2020. Cellular senescence contributes to radiation-induced hyposalivation by affecting the stem/progenitor cell niche. Cell Death Dis. 11: 854.
    Pubmed KoreaMed
  8. Guillon J, Petit C, Toutain B, Guette C, Lelievre E, Coqueret O. 2019. Chemotherapy-induced senescence, an adaptive mechanism driving resistance and tumor heterogeneity. Cell Cycle 18: 2385-2397.
    Pubmed KoreaMed
  9. Soto-Gamez A, Quax WJ, Demaria M. 2019. Regulation of survival networks in senescent cells: From mechanisms to interventions. J. Mol. Biol. 431: 2629-2643.
    Pubmed
  10. Hickson LJ, Langhi Prata LGP, Bobart SA, Evans TK, Giorgadze N, Hashmi SK, et al. 2019. Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine 47: 446-456.
    Pubmed KoreaMed
  11. Chen J. 2016. The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harb. Perspect. Med. 6: a026104.
    Pubmed KoreaMed
  12. Seluanov A, Gorbunova V, Falcovitz A, Sigal A, Milyavsky M, Zurer I, et al. 2001. Change of the death pathway in senescent human fibroblasts in response to DNA damage is caused by an inability to stabilize p53. Mol. Cell Biol. 21: 1552-1564.
    Pubmed KoreaMed
  13. Zhu Y, Tchkonia T, Pirtskhalava T, Gower AC, Ding H, Giorgadze N, et al. 2015. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14: 644-658.
    Pubmed KoreaMed
  14. Fuhrmann-Stroissnigg H, Ling YY, Zhao J, McGowan SJ, Zhu Y, Brooks RW, et al. 2017. Identification of HSP90 inhibitors as a novel class of senolytics. Nat. Commun. 8: 422.
    Pubmed KoreaMed
  15. Zhu Y, Tchkonia T, Fuhrmann-Stroissnigg H, Dai HM, Ling YY, Stout MB, et al. 2016. Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell 15: 428-435.
    Pubmed KoreaMed
  16. Zhu Y, Doornebal EJ, Pirtskhalava T, Giorgadze N, Wentworth M, Fuhrmann-Stroissnigg H, et al. 2017. New agents that target senescent cells: the flavone, fisetin, and the BCL-X(L) inhibitors, A1331852 and A1155463. Aging (Albany NY) 9: 955-963.
    Pubmed KoreaMed
  17. Huang B, Vassilev LT. 2009. Reduced transcriptional activity in the p53 pathway of senescent cells revealed by the MDM2 antagonist nutlin-3. Aging (Albany NY) 1: 845-854.
    Pubmed KoreaMed
  18. Baar MP, Brandt RMC, Putavet DA, Klein JDD, Derks KWJ, Bourgeois BRM, et al. 2017. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell 169: 132-147 e116.
    Pubmed KoreaMed
  19. Nogueira V, Park Y, Chen CC, Xu PZ, Chen ML, Tonic I, et al. 2008. Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosis. Cancer Cell 14: 458-470.
    Pubmed KoreaMed
  20. Schlessinger J. 2000. New roles for Src kinases in control of cell survival and angiogenesis. Cell 100: 293-296.
    Pubmed
  21. Anerillas C, Herman AB, Rossi M, Munk R, Lehrmann E, Martindale JL, et al. 2022. Early SRC activation skews cell fate from apoptosis to senescence. Sci. Adv. 8: eabm0756.
    Pubmed KoreaMed
  22. Rivera-Torres J, San Jose E. 2019. Src tyrosine kinase inhibitors: new perspectives on their immune, antiviral, and senotherapeutic potential. Front. Pharmacol. 10: 1011.
    Pubmed KoreaMed
  23. Fuhrmann-Stroissnigg H, Niedernhofer LJ, Robbins PD. 2018. Hsp90 inhibitors as senolytic drugs to extend healthy aging. Cell Cycle 17: 1048-1055.
    Pubmed KoreaMed
  24. Geng X, Wang F, Tian D, Huang L, Streator E, Zhu J, et al. 2020. Cardiac glycosides inhibit cancer through Na/K-ATPase-dependent cell death induction. Biochem. Pharmacol. 182: 114226.
    Pubmed KoreaMed
  25. Oliver PL, Finelli MJ, Edwards B, Bitoun E, Butts DL, Becker EB, et al. 2011. Oxr1 is essential for protection against oxidative stressinduced neurodegeneration. PLoS Genet. 7: e1002338.
    Pubmed KoreaMed
  26. Yang M, Luna L, Sorbo JG, Alseth I, Johansen RF, Backe PH, et al. 2014. Human OXR1 maintains mitochondrial DNA integrity and counteracts hydrogen peroxide-induced oxidative stress by regulating antioxidant pathways involving p21. Free Radic. Biol. Med. 77: 41-48.
    Pubmed
  27. Wang R, Yu Z, Sunchu B, Shoaf J, Dang I, Zhao S, et al. 2017. Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2independent mechanism. Aging Cell 16: 564-574.
    Pubmed KoreaMed
  28. Maduro AT, Luis C, Soares R. 2021. Ageing, cellular senescence and the impact of diet: an overview. Porto Biomed J. 6: e120.
    Pubmed KoreaMed
  29. Hwang HV, Tran DT, Rebuffatti MN, Li CS, Knowlton AA. 2018. Investigation of quercetin and hyperoside as senolytics in adult human endothelial cells. PLoS One 13: e0190374.
    Pubmed KoreaMed
  30. Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, et al. 2018. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine 36: 18-28.
    Pubmed KoreaMed
  31. Malavolta M, Pierpaoli E, Giacconi R, Costarelli L, Piacenza F, Basso A, et al. 2016. Pleiotropic effects of tocotrienols and quercetin on cellular senescence: Introducing the perspective of senolytic effects of phytochemicals. Curr. Drug Targets 17: 447-459.
    Pubmed
  32. Ota H, Kodama A. 2022. Dasatinib plus quercetin attenuates some frailty characteristics in SAMP10 mice. Sci. Rep. 12: 2425.
    Pubmed KoreaMed
  33. Justice JN, Nambiar AM, Tchkonia T, LeBrasseur NK, Pascual R, Hashmi SK, et al. 2019. Senolytics in idiopathic pulmonary fibrosis:Results from a first-in-human, open-label, pilot study. EBioMedicine 40: 554-563.
    Pubmed KoreaMed
  34. Currais A, Farrokhi C, Dargusch R, Armando A, Quehenberger O, Schubert D, et al. 2018. Fisetin reduces the impact of aging on behavior and physiology in the rapidly aging SAMP8 mouse. J. Gerontol. A Biol. Sci. Med. Sci. 73: 299-307.
    Pubmed KoreaMed
  35. Li W, He Y, Zhang R, Zheng G, Zhou D. 2019. The curcumin analog EF24 is a novel senolytic agent. Aging (Albany NY). 11: 771-782.
    Pubmed KoreaMed
  36. Kumar R, Sharma A, Kumari A, Gulati A, Padwad Y, Sharma R. 2019. Epigallocatechin gallate suppresses premature senescence of preadipocytes by inhibition of PI3K/Akt/mTOR pathway and induces senescent cell death by regulation of Bax/Bcl-2 pathway. Biogerontology 20: 171-189.
    Pubmed
  37. Xu Q, Fu Q, Li Z, Liu H, Wang Y, Lin X, et al. 2021. The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice. Nat. Metab. 3: 1706-1726.
    Pubmed KoreaMed
  38. Moaddel R, Rossi M, Rodriguez S, Munk R, Khadeer M, Abdelmohsen K, et al. 2022. Identification of gingerenone A as a novel senolytic compound. PLoS One 17: e0266135.
    Pubmed KoreaMed
  39. Varela-Eirin M, Carpintero-Fernandez P, Sanchez-Temprano A, Varela-Vazquez A, Paino CL, Casado-Diaz A, et al. 2020. Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis. Aging (Albany NY). 12: 15882-15905.
    Pubmed KoreaMed
  40. Zheng D, Liwinski T, Elinav E. 2020. Interaction between microbiota and immunity in health and disease. Cell Res. 30: 492-506.
    Pubmed KoreaMed
  41. Hohman LS, Osborne LC. 2022. A gut-centric view of aging: Do intestinal epithelial cells contribute to age-associated microbiota changes, inflammaging, and immunosenescence? Aging Cell 21: e13700.
    Pubmed KoreaMed
  42. Walrath T, Dyamenahalli KU, Hulsebus HJ, McCullough RL, Idrovo JP, Boe DM, et al. 2021. Age-related changes in intestinal immunity and the microbiome. J. Leukoc. Biol. 109: 1045-1061.
    Pubmed KoreaMed
  43. Ren J, Li H, Zeng G, Pang B, Wang Q, Wei J. 2023. Gut microbiome-mediated mechanisms in aging-related diseases: are probiotics ready for prime time? Front. Pharmacol. 14: 1178596.
    Pubmed KoreaMed
  44. Stebegg M, Silva-Cayetano A, Innocentin S, Jenkins TP, Cantacessi C, Gilbert C, et al. 2019. Heterochronic faecal transplantation boosts gut germinal centres in aged mice. Nat. Commun. 10: 2443.
    Pubmed KoreaMed
  45. Saccon TD, Nagpal R, Yadav H, Cavalcante MB, Nunes ADC, Schneider A, et al. 2021. Senolytic combination of dasatinib and quercetin alleviates intestinal senescence and inflammation and modulates the gut microbiome in aged mice. J. Gerontol. A Biol. Sci. Med. Sci. 76: 1895-1905.
    Pubmed KoreaMed
  46. Ashiqueali SA, Chaudhari D, Zhu X, Noureddine S, Siddiqi S, Garcia DN, et al. 2024. Fisetin modulates the gut microbiota alongside biomarkers of senescence and inflammation in a DSS-induced murine model of colitis. Geroscience 46: 3085-3103.
    Pubmed KoreaMed
  47. Wei R, Su Z, Mackenzie GG. 2023. Chlorogenic acid combined with epigallocatechin-3-gallate mitigates D-galactose-induced gut aging in mice. Food Funct. 14: 2684-2697.
    Pubmed
  48. Sharma R, Kumar R, Sharma A, Goel A, Padwad Y. 2022. Long-term consumption of green tea EGCG enhances murine health span by mitigating multiple aspects of cellular senescence in mitotic and post-mitotic tissues, gut dysbiosis, and immunosenescence. J. Nutr. Biochem. 107: 109068.
    Pubmed
  49. Wang X, Wang P, Li Y, Guo H, Wang R, Liu S, et al. 2024. Procyanidin C1 modulates the microbiome to increase FOXO1 signaling and valeric acid levels to protect the mucosal barrier in inflammatory bowel disease. Engineering doi.org/10.1016/j.eng.2023.10.016.
  50. Zhao Q, Yu J, Hao Y, Zhou H, Hu Y, Zhang C, et al. 2023. Akkermansia muciniphila plays critical roles in host health. Crit Rev Microbiol. 49: 82-100.
    Pubmed
  51. Chen TJ, Feng Y, Liu T, Wu TT, Chen YJ, Li X, et al. 2020. Fisetin regulates gut microbiota and exerts neuroprotective effect on mouse model of Parkinson's disease. Front. Neurosci. 14: 549037.
    Pubmed KoreaMed
  52. Huang S, Chen J, Cui Z, Ma K, Wu D, Luo J, et al. 2023. Lachnospiraceae-derived butyrate mediates protection of high fermentable fiber against placental inflammation in gestational diabetes mellitus. Sci. Adv. 9: eadi7337.
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