Senescence Model Theories from In Vitro through In Vivo

Abstract

The theoretical equivalence of expressing that a cell is aging to its inability to perform the assumed function is not exactly accurate, it involves a gradual decrease in cell aging mechanisms. Factors such as genetics, lifestyle, and environmental effects maintain the biological change of the cell. The concept of cellular senescence was initially introduced by Hayflick and his collaborators in 1961 when they noticed that human diploid fibroblasts cultured in vitro could undergo only a limited number of cell divisions before their ability to proliferate was permanently halted. This phenomenon, known as the 'Hayflick limit', was subsequently linked to the gradual shortening of telomeres with each successive round of cell division. Throughout the aging process, senescent cells collect in different tissues. Their involvement in age-related health issues such as neurodegenerative disorders, heart problems, cancer, kidney-related changes, chronic lung diseases, and osteoarthritis suggests that targeting senescent cells therapeutically could be promising across various health conditions. This review will discuss the available data on which cell types may undergo aging based on biological aging and how these processes may impact age-associated tissue-specific pathologies. Additionally, the markers used to characterize the physiological transition of aging cells from in vitro to in vivo settings will be evaluated. The discussed data may serve as a significant starting point for an expanded definition of the molecular and functional characteristics of aging cells in different organs, thus supporting the development and enhancement of targeting strategies in vivo.

Keywords

• Cell senescence
• geriatric in vivo models
• cellular aging theories
• biological aging mechanism

In Vitro’dan In Vivo’ya Yaşlılık Model Teorileri

Abstract

Bir hücrenin, varsayılan işlevini yerine getiremeyecek kadar yaşlanmasının karşılığı hücrenin biyolojik süreçlerinde her zaman tam bir yetersizliğe yol açmayabilir, hücre yaşlanma mekanizmalarında kademeli bir azalmayı içerir. Hücrenin biyolojik değişimini genetik, yaşam tarzı ve çevresel etkiler gibi faktörler sürdürür. Hücresel yaşlanma kavramı ilk olarak 1961 yılında Hayflick ve çalışma arkadaşları tarafından, in vitro kültüre alınan insan diploid fibroblastlarının çoğalma yetenekleri kalıcı olarak durdurulmadan önce yalnızca sınırlı sayıda hücre bölünmesine maruz kalabileceğini fark ettiklerinde ortaya atıldı. 'Hayflick sınırı' olarak bilinen bu fenomen, daha sonra, birbirini izleyen her hücre bölünmesi turunda telomerlerin kademeli olarak kısalması ile ilişkilendirildi. Yaşlanma süreci boyunca yaşlanan hücreler farklı dokularda toplanmaktadır. Nörodejeneratif ve kardiyovasküler bozukluklar, kanser, böbrekle ilgili değişiklikler, kronik akciğer hastalıkları ve osteoartrit gibi yaşa bağlı sağlık sorunlarına katılımları, yaşlanan hücreleri terapötik olarak hedeflemenin çeşitli sağlık koşullarında umut verici olabileceğini düşündürmektedir. Bu derlemede biyolojik yaşlanmaya bağlı olarak hangi hücre tiplerinin yaşlanabileceğine ve bu süreçlerin yaşla ilişkili dokuya özgü patolojileri nasıl etkileyebileceğine dair mevcut veriler tartışılacaktır. Ek olarak, yaşlanan hücrelerin in vitro ortamdan in vivo ortama fizyolojik geçişini karakterize etmek için kullanılan belirteçler de değerlendirilecektir. Tartışılan veriler, farklı organlarda yaşlanan hücrelerin moleküler ve fonksiyonel özelliklerinin genişletilmiş bir tanımı için önemli bir başlangıç noktası olarak hizmet edebilir, böylece in vivo hedefleme stratejilerinin geliştirilmesini ve artırılmasını destekleyebilir.

Keywords

• Hücre yaşlanması
• geriatrik in vivo modeller
• hücresel yaşlanma teorileri
• biyolojik yaşlanma mekanizması

References

1. Zheng Z. Twenty years’ follow-up on elder people’s health and quality of life. China Popul Dev Stud. 2020;3(4):297-309.
2. Adana F, Durmaz S, Özvurmaz S, Akpınar CV, Yeşilfidan D. Descriptors of living alone for elders: based on Turkey national data. BMC Geriatr. 2022;22(1):37.
3. Hayflick L. Theories of biological aging. Exp Gerontol. 1985;20(3-4):145-59.
4. Ersözlü M, Aydemir MA. Permanent, continuous and interested: ageless older adults. Senex: J Aging Stud. 2021;5(1):19-46. Turkish.
5. Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res. 1965;37:614-36.
6. Di Micco R, Krizhanovsky V, Baker D, d'Adda di Fagagna F. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat Rev Mol Cell Biol. 2021;22(2):75-95.
7. Zhang L, Pitcher LE, Yousefzadeh MJ, Niedernhofer LJ, Robbins PD, Zhu Y. Cellular senescence: a key therapeutic target in aging and diseases. J Clin Invest. 2022;132(15):e158450.
8. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-217.

9. Mahmoudi S, Brunet A. Aging and reprogramming: a two-way street. Curr Opin Cell Biol. 2012;24(6):744-56.
10. Rattan SIS. If aging is a disease, then it is your own fault. J Aging Sci. 2016;4(2):e120.
11. Sikora E, Bielak-Żmijewska A, Mosieniak G. What is and what is not cell senescence. Postepy Biochem. 2018;64(2):110-8.
12. Razgonova MP, Zakharenko AM, Golokhvast KS, Thanasoula M, Sarandi E, Nikolouzakis K, et al. Telomerase and telomeres in aging theory and chronographic aging theory (Review). Mol Med Rep. 2020;22(3):1679-94.
13. Slijepcevic P. DNA damage response, telomere maintenance and ageing in light of the integrative model. Mech Ageing Dev. 2008;129(1-2):11-6.
14. Schumacher B, Pothof J, Vijg J, Hoeijmakers JHJ. The central role of DNA damage in the ageing process. Nature. 2021;592(7856):695-703.
15. Stead ER, Bjedov I. Balancing DNA repair to prevent ageing and cancer. Exp Cell Res. 2021;405(2):112679.
16. Clarke TL, Mostoslavsky R. DNA repair as a shared hallmark in cancer and ageing. Mol Oncol. 2022;16(18):3352-79.
17. Petr MA, Tulika T, Carmona-Marin LM, Scheibye-Knudsen M. Protecting the aging genome. Trends Cell Biol. 2020;30(2):117-32.
18. Mc Auley MT, Guimera AM, Hodgson D, Mcdonald N, Mooney KM, Morgan AE, et al. Modelling the molecular mechanisms of aging. Biosci Rep. 2017;37(1):BSR20160177.
19. Vilchez D, Saez I, Dillin A. The role of protein clearance mechanisms in organismal ageing and age-related diseases. Nat Commun. 2014;5:5659.
20. Wolf AM. MtDNA mutations and aging-not a closed case after all? Signal Transduct Target Ther. 2021;6(1):56.
21. Sendama W. The effect of ageing on the resolution of inflammation. Ageing Res Rev. 2020;57:101000.
22. Pansarasa O, Mimmi MC, Davin A, Giannini M, Guaita A, Cereda C. Inflammation and cell-to-cell communication, two related aspects in frailty. Immun Ageing. 2022;19(1):49.
23. Wanner E, Thoppil H, Riabowol K. Senescence and apoptosis: architects of mammalian development. Front Cell Dev Biol. 2021;8:620089.
24. Hu L, Li H, Zi M, Li W, Liu J, Yang Y, et al. Why senescent cells are resistant to apoptosis: an insight for senolytic development. Front Cell Dev Biol. 2022;10:822816.
25. Kumar A, Bano D, Ehninger D. Cellular senescence in vivo: From cells to tissues to pathologies. Mech Ageing Dev. 2020;190:111308.
26. Ocampo A, Reddy P, Martinez-Redondo P, Platero-Luengo A, Hatanaka F, Hishida T, et al. In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell. 2016;167(7):1719-33.e12.
27. Rabinowitz ZM, Cui L. Detecting cellular senescence in vivo: Imagining imaging better. Aging Cancer. 2023;4(3-4):97-110.
28. Mack HID, Heimbucher T, Murphy CT. The nematode Caenorhabditis elegans as a model for aging research. Drug Discov Today Dis Models. 2018;27:3-13.
29. Alpatov WW, Pearl R. Experimental studies on the duration of life. XII. influence of temperature during the larval period and adult life on the duration of the life of the imago of Drosophila melanogaster. Am Nat. 1929;63(684):37-67.
30. Conti B. Considerations on temperature, longevity and aging. Cell Mol Life Sci. 2008;65(11):1626-30.
31. Veronesi F, Contartese D, Di Sarno L, Borsari V, Fini M, Giavaresi G. In vitro models of cell senescence: a systematic review on musculoskeletal tissues and cells. Int J Mol Sci. 2023;24(21):15617.
32. Hartmann C, Herling L, Hartmann A, Köckritz V, Fuellen G, Walter M, et al. Systematic estimation of biological age of in vitro cell culture systems by an age-associated marker panel. Front Aging. 2023;4:1129107.
33. Minteer C, Morselli M, Meer M, Cao J, Higgins-Chen A, Lang SM, et al. Tick tock, tick tock: Mouse culture and tissue aging captured by an epigenetic clock. Aging Cell. 2022;21(2):e13553.
34. Brunet A. Old and new models for the study of human ageing. Nat Rev Mol Cell Biol. 2020;21(9):491-3.
35. Browder KC, Reddy P, Yamamoto M, Haghani A, Guillen IG, Sahu S, et al. In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice. Nat Aging. 2022;2(3):243-53.
36. Folgueras AR, Freitas-Rodríguez S, Velasco G, López-Otín C. Mouse models to disentangle the hallmarks of human aging. Circ Res. 2018;123(7):905-24.
37. Mitchell SJ, Scheibye-Knudsen M, Longo DL, de Cabo R. Animal models of aging research: implications for human aging and age-related diseases. Annu Rev Anim Biosci. 2015;3:283-303.
38. Yu Y, Lu C, Yu W, Lei Y, Sun S, Liu P, et al. B cells dynamic in aging and the implications of nutritional regulation. Nutrients. 2024;16(4):487.
39. Liu RK, Walford RL. The effect of lowered body temperature on lifespan and immune and non-immune processes. Gerontologia. 1972;18(5-6):363-88.