Does Cardiac Physiology also Take Age in Geriatric Population?

Yıl 2021, Cilt: 4 Sayı: 3, 93 - 102, 31.12.2021

Ebru Gülek Karadüz , Ufuk Yurdalan

https://doi.org/10.47141/geriatrik.1022619

Öz

Aging is a process characterized by a decreasing anabolic metabolism and regeneration capacity of the body, leading to irreversible changes in structure and functions. As the older population increases globally, recent studies have focused on a better understanding of the aging changes in the cardiac structure causing mortality and morbidity. It was proven that physiological changes with aging are the leading risk factor for cardiovascular diseases. This review aims to examine cellular mechanisms and investigate changes in the cardiac structure and physiology with the aging process in light of current information. Many theories explain cellular and molecular changes that play a significant role in aging. Decreased autophagy, increased mitochondrial oxidative stress, telomere length changes, mitochondrial dysfunction, changes in mTOR signals, errors in RNA coding, increase in cardiac fibrosis, altered Insulin Like-Growth Factor is fundamental accepted cellular theories currently. As a result of these processes at the cellular level, the effects of aging are seen as structural-functional differentiations in the myocardium, cardiovascular and nervous systems. Changes in the vascular system begin in endothelial cells, and the loss of vascular elasticity over time paves the way for basic functional changes. In addition, hypertrophy of the myocardium and blockages resulting from autonomic nervous system dysfunction are the most notable changes. Cardiovascular diseases such as cardiac hypertrophy, arrhythmia, and heart failure are the major problems as a result of these changes. Studies have also proven that the incidence of the diseases increases in parallel with age. It is thought that a better understanding of the consequences of the cardiac aging process will contribute to both promoting the healthy aging process and presenting more effective methods in the treatment of cardiovascular diseases for older individuals.

Anahtar Kelimeler

Aging, heart, myocardium, geriatrics

Geriatrik Popülasyonda Kardiyak Fizyoloji de Yaş Alır mı?

Öz

Yaşlanma, vücudun anabolik metabolizmasında ve rejenerasyon kapasitesinde azalma ile karakterize, yapı ve fonksiyonlarda geri dönüşümsüz değişikliklere yol açan bir süreçtir. Dünya üzerinde yaşlı nüfusun her geçen gün artması nedeniyle son yıllardaki çalışmalar, yaşlanma sürecinde mortalite ve morbiditeye sebep olan kardiyak yapıdaki değişikliklerin daha iyi anlaşılması üzerine yoğunlaşmıştır. Bu derlemedeki amaç; kardiyak yaşlanma sürecindeki hücresel mekanizmaları güncel bilgiler ışığında ele alırken, yaşlanma sürecinde görülen kardiyak yapı ve fizyolojisindeki değişimleri de bir arada incelemektir. Kardiyak yaşlanmada rol oynayan hücresel ve moleküler değişimler birçok teori ile açıklanmaktadır. Güncel olarak kardiyak yaşlanma sürecinde rol oynadığı kabul edilen temel hücresel teoriler arasında azalmış otofaji, artmış mitokondrial oksidatif stres, telomer boyundaki değişiklikler, mitokondrial disfonksiyon, mTOR sinyallerindeki değişimler, RNA kodlamalarındaki hatalar, kardiyak fibroziste artış, değişmiş İnsülin Like-Growth Factor gösterilmektedir. Hücre düzeyinde meydana gelen bu süreçler sonucunda ise yaşlanmanın etkileri kardiyovasküler, kalp kası ve sinir sisteminde yapısal-fonksiyonel farklılaşmalar olarak görülür. Vasküler sistemde değişiklikler endotel hücrelerde başlar ve zamanla vasküler elastikiyetin kaybedilmesi temel fonksiyonel değişikliklere zemin hazırlar. Ayrıca miyokardiyumda hipertrofik değişimler, otonom sinir sistemi disfonksiyonu sonucunda gelişen blokajlar en belirgin değişikliklerdir. Kardiyak hipertrofi, aritmi ve kalp yetmezliği gibi kardiyovasküler hastalıklar ise bu değişiklikler sonucunda görülen major problemlerdir. Bu hastalıkların yaşa paralel olarak görülme sıklığında artış gösterdiği de çalışmalarda kanıtlanmıştır. Kardiyak yaşlanma sürecinin daha iyi anlaşılmasının, yaşlı bireylere hem sağlıklı yaşlanma sürecinin teşvik edilmesine hem de kardiyovasküler hastalıkların tedavisinde daha etkin tedavi yöntemlerinin sunulmasına katkı sağlayacağı düşünülmektedir.

Anahtar Kelimeler

yaşlanma, kalp, miyokardiyum, geriatri

Kaynakça

• 1. World Health Organization. Ageing and Health 2021. Available from: https://www.who.int/news-room/fact-sheets/detail/ageing-and-health
• 2. Yan M, Sun S, Xu K, et al. Cardiac Aging: From Basic Research to Therapeutics. Oxid Med Cell Longev. 2021 Mar 9;2021:9570325.
• 3. Lara J, Cooper R, Nissan J, et al. A proposed panel of biomarkers of healthy ageing. BMC Medicine. 2015;13:222.
• 4. Pal R, Singh SN, Chatterjee A, et al. Age-related changes in cardiovascular system, autonomic functions, and levels of BDNF of healthy active males: role of yogic practice. Age (Dordrecht, Netherlands). 2014;36(4):9683.
• 5. Alama M. Aging-Related Changes of the Cardiovascular System. Journal of Health and Environmental Research. 2017;3(2):27.
• 6. Zoghi M. Functions of Cardiovascular in the elderly. Turkish Journal of Geriatrics. 2010 ;2 :1-4.
• 7. Chiao YA, Rabinovitch PS. The Aging Heart. Cold Spring Harbor Perspectives in Medicine. 2015;5(9):a025148.
• 8. Obas V, Vasan RS. The aging heart. Clinical Science. 2018;132(13):1367-82.
• 9. Hansen M, Rubinsztein DC. Autophagy as a promoter of longevity: insights from model organisms. Nature Reviews. Molecular Cell Biology . 2018;19(9):579-93.
• 10. Wang S, Ge W, Harns C, et al. Ablation of toll-like receptor 4 attenuates aging-induced myocardial remodeling and contractile dysfunction through NCoRI-HDAC1-mediated regulation of autophagy. Journal of Molecular and Cellular Cardiology. 2018;119:40-50.
• 11. Bravo-San Pedro JM, Kroemer G, Galluzzi L. Autophagy and Mitophagy in Cardiovascular Disease. Circulation Research. 2017;120(11):1812-24.
• 12. Gao G, Chen W, Yan M, et al. Rapamycin regulates the balance between cardiomyocyte apoptosis and autophagy in chronic heart failure by inhibiting mTOR signaling. International Journal of Molecular Medicine. 2020;45(1):195-209.
• 13. Küçüköner M. mTOR Signaling Pathway and mTOR inhibitors in the treatment of Cancer. Dicle Medicine Journal. 2013; 40(1): 156-160.
• 14. Lin S, Wang Y, Zhang X, t al. HSP27 Alleviates Cardiac Aging in Mice via a Mechanism Involving Antioxidation and Mitophagy Activation. Oxidative Medicine and Cellular Longevity. 2016;2016:2586706.
• 15. Qi J, Luo X, Ma Z, et al. Downregulation of miR-26b-5p, miR-204-5p, and miR-497-3p Expression Facilitates Exercise-Induced Physiological Cardiac Hypertrophy by Augmenting Autophagy in Rats. Frontiers in Genetics. 2020;11:78.
• 16. Kang R, Li R, Dai P, et al. Deoxynivalenol induced apoptosis and inflammation of IPEC-J2 cells by promoting ROS production. Environmental Pollution (Barking, Essex : 1987). 2019;251:689-98.
• 17. Ochoa CD, Wu RF, Terada LS. ROS signaling and ER stress in cardiovascular disease. Molecular aspects of Medicine. 2018;63:18-29.
• 18. Wray DW, Amann M, Richardson RS. Peripheral vascular function, oxygen delivery and utilization: the impact of oxidative stress in aging and heart failure with reduced ejection fraction. Heart Failure Reviews. 2017;22(2):149-66.
• 19. Forte M, Nocella C, De Falco E, et al. The Pathophysiological Role of NOX2 in Hypertension and Organ Damage. High Blood Press Cardiovasc Prev. 2016;23(4):355-64.
• 20. Lyu G, Guan Y. TGF-β signaling alters H4K20me3 status via miR-29 and contributes to cellular senescence and cardiac aging. Nature Communications. 2018;9(1):2560.
• 21. Guo W, Liu X, Li J, et al. Prdx1 alleviates cardiomyocyte apoptosis through ROS-activated MAPK pathway during myocardial ischemia/reperfusion injury. International Journal of Biological Macromolecules. 2018;112:608-15.
• 22. Van der Bliek AM, Sedensky MM. Cell Biology of the Mitochondrion. Genetics. 2017;207(3):843-71.
• 23. Konradi J, Mollenhauer M, Baldus S, et al. Redox-sensitive mechanisms underlying vascular dysfunction in heart failure. Free Radical Research. 2015;49(6):721-42.
• 24. Yan C, Duanmu X, Zeng L, et al. Mitochondrial DNA: Distribution, Mutations, and Elimination. Cells. 2019;8(4).
• 25. Chistiakov DA, Shkurat TP, Melnichenko AA, et al. The role of mitochondrial dysfunction in cardiovascular disease: a brief review. Annals of Medicine. 2018;50(2):121-7.
• 26. Ye J, Wang Y, Wang Z, et al. Interleukin-12p35 deficiency enhances mitochondrial dysfunction and aggravates cardiac remodeling in aging mice. Aging (Albany NY). 2020;12(1):193-203.
• 27. Turner KJ, Vasu V, Griffin DK. Telomere Biology and Human Phenotype. Cells. 2019;8(1):73.
• 28. Yeh J-K, Wang C-Y. Telomeres and Telomerase in Cardiovascular Diseases. Genes (Basel). 2016;7(9):58.
• 29. Ellehoj H, Bendix L, Osler M. Leucocyte Telomere Length and Risk of Cardiovascular Disease in a Cohort of 1,397 Danish Men and Women. Cardiology. 2016;133(3):173-7.
• 30. Zhan Y, Hägg S. Telomere length and cardiovascular disease risk. Current Opinion in Cardiology. 2019;34(3):270-4.
• 31. Wang Q, Yu X, Dou L, et al. miR-154-5p Functions as an Important Regulator of Angiotensin II-Mediated Heart Remodeling. Oxidative Medicine and Cellular Longevity. 2019;8768164.
• 32. Kinser HE, Pincus Z. MicroRNAs as modulators of longevity and the aging process. human Genetics. 2020;139(3):291-308.
• 33. Lozano-Vidal N, Bink DI, Boon RA. Long noncoding RNA in cardiac aging and disease. Journal of Molecular Cell Biology. 2019;11(10):860-7.
• 34. Micheletti R, Plaisance I, Abraham BJ. The long noncoding RNA Wisper controls cardiac fibrosis and remodeling. Science Translational Medicine. 2017;9(395).
• 35. Cordero MD, Williams MR, Ryffel B. AMP-Activated Protein Kinase Regulation of the NLRP3 Inflammasome during Aging. Trends in endocrinology and metabolism: TEM. 2018;29(1):8-17.
• 36. Gao G, Chen W, Yan M, et al. Rapamycin regulates the balance between cardiomyocyte apoptosis and autophagy in chronic heart failure by inhibiting mTOR signaling. International Journal of Molecular Medicine. 2020;45(1):195-209.
• 37. Masui K, Harachi M, Cavenee WK, et al. mTOR complex 2 is an integrator of cancer metabolism and epigenetics. Cancer Letters. 2020;478:1-7.
• 38. He Y, Zuo C, Jia D, et al. Loss of DP1 Aggravates Vascular Remodeling in Pulmonary Arterial Hypertension via mTORC1 Signaling. American Journal of Respiratory and Critical Care Medicine. 2020;201(10):1263-76.
• 39. Marín-Aguilar F, Lechuga-Vieco AV, Alcocer-Gómez E, et al. NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice. Aging Cell. 2020;19(1):e13050.
• 40. Lee WS, Kim J. Insulin-like growth factor-1 signaling in cardiac aging. Biochimica et Biophysica Acta Molecular Basis of Disease. 2018;1864(5 Pt B):1931-8.
• 41. Van der Spoel E, Rozing MP, Houwing-Duistermaat JJ, et al. Association analysis of insulin-like growth factor-1 axis parameters with survival and functional status in nonagenarians of the Leiden Longevity Study. Aging (Albany NY). 2015;7(11):956-63.
• 42. Kismiroğlu C, Cengiz S, Yaman M. Biochemistry of AMPK: Mechanisms of Action and Its Importance in the Treatment of Diabetes. European Journal of Science and Technology. 2020(18):162-70.
• 43. Jiang S, Li T, Yang Z, et al. AMPK orchestrates an elaborate cascade protecting tissue from fibrosis and aging. Ageing Research Reviews. 2017;38:18-27.
• 44. Smith SC, Zhang X, Zhang X, et al. GDF11 does not rescue aging-related pathological hypertrophy. Circulation Research. 2015;117(11):926-32.
• 45. Poggioli T, Vujic A, Yang P, et al. Circulating growth differentiation factor 11/8 levels decline with age. Circulation research. 2016;118(1):29-37.
• 46. Akdeniz M, Kavukcu E, Teksan A. Physiological Changes Related to Aging and Their Reflections to the Clinic. Turkiye Klinikleri. 2019;10(3):1-15.
• 47. Singam NSV, Fine C, Fleg JL. Cardiac changes associated with vascular aging. Clinical Cardiology. 2020;43(2):92-8.
• 48. Tracy E, Rowe G, LeBlanc AJ. Cardiac tissue remodeling in healthy aging: the road to pathology. American Journal of Physiology-Cell Physiology. 2020;319(1):C166-C82.
• 49. Sun Z. Aging, arterial stiffness, and hypertension. Hypertension. 2015;65(2):252-6.
• 50. Nkomo VT, Gardin JM, Skelton TN, et al. Burden of valvular heart diseases: a population-based study. Lancet. 2006;368(9540):1005-1011.
• 51. Yeşilbursa D. Yaşlılarda mitral kapak hastalıklarına yaklaşım [Approach to mitral valve diseases in the elderly]. Turk Kardiyol Dern Ars. 2017;45(Suppl 5):52-55.
• 52. Abramowitz Y, Jilaihawi H, Chakravarty T, et al. Mitral Annulus Calcification. J Am Coll Cardiol. 2015;66(17):1934-1941.
• 53. Pascale A, Govoni S. Cerebral aging: implications for the heart autonomic nervous system regulation. Heart Failure Management: The Neural Pathways: Springer; 2016. p.115-27.
• 54. Parashar R, Amir M, Pakhare A, et al. Age related changes in autonomic functions. Journal of clinical and diagnostic research: JCDR. 2016;10(3):CC11.
• 55. Ferrara N, Komici K, Corbi G, et al. β-adrenergic receptor responsiveness in aging heart and clinical implications. Front Physiol. 2014;4:396.
• 56. Lymperopoulos A, Rengo G, Koch WJ. Adrenergic nervous system in heart failure: pathophysiology and therapy [published correction appears in Circ Res. 2016 Aug 5;119(4):e38]. Circ Res. 2013;113(6):739-753.
• 57. Credeur DP, Holwerda SW, Boyle LJ, et al. Effect of aging on carotid baroreflex control of blood pressure and leg vascular conductance in women. Am J Physiol Heart Circ Physiol. 2014;306(10):H1417-H1425.
• 58. Sharpe EJ, Larson ED, Proenza C. Cyclic AMP reverses the effects of aging on pacemaker activity and If in sinoatrial node myocytes. J Gen Physiol. 2017;149(2):237-247.
• 59. Murphy C, Lazzara R. Current concepts of anatomy and electrophysiology of the sinus node. Journal of Interventional Cardiac Electrophysiology. 2016;46(1):9-18.