Yaşlanma Teorileri ve Tedavi Yaklaşımları

Yaşlanma kronolojik, psikolojik, toplumsal ve biyolojik yönleri olan kaçınılmaz bir süreçtir. Fizyolojik kapasitedeki ilerleyici azalma ve çevresel streslere cevap verme yeteneğinde azalma, hastalıklara karşı artmış duyarlılık ve hassasiyete yol açmaktadır. Sonuçta, tüm bu nedenlere bağlı olarak yaşlanmayla birlikte mortalite artmaktadır. Geçmişte birçok insan genç yaşta ölürken, 20. yüzyıldaki gelişmeler sonrasında insanlarda daha uzun yaşama fikri oluşmuş, ‘anti-yaşlanma' daha ilgi çeken bir konu haline gelmiş ve yaşlanmanın nedenleri ortaya koymak, yaşlanmayı tedavi etmek ya da belirtilerini azaltmak için çeşitli çalışmalar yapılmıştır. Bu derlemede, yaşlanmanın mekanizmalarını açıklayan teoriler ve muhtemel tedavi yaklaşımları tartışılmaktadır.

Aging Theories and Treatment Approaches

Aging is an inevitable process that have chronological, psychological, social and biological aspects. The progressive decrease in physiological capacity and the reduced ability to respond to environmental stresses lead to increased susceptibility and vulnerability to diseases. Consequently, mortality due to all these causes increases with aging. While many people died at young ages in the past, after the developments in 20th century, people have developed the idea of living longer, 'antiaging' has become a subject of interest and various studies have been done to reveal the causes of aging, to treat aging or to reduce the symptoms of aging. İn this review, theories explaining the mechanisms of aging and potential therapeutic approaches are discussed.

___

  • Atlı K, Bozcuk AN.: Telomer ve Hücresel Yaşlanma. Turkish Journal of Geriatrics 2002;5(3):111-114.
  • Blasco MA.: Telomere length, stem cells anda aging. Nature Chemical Biology 2007;3(10):640-649.
  • Blagosklonny MV.: An anti- aging drug today: from senescence- promoting genes to anti-aging pill. Drug Discovery Today 2007;12(5/6):218-224.
  • Blagosklonny MV.: Revisiting the antagonistic pleiot- rophy theory of aging TOR-driven program and qua- si-program. Cell Cycle 2010; 9(16):3151-3156.
  • Gül S, Çetin M, Evrenkaya R, Danacı M, Küçükardalı Y.: Yaşlılık, Yaşlanmanın Biyolojisi ve Psikolojisi. T Klin Tıp Bilimleri 1993;13:238-248.
  • Zengin G,Başak T.: Deri Yaşlanması. T Klin Tıp Bilimle- ri 1991;11:506-510.
  • Dönderici L, Taşpınar A.: Deri Yaşlanması. Turk J Der- matol 1994;4: 56-61.
  • Blagosklonny MV.: Validation of anti-aging drugs by treating age-related diseases. Aging 2009;1(3): 281- 288.
  • Heilbronn LK, Ravussin E.: Calorie restriction and aging: review of the literature and implications for studies in humans. Am J Clin Nutr 2003;78:361-369.
  • Holloszy JO, Fontana L.: Caloric restriction in humans. Exp Gerontol 2007; 42(8):709-712.
  • Kennedy BK, Steffen KK, Kaeberlein M.: Ruminations on dietary restriction and aging. Cell Mol. Life Sci. 2007;64:1323-1328.
  • Anisimov VN. Metformin for aging and cancer pre- vention. Aging 2010; 2(11):760-774.
  • Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA et al.: Effect of metfor- min on life span and on the development of sponta- neous mammary tumors in HER-2/neu transgenic mi- ce. Exp. Gerontol 2005;40:685-693.
  • Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA et al.: Metformin slows down aging and extends life span of female SHR mi- ce. Cell Cycle 2008; 7(17):2769-2773.
  • Buzzai M, Jones RG, Amaravadi RK, Lum JJ, DeBerar- dinis RJ, Zhao F et al.: Systemic treatment with the an- tidiabetic drug metformin selectively impairs p53-de- ficient tumor cell growth. Cancer Res 2007;67(14): 6745-6752.
  • Evans JMM, Donnely LA, Emslie-Smith AM, Alessi DR, Morris AD.: Metformin and reduced risk of cancer in diabetic patients. BMJ 2005;330:1304-1305.
  • Libby G, Donnely LA, Donan PT, Alessi DR, Morris AD, Evans JMM.: New users of metformin are at low risk of incident cancer. Diabetes Care 2009; 32(9):1620- 1625.
  • Sahra IB, Marchand-Brustel YLM, Tanti JF, Bost F.: Metformin in cancer therapy: a new perspective for an old antidiabetic drug? Mol Cancer Ther 2010; 9(5):1092-1099.
  • Sirtori CR, Catapano A, Ghiselli GC, İnnocenti AL, Rodriguez J.: Metformin:an antiatherosclerotic agent modifying very low density lipoproteins in rabbits. At- herosclerosis 1977;26:79-89.
  • Mamputu JC, Wiernsperger NF, Renier G.: Antiathe- rogenic properties of metformin: the experimental evidence. Diabetes Metab 2003; 29:6571-6576.
  • Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Fo- ley A et al.: Mechanisms of life span extension by ra- pamycin in the fruit fly Drosophila melanogaster. Cell Metab 2010; 11(1):35-46.
  • Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, et al. Rapamycin fed late in life extends li- fespan in genetically heterogeneous mice. Nature 2009;460 (7253):392-395.
  • Anisimov VN, Zabezhinski MA, Popovich IG, Piskuno- va TS, Semenchenko AV, Tyndyk ML, et al.: Rapamy- cin extends maximal lifespan in cancer-prone mice. Am J Pathol 2010;176(5):2092-2097.
  • Law B.K.: Rapamycin:an anti-cancer immunosuppres- sant? Crit. Rev. Oncol. Hematol.2005; 56:47–60.
  • Romero D.F, et al.: Rapamycin: a bone sparing immu- nosuppressant? J. Bone Miner. Res 1995;10: 760– 768.
  • Mohsin N. et al.: Complete regression of visceral Ka- posi’s sarcoma after conversion to sirolimus. Exp. Clin. Transplant 2005;3:366–369.
  • Rizell M. et al.: Impressive regression of primary liver cancer after treatment with sirolimus. Acta Oncol. 2005;44:496.
  • Pakala R, Stabile E, Jang GJ, Clavijo L, Waksman R.: Rapamycin attenuates atherosclerotic plaque progres- sion in apolipoprotein E knockout mice: inhibitory ef- fect on monocyte chemotaxis. J Cardiovasc Pharma- col 2005;46:481-486.
  • Spilman P, Podlutskaya N, Hart MJ, Debnath J, Goros- tiza O, Bredesen D et al.: Inhibition of mTOR by ra- pamycin abolishes cognitive deficits and reduces amy- loid-b levels in a mouse model of Alzheimer’s disease. www.plosone.org 2010;5(4):e9979. doi:10.1371/jo- urnal.pone.0009979
  • Malagelada C, Jin ZH, Jackson-Lewis V, Przedborski S, Greene LA. Rapamycin protects against neuron de- ath in In vitro and In vivo models of Parkinson’s disea- se. The Journal of Neuroscience 2010; 30(3):1166 –1175.
  • Howitz, K.T, Bitterman KJ, Cohen HY, Lamming DW, Lavu S,Wood JG et al.: Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Na- ture 2003; 425:191–196.
  • Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A et al.: Resveratrol improves health and survi- val of mice on a high calorie diet. Nature 2006; 444, 337–342.
  • Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shiahodia S, Takada Y.:Role of resveratrol in preventi- on and therapy of cancer: preclinical and clinical stu- dies. Anticancer research 2004; 24:2783-2840 .
  • Bradamante S, Barenghi L, Villa A.: Cardiovascular Protective Effects of Resveratrol. Cardiovascular Drug Reviews 2004;22(3): 169–188.
  • Sun AY, Wang Q, Simonyi A, Sun GY.: Resveratrol as a therapeutic agent for neurodegenerative diseases. Mol Neurobiol. 2010; 41(2-3):375–383.
  • Ünlühızarcı K.: Yaşlanma sürecinde büyüme hormo- nu:antiaging’de terapötik potansiyeli. Türkiye Klinikle- ri J Med Sci 2008;28(suppl): S79-S81.
  • Khansari DN, Gustad T.: Effects of long-term, low-do- se growth hormone therapy on immune function and life expectancy of mice. Mech Aging Dev 1991;57(1): 87-100.
  • Liu H, Bravata DM, Olkin I, et al.: Systematic review: the safety and efficacy of growth hormone in the he- althy elderly. Ann Intern Med 2007;146(2):104-115.
  • Mollaoğlu H, Özgüner MF.: Yaşlanma sürecinde me- latoninin rolü. S.D.Ü Tıp. Fak. Derg. 2005;12(3):52- 56.
  • Wang X.: The antiapoptotic activity of melatonin in neurodegenerative diseases.CNS Neurosci. Ther. 2009;15(4): 345–357.
  • Kedziora-Kornatowska K., Szewczyk-Golec K, Czuc- zejko J, et al.: Antioxidative effects of melatonin ad- ministration in elderly primary essential hypertension patients. J. Pineal Res 2008; 45(3):312–317.
  • Kedziora-Kornatowska K, Szewczyk-Golec K, Koza- kiewicz, et al. Melatonin improves oxidative stress pa- rameters measured in the blood of elderly type 2 di- abetic patients. J. Pineal Res. 2009;46(3):333–337.
  • Dominguez-Rodriguez A, Abreu-Gonzalez P, Reiter RJ..: Clinical aspects of melatonin in the acute coro- nary syndrome. Curr. Vasc. Pharmacol. 2009; 7(3): 367–373.
  • Anisimov VN, Popovich IG, Zabezhinski MA, Anisimov SV, Vesnushkin GM, Vinogradova IA.: Melatonin as antioxidant, geroprotector and anticarcinogen. Bioc- him. Biophys. Acta 2006;1757(5-6): 573–589.
  • Howes RM.: The free radical fantasy: a panoply of pa- radoxes. Ann N. Y. Acad. Sci. 2006; 1067:22-26
  • de Jesus BB, Schneeberger K, Vera E, Tejera A, Harley CB, Blasco MA.: The telomerase activator TA-65 elon- gates short telomeres and increases health span of adult old mice without increasing cancer incidence. Aging Cell 2011;10(4):604-621.
  • Yamamoto M, Clark JD, Pastor JV, et al.: Regulation of oxidative stress by the anti-aging hormone klotho. The Journal of Bıologıcal Chemıstry 2005; 280(45):38029–38034.
  • Arking DE, Krebsova A, Macek M Sr, et al.: Associati- on of human aging with a functional variant of klot- ho. Proc Natl Acad Sci U S A 2002;99(2):856-861.
Maltepe Tıp Dergisi-Cover
  • Yayın Aralığı: Yılda 3 Sayı
  • Başlangıç: 2009
  • Yayıncı: Maltepe Üniversitesi