Urolıthın A And The Current Approach To The Health Of The Elderly

Öz

The proportion of the elderly population in the world is increasing every year. As accepted by the World Health Organization (WHO), early old age between the ages of 65-75, middle age between the ages of 75-85, and advanced old age after 85 years (1). According to the United Nations world population estimates, the world population for 2022 is estimated to be 7 billion 975 million 105 thousand 156 people, while the elderly population is 782 million 998 thousand 642 people. According to these estimates, 9.8% of the world's population was composed of the elderly population. The top three countries with the highest proportion of elderly population were Japan with 29.9%, Italy with 24.1% and Finland with 23.3%. Turkey ranked 66th among 184 countries. While the rate of population aged 65 and over was 9.9% in 2022, it is expected to increase to 11.0% in 2025 (2). Aging is chronological, biological, characteristic, psychological, socio-cultural, economic and social classified by different sizes. Today, parallel to the increase in the elderly population, increasing diseases related to aging have become a serious public health problem. Improving the life expectancy and quality of life of the aging population is the main aim of current studies (3). With the increase in preventive health services in recent years, the average life expectancy in the elderly and the prevalence of neurodegenerative diseases have increased accordingly. Neurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration and/or death of nerve cells. Dementias are the most common of the neurodegenerative diseases and represent approximately 60-70% of Alzheimer's dementia cases (4). The worldwide prevalence of dementia is around 50 million. According to the 2015 World Alzheimer's Report, the odds of developing some form of dementia in an older adult rises from 2-4% at age 65 to 15% at age 80. As the population ages, current estimates predict more than 130 million cases by 2050 (5). According to Turkey's death and cause of death statistics, the number of elderly people who lost their lives due to Alzheimer's disease increased from 13 thousand 642 in 2017 to 12 thousand 239 in 2021 (2). With advancing age, many physiological changes occur in the organism and the risk of non-communicable diseases such as heart and respiratory diseases, cancer and diabetes increases. Due to inflammation, metabolic syndrome and cardiovascular diseases are frequently seen in the elderly (6). Chronic diseases, which have been reported as a serious health problem in the 21st century by the United Nations and the World Health Organization, are considered among the important causes of death all over the world. It is estimated by the World Health Organization that 75% of deaths in 2020 will be caused by chronic diseases (1). It has been reported by the Turkish Statistical Institute (2021) that 37.6% of individuals aged 65 and over died due to circulatory system diseases, 15.0% due to respiratory system diseases and 12.0% due to benign or malignant tumors (2). Improving the life expectancy and quality of life of the aging population is the main objective of current studies. In recent years, human gut microbiota-targeted aging management has been considered as a new approach to health and prevention of aging (7). Nutrition is the most important factor in providing adequate cognitive and physical functions and minimizing the risks of chronic diseases in elderly individuals. Functional foods have an important place in a healthy and balanced diet and contribute to reducing the risks of diet-related diseases (8). Some of these functional foods are pomegranate, strawberry and hazelnut. Urolithin A, a natural compound, is produced in the intestines from polyphenols such as ellagitannins and ellagic acid found in these foods. Urolithin A is the metabolite compound produced from the conversion of ellagitannins by intestinal bacteria. Urolithin A (UroA) has positive effects on aging and age-related diseases by reducing inflammation, improving mitochondrial function and activating mitophagy (9). Urolithins are produced from foods containing ellagic acid that undergo intestinal microbial transformation, and their concentrations vary between individuals (10).

Anahtar Kelimeler

• Urolithin A
• Healthy Aging
• Functional Nutrients.

Urolithin a ve yaşlı sağlığına güncel yaklaşım

Öz

Anahtar Kelimeler

• Urolithin A
• Sağlıklı yaşlanma
• Fonksiyonel besinler

Kaynakça

1. World Health Organization (WHO). (2014). Noncommunicable Diseases Country Profiles 2011. https://apps.who.int/iris/handle/10665/44704
2. Türkiye İstatistik Kurumu. (2023). İstatistiklerle Yaşlılar,2022. https://data.tuik.gov.tr/Bulten/Index?p=Istatistiklerle-Yaslilar-2021-45636
3. Öksüzokyar, M. M., Eryiğit, S. Ç., & Öğüt, S. (2016). Biyolojik yaşlanma nedenleri ve etkileri. Mehmet Akif Ersoy Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 4(1). https://dergipark.org.tr/en/pub/maeusabed/issue/24655/260781?publisher=mehmetakif
4. Prince, M., Wimo, A., & Prina , M. (2015). World Alzheimer Report 2015. London, Alzheimer’s Disease International. https://unilim.hal.science/hal-03495438/document
5. Patterson, C. (2018). World alzheimer report. https://apo.org.au/node/260056
6. Kubat Bakır, G., & Akın, S. (2019). Yaşlılıkta kronik hastalıkların yönetimi ile ilişkili faktörler. Sağlık ve Toplum, 29(2), 17-25. http://openaccess.maltepe.edu.tr/xmlui/handle/20.500.12415/7860
7. Ling, Z.,Liu, X., & Wu, S. (2022).Gut microbiota and aging. Crit Rev Food Sci Nutr,1,1-56. https://doi.org/10.1080/10408398.2020.1867054
8. Öğüt, S., Polat, M., &Orhan, H. (2008). Isparta ve Burdur huzurevlerinde kalan yaşlıların sosyodemografik durumları ve beslenme tercihleri. Turk Geriatri Dergisi, 11, 82–87. https://www.gidadernegi.org/TR/Genel/2409349551d0e.pdf?DIL=1&BELGEANAH=1612&DOSYAISIM=240934955.pdf

9. Espín, J. C., Larrosa, M., & Tomás-Barberán, F. (2013). Biological significance of urolithins, the gut microbial ellagic acid-derived metabolites: the evidence so far. Evidence-Based Complementary and Alternative Medicine. https://doi.org/10.1155/2013/270418
10. Cerdá, B., Periago, P., & Tomás-Barberán, F. A. (2005). Identification of urolithin A as a metabolite produced by human colon microflora from ellagic acid and related compounds. Journal of Agricultural and Food Chemistry, 53(14), 5571-5576. https://doi.org/10.1021/jf050384i
11. Gimenez-Bastida, J.A., Gonzalez-Sarrıas, A., & Garcıa-Conesa, M. T. (2012). Ellagitannin metabolites, urolithin A glucuronide and its aglycone urolithin A, ameliorate TNF--induced inflammation and associated molecular markers in human aortic endothelial cells. Molekuler Nutrition & Food Research, 56, 784-796. https://doi.org/10.1002/mnfr.201100677
12. Cortés-Martín, A., García-Villalba, R., & 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. https://doi.org/10.1039/C8FO00956B
13. García-Mantrana, I., Calatayud, M., & Collado, M. C. (2019). Urolithin metabotypes can determine the modulation of gut microbiota in healthy individuals by tracking walnuts consumption over three days. Nutrients, 11(10), 2483. https://doi.org/10.3390/nu11102483
14. Selma, M. V., Beltrán, D., & Tomás-Barberán, F. A. (2014). Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species. Food & Function, 5(8), 1779-1784. https://doi.org/10.1039/C4FO00092G
15. Zhang, X., Zhao, A., & Burton-Freeman, B. M. (2020). Functional deficits in gut microbiome of young and middle-aged adults with prediabetes apparent in metabolizing bioactive (Poly) phenols. Nutrients, 12(11), 3595. https://doi.org/10.3390/nu12113595
16. Skledar, D. G., Tomašič, T., & Zega, A. (2019). Evaluation of endocrine activities of ellagic acid and urolithins using reporter gene assays. Chemosphere, 220, 706-713. https://doi.org/10.1016/j.chemosphere.2018.12.185
17. Muku, G. E., Murray, I. A., & Perdew, G. H. (2018). Urolithin A is a dietary microbiota-derived human aryl hydrocarbon receptor antagonist. Metabolites, 8(4), 86. https://doi.org/10.3390/metabo8040086
18. Ávila-Gálvez, M. A., Giménez-Bastida, J. A., & Espín, J. C. (2019). Tissue deconjugation of urolithin A glucuronide to free urolithin A in systemic inflammation. Food & Function, 10(6), 3135-3141. https://doi.org/10.1039/C9FO00298G
19. Toney, A. M., Fan, R., & Chung, S. (2019). Urolithin A, a gut metabolite, improves insulin sensitivity through augmentation of mitochondrial function and biogenesis. Obesity, 27(4), 612-620. https://doi.org/10.1002/oby.22404
20. Kang, I., Buckner, T., & Chung, S. (2016). Improvements in metabolic health with consumption of ellagic acid and subsequent conversion into urolithins: evidence and mechanisms. Advances in Nutrition, 7(5), 961-972. https://advances.nutrition.org/
21. Cerdá, B., Espín, J. C., & Tomás-Barberán, F. A. (2004). The potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy–6H–dibenzopyran–6–one derivatives by the colonic microflora of healthy humans. European Journal of Nutrition, 43(4), 205-220. https://link.springer.com/article/10.1007/s00394-004-0461-7
22. García-Villalba, R., Beltrán, D., & Tomás-Barberán, F. A. (2013). Time course production of urolithins from ellagic acid by human gut microbiota. Journal of Agricultural and Food Chemistry, 61(37), 8797-8806. https://doi.org/10.1021/jf402498b
23. D’Amico, D., Andreux, P. A., & Auwerx, J. (2021). Impact of the natural compound urolithin A on health, disease, and aging. Trends in Molecular Medicine, 27(7), 687-699. https://doi.org/10.1016/j.molmed.2021.04.009
24. López-Otín, C., Blasco, M. A., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217. https://doi.org/10.1016/j.cell.2013.05.039
25. Santanasto, A. J., Coen, P. M.. & Newman, A. B. (2016). The relationship between mitochondrial function and walking performance in older adults with a wide range of physical function. Experimental Gerontology, 81, 1-7. https://doi.org/10.1016/j.exger.2016.04.002
26. Balan, E., Schwalm, C., & Deldicque, L. (2019).Regular endurance exercise promotes fission, mitophagy, and oxidativ phosphorylationin human skeletal muscle independently of age. Frontiersinphysiology, 10, 1088. https://doi.org/10.3389/fphys.2019.01088
27. Ryu, D., Mouchiroud, L., & Auwerx, J. (2016). Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nature Medicine, 22(8), 879-888. https://www.nature.com/articles/nm.4132.
28. Palikaras, K., Lionaki, E., & Tavernarakis, N. (2018). Mechanisms of mitophagy in cellular homeostasis, physiology and pathology. Nature Cell Biology, 20(9), 1013-1022. https://www.nature.com/articles/s41556-018-0176-2
29. Luan, P., D’Amico, D.,& Auwerx, J. (2021). Urolithin A improves muscle function by inducing mitophagy in muscular dystrophy. Science Translational Medicine, 13(588). https://doi.org/10.1126/scitranslmed.abb0319
30. Tuohetaerbaike, B., Zhang, Y., & Li, X. (2020). Pancreas protective effects of Urolithin A on type 2 diabetic mice induced by high fat and streptozotocin via regulating autophagy and AKT/mTOR signaling pathway. Journal of Ethnopharmacology, 250, 112479. https://doi.org/10.1016/j.jep.2019.112479
31. Ploumi, C., Daskalaki, I., & Tavernarakis, N. (2017). Mitochondrial biogenesis and clearance: a balancing act. The FEBS Journal, 284(2), 183-195. https://doi.org/10.1111/febs.13820
32. Andreux, P. A., Blanco-Bose, W., & Rinsch, C. (2019). The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health humans. Nature Metabolism, 1(6), 595-603. https://www.nature.com/articles/s42255-019-0073-4
33. Franceschi, C., Garagnani, P., & Santoro, A. (2018). Inflammaging: a new immune–metabolic viewpoint for age-related diseases. Nature Reviews Endocrinology, 14(10), 576-590. https://www.nature.com/articles/s41574-018-0059-4
34. Singh, A., Andreux, P., & Rinsch, C. (2017). Orally administered urolithin A is safe and modulates muscle and mitochondrial biomarkers in elderly. Innovation in Aging, 1(suppl_1), 1223-1224. https://doi.org/10.1093/geroni/igx004.4446
35. Guada, M., Ganugula, R., & Kumar, M. N. R. (2017). Urolithin A mitigates cisplatin-induced nephrotoxicity by inhibiting renal inflammation and apoptosis in an experimental rat model. Journal of Pharmacology and Experimental Therapeutics, 363(1), 58-65. https://doi.org/10.1124/jpet.117.242420
36. Gong, Z., Huang, J., & Xuan, A. (2019). Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice. Journal of Neuroinflammation, 16(1).https://doi.org/10.1186/s12974-019-1450-3
37. Fang, E. F., Hou, Y.. & Bohr, V. A. (2019). Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease. Nature Neuroscience, 22(3), 401-412. https://www.nature.com/articles/s41593-018-0332-9
38. Di Lorito, C., Long, A., & Van der Wardt, V. (2021). Exercise interventions for older adults: A systematic review of meta-analyses. Journal of Sport and Health Science, 10(1), 29-47. https://doi.org/10.1016/j.jshs.2020.06.003
39. Xia, B., Shi, X. C., & Wu, J. W. (2020). Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice. PLoS Biology, 18(3), e3000688. https://doi.org/10.1371/journal.pbio.3000688
40. Ghosh, N., Das, A.,& Sen, C. K. (2020). Urolithin A augments angiogenic pathways in skeletal muscle by bolstering NAD+ and SIRT1. Scientific Reports, 10(1), 1-13. https://doi.org/10.1038/s41598-020-76564-7
41. Çiftçi, S., & Rakıcıoğlu, N. (2019). Yaşlılarda Kardiyovasküler Hastalıklar ve Beslenme Etmenleri. Beslenme ve Diyet Dergisi, 47(1), 82-90. https://doi.org/10.33076/2019.BDD.1204
42. Tang, L., Mo, Y., & Chen, A. (2017). Urolithin A alleviates myocardial ischemia/reperfusion injury via PI3K/Akt pathway. Biochemical and Biophysical Research Communications, 486(3), 774-780. https://doi.org/10.1016/j.bbrc.2017.03.119
43. Cui, G. H., Chen, W. Q., & Shen, Z. Y. (2018). Urolithin A shows anti-atherosclerotic activity via activation of class B scavenger receptor and activation of Nef2 signaling pathway. Pharmacological Reports, 70(3), 519-524. https://link.springer.com/article/10.1016/j.pharep.2017.04.020
44. Savi, M., Bocchi, L., & Del Rio, D. (2017). In vivo administration of urolithin A and B prevents the occurrence of cardiac dysfunction in streptozotocin-induced diabetic rats. Cardiovascular Diabetology, 16(1), 1-13. https://cardiab.biomedcentral.com/articles/10.1186/s12933-017-0561-3
45. Kumar, A., & Singh, A. (2015) A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacol Reports, 67,195-203. https://doi.org/10.1016/j.pharep.2014.09.004
46. Niu, H., Álvarez-Álvarez, I., & Aguinaga-Ontoso, I. (2017). Prevalence and incidence of Alzheimer's disease in Europe: A meta-analysis. Neurología (English Edition), 32(8), 523-532. https://doi.org/10.1016/j.nrleng.2016.02.009
47. Wan, YW., Al-Ouran, R., &Allison ,K.(2020) Meta-analysis of the Alzheimer’s disease human brain transcriptome and functional dissection in mouse models. Cell Reports, 32,107908. https://doi.org/10.1016/j.celrep.2020.107908
48. Liu, H., Kang, H., & Li, F. (2018). Urolithin A inhibits the catabolic effect of TNFα on nucleus pulposus cell and alleviates intervertebral disc degeneration in vivo. Frontiers in Pharmacology, 9, 1043. https://doi.org/10.3389/fphar.2018.01043
49. Kshirsagar, S., Alvir, R. V., & Reddy, P. H. (2022). A Combination Therapy of Urolithin A+ EGCG Has Stronger Protective Effects than Single Drug Urolithin A in a Humanized Amyloid Beta Knockin Mice for Late-Onset Alzheimer’s Disease. Cells, 11(17), 2660. https://doi.org/10.3390/cells11172660
50. DaSilva, N. A., Nahar, P. P., & Seeram, N. P. (2019). Pomegranate ellagitannin-gut microbial-derived metabolites, urolithins, inhibit neuroinflammation in vitro. Nutritional Neuroscience, 22(3), 185-195. https://doi.org/10.1080/1028415X.2017.1360558
51. Velagapudi, R., Lepiarz, I., & Olajide, O. A. (2019). Induction of autophagy and activation of SIRT‐1 deacetylation mechanisms mediate neuroprotection by the pomegranate metabolite urolithin A in BV2 microglia and differentiated 3D human neural progenitor cells. Molecular Nutrition & Food Research, 63(10), 1801237. https://doi.org/10.1002/mnfr.201801237
52. Chen, P., Chen, F., & Zhou, B. (2019). Activation of the miR-34a-mediated SIRT1/mTOR signaling pathway by urolithin A attenuates D-galactose-induced brain aging in mice. Neurotherapeutics, 16(4), 1269-1282. https://doi.org/10.1007/s13311-019-00753-0
53. Vergroesen, P. P., Kingma, I., & Smit, T. H. (2015). Mechanics and biology in intervertebral disc degeneration: a vicious circle. Osteoarthritis and Cartilage, 23(7), 1057-1070. https://doi.org/10.1016/j.joca.2015.03.028
54. Adams MA, Roughley PJ. (2006): What is intervertebral disc degeneration, and what causes it? Spine (Phila Pa 1976), 31(18),2151-2161. https://journals.lww.com/spinejournal/abstract/2006/08150/what_is_intervertebral_disc_degeneration,_and_what.24.aspx
55. Lin, J., Zhuge, J., & Wang, X. (2020). Urolithin A-induced mitophagy suppresses apoptosis and attenuates intervertebral disc degeneration via the AMPK signaling pathway. Free Radical Biology and Medicine, 150, 109-119. https://doi.org/10.1016/j.freeradbiomed.2020.02.024
56. Fu, X., Gong, L. F., & Yu, K. H. (2019). Urolithin A targets the PI3K/Akt/NF-κB pathways and prevents IL-1β-induced inflammatory response in human osteoarthritis: in vitro and in vivo studies. Food & Function, 10(9), 6135-6146. https://doi.org/10.1039/C9FO01332F
57. Koçhan, K., Erdem, E., & Gönen, C. (2014). Inflamatuvar barsak hastalıklarının aktivite tayininde endoskopik aktivite indeksleri ile laboratuvar parametreleri arasındaki ilişki. Akademik Gastroenteroloji Dergisi, 13(3), 101-106. https://dergipark.org.tr/en/pub/agd/issue/1447/17446
58. Sairenji, T., Collins, K. L., & Evans, D. V. (2017). An update on inflammatory bowel disease. Primary Care: Clinics in Office Practice, 44(4), 673-692. https://doi.org/10.1016/j.pop.2017.07.010
59. Bouchard, J., Acharya, A., & Mehta, R. L. (2015). A prospective international multicenter study of AKI in the intensive care unit. Clinical Journal of the American Society of Nephrology, 10(8), 1324-1331. http://cjasn. asnjournals.org/lookup/suppl/doi:10.2215/CJN.04360514/-/ DCSupplemental
60. Zou, D., Ganugula, R., & Kumar, M. R. (2019). Oral delivery of nanoparticle urolithin A normalizes cellular stress and improves survival in mouse model of cisplatin-induced AKI. American Journal of Physiology-Renal Physiology, 317(5), F1255-F1264. https://doi.org/10.1152/ajprenal.00346.2019
61. Jing, T., Liao, J., & Pan, H. (2019). Protective effect of urolithin a on cisplatin-induced nephrotoxicity in mice via modulation of inflammation and oxidative stress. Food and Chemical Toxicology, 129, 108-114. https://doi.org/10.1016/j.fct.2019.04.031
62. Oğuz, A. (2008). Metabolik sendrom. Klinik Psikofarmakoloji Bülteni, 18(2), 57-61. http://metsend.org/upload/26199-metaboliksendromtedavipdf.pdf