Abstract
Several classes of drugs have been introduced to cellular senescence. Senomorphics that target senescence-associated secretory phenotype and senolytics, which clear senescent cells, have been shown to attenuate ageing impacts. This article introduces the strategies and advances in senomorphics and senolytic treatments of age-related diseases.
References
Attaallah, A., Lenzi, M., Marchionni, S., Bincoletto, G., Cocchi, V., Croco, E., ... & Lorenzini, A. (2020). A pro longevity role for cellular senescence. GeroScience, 42, 867-879.
Aroda, V. R., Knowler, W. C., Crandall, J. P., Perreault, L., Edelstein, S. L., Jeffries, S. L., ... & Diabetes Prevention Program Research Group. (2017). Metformin for diabetes prevention: insights gained from the diabetes prevention program/diabetes prevention program outcomes study. Diabetologia, 60(9), 1601-1611.
Artandi, S. E., Alson, S., Tietze, M. K., Sharpless, N. E., Ye, S., Greenberg, R. A., ... & DePinho, R. A. (2002). Constitutive telomerase expression promotes mammary carcinomas in aging mice. Proceedings of the National Academy of Sciences, 99(12), 8191-8196.
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., ... & Van Deursen, J. M. (2016). Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature, 530(7589), 184-189.
Bernardes de Jesus, B., Vera, E., Schneeberger, K., Tejera, A. M., Ayuso, E., Bosch, F., & Blasco, M. A. (2012). Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO molecular medicine, 4(8), 691-704.
Boccardi V, Paolisso G, Mecocci P. (2016). Nutrition and lifestyle in healthy aging: the telomerase challenge. Aging (Albany NY). 2016 Jan;8(1):12-5. doi: 10.18632/aging.100886. PMID: 26826704; PMCID: PMC4761710.
Campbell, J. M., Bellman, S. M., Stephenson, M. D., & Lisy, K. (2017). Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: a systematic review and meta-analysis. Ageing Research Reviews, 40, 31-44.
Carter, H. N., Kim, Y., Erlich, A. T., Zarrin‐khat, D., & Hood, D. A. (2018). Autophagy and mitophagy flux in young and aged skeletal muscle following chronic contractile activity. The Journal of physiology, 596(16), 3567-3584.
Chilton W, O'Brien B, Charchar F. (2017). Telomeres, Aging and Exercise: Guilty by Association? Int J Mol Sci. 2017 Nov 29;18(12):2573. doi: 10.3390/ijms18122573. PMID: 29186077; PMCID: PMC5751176.
Cortés-Martín, A., García-Villalba, R., González-Sarrías, A., Romo-Vaquero, M., Loria-Kohen, V., Ramírez-de-Molina, A., ... & Espín, J. C. (2018). The gut microbiota urolithin metabotypes revisited: the human metabolism of ellagic acid is mainly determined by aging. Food & function, 9(8), 4100-4106.
Coschigano, K. T., Clemmons, D., Bellush, L. L., & Kopchick, J. J. (2000). Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology, 141(7), 2608-2613.
D’Amico, D., Andreux, P. A., Valdés, P., Singh, A., Rinsch, C., & Auwerx, J. (2021). Impact of the natural compound urolithin A on health, disease, and aging. Trends in molecular medicine, 27(7), 687-699.
Dominici, F. P., Diaz, G. A., Bartke, A., Kopchick, J. J., & Turyn, D. (2000). Compensatory alterations of insulin signal transduction in liver of growth hormone receptor knockout mice. Journal of Endocrinology, 166(3), 579-590.
Fang, Y., Hill, C. M., Darcy, J., Reyes-Ordoñez, A., Arauz, E., McFadden, S., ... & Bartke, A. (2018). Effects of rapamycin on growth hormone receptor knockout mice. Proceedings of the National Academy of Sciences, 115(7), E1495-E1503.
Foscolou, A., Magriplis, E., Tyrovolas, S., Chrysohoou, C., Sidossis, L., Matalas, A. L., ... & Panagiotakos, D. (2019). The association of protein and carbohydrate intake with successful aging: a combined analysis of two epidemiological studies. European journal of nutrition, 58, 807-817.
Gilley, D., & Blackburn, E. H. (1994). Lack of telomere shortening during senescence in Paramecium. Proceedings of the National Academy of Sciences, 91(5), 1955-1958.
Harris, S. E., Martin-Ruiz, C., Von Zglinicki, T., Starr, J. M., & Deary, I. J. (2012). Telomere length and aging biomarkers in 70-year-olds: the Lothian Birth Cohort 1936. Neurobiology of aging, 33(7), 1486-e3.
Hayflick L. (1997). Mortality and immortality at the cellular level. A review. Biochemistry (Mosc). Nov;62(11):1180-90. PMID: 9467840.
Hayflick, L. (2021). The greatest risk factor for the leading cause of death is ignored. Biogerontology, 22(1), 133-141.
Hoeijmakers JH. (2009). DNA damage, aging, and cancer. N Engl J Med. Oct 8;361(15):1475-85. doi: 10.1056/NEJMra0804615. Erratum in: N Engl J Med. 2009 Nov 5;361(19):1914. PMID: 19812404.
Huang, D. D., Yan, X. L., Fan, S. D., Chen, X. Y., Yan, J. Y., Dong, Q. T., ... & Yu, Z. (2020). Nrf2 deficiency promotes the increasing trend of autophagy during aging in skeletal muscle: a potential mechanism for the development of sarcopenia. Aging (Albany NY), 12(7), 5977.
Hughes, B. G., & Hekimi, S. (2016). Different mechanisms of longevity in long-lived mouse and Caenorhabditis elegans mutants revealed by statistical analysis of mortality rates. Genetics, 204(3), 905-920.
Jaba, T. (2022). Dasatinib and quercetin: short-term simultaneous administration yields senolytic effect in humans. Issues and Developments in Medicine and Medical Research Vol. 2, 22-31. doi: https://doi.org/10.9734/bpi/idmmr/v2/15155D
de Jesus, B. B., Schneeberger, K., Vera, E., Tejera, A., Harley, C. B., & Blasco, M. A. (2011). The telomerase activator TA‐65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence. Aging cell, 10(4), 604-621.
Kipshidze, M. (2023a). Age-Related Changes in Proportions of Urolithins A, B, and 0. JUNIOR RESEARCHERS, 1(1), 17-29. DOI: https://doi.org/10.52340/2023.01.01.03
Kipshidze, M., Mazanashvili, V., Gorgaslidze, N., & Gabunia, L. (2023b). Cross-sensitizing effects of Resveratrol and Astaxanthin. JUNIOR RESEARCHERS, 1(1), 142–155. ttps://doi.org/10.52340/2023.01.01.16
Kipshidze, M. (2023c). The controlling of contaminated Air, water, soil and medicinal plant raw materials and Mass Spectrometry . JUNIOR RESEARCHERS, 1(1). https://doi.org/10.52340/2023.01.01.01
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., ... & Lowe, S. W. (2008). Senescence of activated stellate cells limits liver fibrosis. Cell, 134(4), 657-667.
Lucas, J., Hsieh, T. C., Halicka, H. D., Darzynkiewicz, Z., & Wu, J. M. (2018). Upregulation of PD-L1 expression by resveratrol and piceatannol in breast and colorectal cancer cells occurs via HDAC3/p300-mediated NF-κB signaling. International journal of oncology, 53(4), 1469–1480. doi.org/10.3892/ijo.2018.4512
Madeo, F., Carmona-Gutierrez, D., Hofer, S. J., & Kroemer, G. (2019). Caloric restriction mimetics against age-associated disease: targets, mechanisms, and therapeutic potential. Cell metabolism, 29(3), 592-610.
Park, S. S., Seo, Y. K., & Kwon, K. S. (2019). Sarcopenia targeting with autophagy mechanism by exercise. BMB reports, 52(1), 64.
Schafer, M. J., White, T. A., Evans, G., Tonne, J. M., Verzosa, G. C., Stout, M. B., ... & LeBrasseur, N. K. (2016). Exercise prevents diet-induced cellular senescence in adipose tissue. Diabetes, 65(6), 1606-1615.
Sun, N., Yun, J., Liu, J., Malide, D., Liu, C., Rovira, I. I., ... & Finkel, T. (2015). Measuring in vivo mitophagy. Molecular cell, 60(4), 685-696.
Tkemaladze, J. (2023a). Reduction, proliferation, and differentiation defects of stem cells over time: a consequence of selective accumulation of old centrioles in the stem cells?. Molecular Biology Reports, 50(3), 2751-2761.doi: 10.1007/s11033-022-08203-5. Epub 2022 Dec 30. PMID: 36583780
Tkemaladze, J. (2023b). The centriolar hypothesis of differentiation and replicative senescence. Junior Researchers, 1(1). doi: https://doi.org/10.52340/2023.01.01.15
Tkemaladze, J. (2023c). Structure and possible functions of centriolar RNA with reference to the centriolar hypothesis of differentiation and replicative senescence. Junior Researchers, 1(1), 156–170. https://doi.org/10.52340/2023.01.01.17
Tkemaladze, J. (2023d). Cross-Senolytic Effects of Dasatinib and Quercetin in Humans. Georgian Scientists. 5 (3):138-52. https://doi.org/10.52340/2023.05.03.15
Tkemaladze, J. (2023e). Is the selective accumulation of oldest centrioles in stem cells the main cause of organism ageing?. Georgian Scientists, 5(3). https://doi.org/10.52340/2023.05.03.22
Trindade LS, Balduino A, Aigaki T, Heddle JG. Senemorphism: a novel perspective on aging patterns and its implication for diet-related biology. Biogerontology. 2012 Aug;13(4):457-66. doi: 10.1007/s10522-012-9383-6. Epub 2012 May 4. PMID: 22555514; PMCID: PMC3407360.
Walton, R. G., Dungan, C. M., Long, D. E., Tuggle, S. C., Kosmac, K., Peck, B. D., ... & Peterson, C. A. (2019). Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double‐blind, placebo‐controlled, multicenter trial: The MASTERS trial. Aging cell, 18(6), e13039