Is There A Way to Prevent Aging? A Study Using Metformin in Blood Sugar Levels and Serum Levels of IGF-1

Arlina Wiyata Gama; Arief Santoso; Ika Yustisia; Nurpudji Astuti Taslim; Irfan Idris; Isra Wahid

doi:10.24252/al-sihah.v13i1.21694

Arlina Wiyata Gama Bagian Ilmu Biomedik, Universitas Hasanuddin, Makassar
(ID)
Arief Santoso Bagian Ilmu Biomedik, Universitas Hasanuddin, Makassar
(ID)
Ika Yustisia Bagian Ilmu Biomedik, Universitas Hasanuddin, Makassar
(ID) http://orcid.org/0000-0001-7611-968X
Nurpudji Astuti Taslim Bagian Ilmu Biomedik, Universitas Hasanuddin, Makassar
(ID) http://orcid.org/0000-0003-1349-5367
Irfan Idris Bagian Ilmu Biomedik, Universitas Hasanuddin, Makassar
(ID) http://orcid.org/0000-0002-7350-8687
Isra Wahid Bagian Ilmu Biomedik, Universitas Hasanuddin, Makassar
(ID) http://orcid.org/0000-0002-6642-1401

DOI: https://doi.org/10.24252/al-sihah.v13i1.21694

Abstract

Aging is influenced by lifestyle, which one is by consuming excessive calories. In recent years there have been many studies on aging and age-related diseases, calorie restriction mimetic is one of them. Metformin is a calorie restriction mimetic that is attractive to gerontologists. This research analyzed the effect of metformin as a calorie restriction mimetic on fasting blood glucose and IGF-1 serum levels in old white male Wistar rats. This study conducted with an experimental study with a pre and post-test pattern with controlled group design on male rats (Rattus novergicus) Wistar strain which was divided into 3 groups, control group (K), the calorie restriction group (P1), and the metformin group (P2), 6 rats each group. Blood glucose levels were measured by a glucometer and serum IGF-1 levels were measured with an ELISA kit, where blood samples were taken from the tail of the rats. In general, the provision of metformin and calorie restriction tended to reduce blood glucose levels, but increased serum IGF-1 levels. There is a significant relationship between blood glucose levels and serum IGF-1 levels. It’s necessary to conduct further research to determine the effective dose and maximum dose of metformin to reduce blood glucose level and serum IG-1 levels which can be slow down the aging process.

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References

Adams, P. D., Jasper, H., & Rudolph, K. L. (2015). Aging-induced stem cell mutations as drivers for disease and cancer. Cell stem cell, 16(6), 601-612. https://doi.org/10.1016/j.stem.2015.05.002

Al-Goblan, A. S., Al-Alfi, M. A., & Khan, M. Z. (2014). Mechanism linking diabetes mellitus and obesity. Diabetes, metabolic syndrome and obesity: targets and therapy, 7, 587. https://dx.doi.org/10.2147%2FDMSO.S67400

Anderson, R. M., & Weindruch, R. (2012). The caloric restriction paradigm: implications for healthy human aging. American Journal of Human Biology, 24(2), 101-106. https://doi.org/10.1002/ajhb.22243

Arai, Y., Kamide, K., & Hirose, N. (2019). Adipokines and aging: findings from centenarians and the very old. Frontiers in endocrinology, 10, 142. https://doi.org/10.3389/fendo.2019.00142

Balasubramanian, P., Howell, P. R., & Anderson, R. M. (2017). Aging and caloric restriction research: a biological perspective with translational potential. EBioMedicine, 21, 37-44. https://doi.org/10.1016/j.ebiom.2017.06.015

Barzilai, N., Crandall, J. P., Kritchevsky, S. B., & Espeland, M. A. (2016). Metformin as a tool to target aging. Cell metabolism, 23(6), 1060-1065. https://doi.org/10.1016/j.cmet.2016.05.011

Berryman, D. E., Christiansen, J. S., Johannsson, G., Thorner, M. O., & Kopchick, J. J. (2008). Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models. Growth Hormone & IGF Research, 18(6), 455-471. https://doi.org/10.1016/j.ghir.2008.05.005

Blokh, D., & Stambler, D. A. (2012). The intersection between aging and cardiovascular disease. Circulation research, 110(8), 1097-1108.

Blokh, D., & Stambler, I. (2015). Information theoretical analysis of aging as a risk factor for heart disease. Aging and disease, 6(3), 196.

Burch, J. B., Augustine, A. D., Frieden, L. A., Hadley, E., Howcroft, T. K., Johnson, R., & Wise, B. C. (2014). Advances in geroscience: impact on healthspan and chronic disease. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 69(Suppl_1), S1-S3. https://doi.org/10.1093/gerona/glu041

Čepelak, I., Dodig, S., & Dodig, D. C. (2019). Aging, Calorie Restriction and Calorie Restriction Mimetics. Rad Hrvatske akademije znanosti i umjetnosti. Medicinske znanosti, (540= 48-49), 41-50. https://doi.org/10.21857/9e31lhnddm

Cerf, M. E. (2013). Beta cell dysfunction and insulin resistance. Frontiers in endocrinology, 4, 37. https://doi.org/10.3389/fendo.2013.00037

Gillespie, Z. E., Pickering, J., & Eskiw, C. H. (2016). Better living through chemistry: caloric restriction (CR) and CR mimetics alter genome function to promote increased health and lifespan. Frontiers in Genetics, 7, 142. https://doi.org/10.3389/fgene.2016.00142

Graham, N. A., Tahmasian, M., Kohli, B., Komisopoulou, E., Zhu, M., Vivanco, I., & Graeber, T. G. (2012). Glucose deprivation activates a metabolic and signaling amplification loop leading to cell death. Molecular systems biology, 8(1), 589. https://doi.org/10.1038/msb.2012.20

Guerville, F., Barreto, P. D. S., Ader, I., Andrieu, S., Casteilla, L., Dray, C., & Vellas, B. (2020). Revisiting the hallmarks of aging to identify markers of biological age. The Journal of prevention of Alzheimer's disease, 7(1), 56-64. https://doi.org/10.14283/jpad.2019.50

Harianja, E., Widijanti, A., Arsana, P. M., & Handono, K. (2018). Pengaruh Restriksi Kalori Terhadap Kadar Hidrogen Peroksida Dan Kadar Glukosa Darah Pada Tikus Tua. Indonesian Journal Of Clinical Pathology And Medical Laboratory, 14(1), 24-27. http://dx.doi.org/10.24293/ijcpml.v14i1.921

Johnson, M. (2012). Laboratory mice and rats. Labome. http://dx.doi.org/10.13070/mm.en.2.113

Lee, P. G., & Halter, J. B. (2017). The pathophysiology of hyperglycemia in older adults: clinical considerations. Diabetes Care, 40(4), 444-452. https://doi.org/10.2337/dc16-1732

Lee, S. H., & Min, K. J. (2013). Caloric restriction and its mimetics. BMB reports, 46(4), 181. https://dx.doi.org/10.5483%2FBMBRep.2013.46.4.033

Li P., Sun X., Cai G., & Chen X. (2017). Insulin-like Growth Factor System and Aging. Journal of Aging Science. 5(1). 1-5. https://doi.org/10.4172/2329-8847.1000171

Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. Aging cell, 14(4), 497-510. https://doi.org/10.1111/acel.12338

López‐Lluch, G., & Navas, P. (2016). Calorie restriction as an intervention in ageing. The Journal of physiology, 594(8), 2043-2060. https://doi.org/10.1113/JP270543

López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217. https://doi.org/10.1016/j.cell.2013.05.039

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. https://doi.org/10.1016/j.cmet.2019.01.018

Madiraju, A. K., Qiu, Y., Perry, R. J., Rahimi, Y., Zhang, X. M., Zhang, D., & Shulman, G. I. (2018). Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo. Nature medicine, 24(9), 1384-1394. https://doi.org/10.1038/s41591-018-0125-4

Mustika, A., Indrawati, R., & Sari, G. M. (2017). Efek Ekstrak Daun Singawalang (Petiveria alliacea) dalam Menurunkan Kadar Glukosa Darah melalui Peningkatan Ekspresi AMPK-α1 pada Tikus Model Diabetes Melitus. Jurnal Farmasi Klinik Indonesia, 6(1), 22-31. https://doi.org/10.15416/ijcp.2017.6.1.22

Nangoy, B. N., de Queljoe, E., & Yudistira, A. (2019). Uji Aktivitas Antidiabetes Dari Ekstrak Daun Sesewanua (Clerodendron squamatum Vahl.) Terhadap Tikus Putih Jantan Galur Wistar (Rattus norvegicus L.). Pharmacon, 8(4), 774-780. https://doi.org/10.35799/pha.8.2019.29353

Niccoli, T., & Partridge, L. (2012). Ageing as a risk factor for disease. Current biology, 22(17), R741-R752. https://doi.org/10.1016/j.cub.2012.07.024

Pan, H., & Finkel, T. (2017). Key proteins and pathways that regulate lifespan. Journal of Biological Chemistry, 292(16), 6452-6460. https://doi.org/10.1074/jbc.R116.771915

Paolisso, G., Barbieri, M., Bonafe, M., & Franceschi, C. (2000). Metabolic age modelling: the lesson from centenarians. European journal of clinical investigation, 30(10), 888-894. https://doi.org/10.1046/j.1365-2362.2000.00729.x

Phillipson, O. T. (2014). Management of the aging risk factor for Parkinson's disease. Neurobiology of aging, 35(4), 847-857.

Podhorecka, M., Ibanez, B., & Dmoszyńska, A. (2017). Metformin-its potential anti-cancer and anti-aging effects. Advances in Hygiene & Experimental Medicine/Postepy Higieny i Medycyny Doswiadczalnej, 71. https://doi.org/10.4161/cc.26928

Smith Jr, D. L., Elam Jr, C. F., Mattison, J. A., Lane, M. A., Roth, G. S., Ingram, D. K., & Allison, D. B. (2010). Metformin supplementation and life span in Fischer-344 rats. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 65(5), 468-474. https://doi.org/10.1093/gerona/glq033

Solon-Biet, S. M., Mitchell, S. J., de Cabo, R., Raubenheimer, D., Le Couteur, D. G., & Simpson, S. J. (2015). Macronutrients and caloric intake in health and longevity. The Journal of endocrinology, 226(1), R17. https://dx.doi.org/10.1530%2FJOE-15-0173

Sonntag, W. E., Lynch, C. D., Cefalu, W. T., Ingram, R. L., Bennett, S. A., Thornton, P. L., & Khan, A. S. (1999). Pleiotropic effects of growth hormone and insulin-like growth factor (IGF)-1 on biological aging: inferences from moderate caloric-restricted animals. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 54(12), B521-B538. https://doi.org/10.1093/gerona/54.12.B521

Stekovic, S., Hofer, S. J., Tripolt, N., Aon, M. A., Royer, P., Pein, L., & Madeo, F. (2019). Alternate day fasting improves physiological and molecular markers of aging in healthy, non-obese humans. Cell metabolism, 30(3), 462-476. https://doi.org/10.1016/j.cmet.2019.07.016

Vitale, G., Salvioli, S., & Franceschi, C. (2013). Oxidative stress and the ageing endocrine system. Nature Reviews Endocrinology, 9(4), 228-240. https://doi.org/10.1038/nrendo.2013.29

Wati, A., Kosman, R., & Lizikri, A. (2014). Perbandingan Efektivitas Hipoglikemik Obat Metformin Paten Dan Generik Berlogo Berdasarkan Penurunan Kadar Glukosa Darah Mencit (Mus Musculus) Jantan Yang Diinduksi Aloksan. As-Syifaa Jurnal Farmasi, 6(1), 91-97. https://doi.org/10.33096/jifa.v6i1.37

Xia, S., Zhang, X., Zheng, S., Khanabdali, R., Kalionis, B., Wu, J., & Tai, X. (2016). An update on inflamm-aging: mechanisms, prevention, and treatment. Journal of immunology research, 2016. https://doi.org/10.1155/2016/8426874

Yudiarto, F. L., & Sjahrir, H. (2011). Proses Penuaan Otak–Bagaimana Kita Bisa Mencegahnya?. Neurona : 28 (2) http://www.neurona.web.id/paper-detail.do?id=762