Cellular senescence as a quality parameter in chronological aging

Said Rodea, Eduvigis Solórzano N.

Resumen


DOI: https://doi.org/10.53766/AcBio/2023.13.26.13

Chronological aging and its difference with biological aging have been the subject of study for many years, trying to define within biological aging the causes or pathways by which this process of homeostatic deterioration occurs. Until the beginning of this year, 13 "Hallmarks of aging" have been defined, which describe the aging process from a molecular, cellular and systemic point of view, which are DNA instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, disabled macroautophagy, chronic inflammation, and dysbiosis. When conducting research on each of them, our attention was drawn to the close relationship between all of them and cellular senescence as a result of most of these processes. Cellular senescence refers to an irreversible form of long-term arrest of the cell cycle, which causes a loss of the ability to participate in tissue repair, in addition to damage caused through the secretion of senescence-associated secretory phenotype (SASP), which is closely linked to all known processes of biological aging. In this article we describe what cellular senescence is, what are the different processes or "Hallmarks" of aging currently defined, and their close relationship with cellular senescence. In addition, we took different approach to senescence to use it as a quality metric in chronological aging, instead of using it to define a biological age as it has been approached in the past.

Recibido: 14/07/2023
Aceptado: 1/09/2023

 

Palabras clave


Cellular senescence; Biomarkers; Cellular aging; Inmunosenescence

Texto completo:

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Referencias


Strehler BL, ed. Understanding aging. In: Barnett YA, Barnett CR, eds. Aging Methods and Protocols. Methods in Molecular Medicine. Totowa: Humana

Press Inc; (2000). p. 1-19. https://doi.org/10.1385/1-59259-070-5:1

Hamczyk et al. Biological Versus Chronological Vascular Aging. JACC (2020) VOL. 75, NO. 8: 919–30. https://doi.org/10.1016/j.jacc.2019.11.062

Morgan E. Levine et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (2018), Vol.10, No.4

Z. Wang (ed.), Aging and Aging-Related Diseases, Advances in Experimental Medicine and Biology 1086, Springer Nature Singapore Pte Ltd.

(2018), https://doi.org/10.1007/978-981-13-1117-8_14

López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. (2013); 153:1194–217. https://doi.org/10.1016/j.cell.2013.05.039 PMID:23746838

Lopez-Otin C et al. Hallmarks of aging: An expanding Universe. Cell (January 19, 2023). 186; 243-278

McHugh D, Gil J. Senescence and aging: Causes, consequences, and therapeutic avenues. J Cell Biol. (2018); 217: 65-77. https://doi.org/10.1083/jcb.201708092

Hernández R, Fernández C, Baptista P, Hernandez Sampieri R, Fernandez Collado C, Baptista Lucio M del P. Definición del tipo de investigación a

realizar: básicamente exploratoria, descriptiva, correlacional o explicativa [Internet]. Metodología de la investigación. (1991). 57–73 p. Available

from: http://www.casadellibro.com/librometodologia-de-la-investigacion-5-edincluye-cdrom/9786071502919/1960006%5Cnhttp://sapp.uv.mx/univirtual/especialidadesmedicas/mi2/modulo1/docs/Met_Invest_a.pdf

Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D, et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and

Explanation. Ann Intern Med [Internet]. 2018 Oct 2;169(7):467–73. Available from: http://www.elsevier.com/locate/scp

Peters M, C G, P M, Z M, AC T, Khalil H. 2017 Guidance for the Conduct of JBI Scoping Reviews Chapter 11 : Scoping Reviews Scoping Reviews. Underst

scoping Rev Defin Purp Process. 2017;(September).

Noren Hooten N, Evans MK. Techniques to induce and quantify cellular senescence. J Vis Exp. (2017); 123. 10.3791/55533. https://doi.org/10.3791/55533

Campisi, J. Aging, cellular senescence, and cancer. Annu. Rev. Physiol. (2013). 75, 685–705 13 Munoz-Espin, D. & Serrano, M. Cellular senescence: from physiology to pathology. Nat. Rev. Mol. Cell Biol. (2014). 15, 482–496 14 Van Deursen, J. M. The role of senescent cells in ageing. Nature (2014).

, 439–446

Munoz-Espin, D. & Serrano, M. Cellular senescence: from physiology to pathology. Nat. Rev. Mol. Cell Biol. (2014). 15, 482–496

Van Deursen, J. M. The role of senescent cells in ageing. Nature (2014). 509, 439–446

Baker, D. J. et al. Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature (2016). 530, 184–189 16 Faget, D.V., Ren, Q., and Stewart, S.A. Unmasking senescence: contextdependent effects of SASP in cancer. Nat. Rev. Cancer (2019). 19, 439–453. https://doi.org/10.1038/s41568-019-0156-2.

Faget, D.V., Ren, Q., and Stewart, S.A. Unmasking senescence: contextdependent effects of SASP in cancer. Nat. Rev. Cancer (2019). 19, 439–453.

https://doi.org/10.1038/s41568-019-0156-2.

Niedernhofer LJ, Gurkar AU, Wang Y, Vijg J, Hoeijmakers JHJ and Robbins PD “Nuclear Genomic Instability and Aging.” Annu Rev Biochem (2018). 87:

–322. [PubMed: 29925262]

Blokzijl, F., de Ligt, J., Jager, M.,Sasselli, V., Roerink, S., Sasaki, N., Huch, M., Boymans, S., Kuijk, E., Prins, P., et al. Tissue-specific mutation accumulation in human adult stem cells during life. Nature (2016). 538, 260–264. https://doi.org/10.1038/nature19768 19 Nik-Zainal, S., and Hall, B.A. Cellular survival over genomic perfection. Science (2019). 366, 802–803. https://doi.org/10.1126/science. aax8046. 20 Blackburn, E.H., Epel, E.S., and Lin, J. Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection. Science (2015). 350, 1193–1198.

https://doi.org/10.1126/science.aab3389.

Nik-Zainal, S., and Hall, B.A. Cellular survival over genomic perfection. Science (2019). 366, 802–803. https://doi.org/10.1126/science. aax8046.

Blackburn, E.H., Epel, E.S., and Lin, J. Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection. Science (2015). 350, 1193–1198. https://doi.org/10.1126/science.aab3389.

Rossiello, F., Jurk, D., Passos, J.F., and d’Adda di Fagagna, F. Telomere dysfunction in ageing and age-related diseases. Nat. Cell Biol. (2022). 24, 135–147. https://doi.org/10.1038/s41556-022-00842-x.

Sen P, Shah PP, Nativio R and Berger SL “Epigenetic Mechanisms of Longevity and Aging.” Cell (2016). 166(4): 822– 839. [PubMed: 27518561]

Wang, W., Zheng, Y., Sun, S., Li, W., Song, M., Ji, Q., Wu, Z., Liu, Z., Fan, Y., Liu, F., et al. A genome-wide CRISPRbased screen identifies KAT7 as a driver of cellular senescence. Sci. Transl. Med. (2021). 13, eabd2655. https://doi.org/10.1126/scitranslmed.abd2655.

Gorbunova, V., Seluanov, A., Mita, P., McKerrow, W., Fenyo ¨ , D., Boeke, J.D., Linker, S.B., Gage, F.H., Kreiling, J.A., Petrashen, A.P., et al. The role of retrotransposable elements in ageing and age-associated diseases. Nature (2021). 596, 43–53. https://doi.org/10.1038/s41586-021-03542-y

Della Valle, F., Reddy, P., Yamamoto, M., Liu, P., Saera-Vila, A., Bensad- dek, D., Zhang, H., Prieto Martinez, J., Abassi, L., Celii, M., et al. LINE-1 RNA causes heterochromatin erosion and is a target for amelioration of senescent phenotypes in progeroid syndromes. Sci. Transl. Med.

(2022). 14, eabl6057. https://doi.org/10.1126/scitranslmed.abl6057.

Hipp MS, Kasturi P and Hartl FU “The proteostasis network and its decline in ageing.” Nat Rev Mol Cell Biol (2019). 20(7): 421–435. [PubMed: 30733602]

Kaushik S and Cuervo AM “Proteostasis and aging.” Nat Med (2015). 21(12): 1406–1415. [PubMed: 26646497]

Levine, B., and Kroemer, G. Biological functions of autophagy genes: a disease perspective. Cell (2019). 176, 11–42. https://doi.org/10.1016/

j.cell.2018.09.048.

Wong SQ, Kumar AV, Mills J, Lapierre LR. Autophagy in aging and longevity. Hum Genet. (2020); 139:277–90. https://doi.org/10.1007/s00439-019-02031-7 PMID:31144030

Aman Y, Schmauck-Medina T, Hansen M, Morimoto RI, Simon AK, Bjedov I, Palikaras K, Simonsen A, Johansen T, Tavernarakis N, Rubinsztein DC,

Partridge L, Kroemer G, et al. Autophagy in healthy aging and disease. Nat Aging. (2021); 1:634–50. https://doi.org/10.1038/s43587-021-00098-4 PMID:34901876

Levine, B., and Kroemer, G. Biological functions of autophagy genes: a disease perspective. Cell (2019). 176, 11–42. https://doi.org/10.1016/

j.cell.2018.09.048.

Burton, D. G. & Faragher, R. G. Cellular senescence: from growth arrest to immunogenic conversion. Age (Dordr.) (2015). 37, 27

Childs, B. G., Baker, D. J., Kirkland, J. L., Campisi, J. & van Deursen, J. M. Senescence and apoptosis: dueling or complementary cell fates? EMBO Rep.

(2014). 15, 1139–1153

Bettedi L and Foukas LC “Growth factor, energy and nutrient sensing signalling pathways in metabolic ageing.” iogerontology (2017). 18(6): 913–929. [PubMed: 28795262]

López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. (2013); 153:1194–217. https://doi.org/10.1016/j.cell.2013.05.039 PMID:23746838

Mannick, J.B., Teo, G., Bernardo, P., Quinn, D., Russell, K., Klickstein, L., Marshall, W., and Shergill, S. Targeting the biology of ageing with mTOR

inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials. Lancet Healthy Longev. (2021). 2, e250–e262.

https://doi.org/10.1016/S2666-7568(21)00062-3.

Wu, Q., Tian, A.-L., Li, B., Leduc, M., Forveille, S., Hamley, P., Galloway, W., Xie, W., Liu, P., Zhao, L., et al. IGF1 receptor inhibition amplifies the effects of cancer drugs by autophagy and immunedependent mechanisms. J. Immunother. Cancer (2021). 9, e002722. https://doi.org/10.136/jitc-2021-002722.

Sun N, Youle RJ and Finkel T “The Mitochondrial Basis of Aging.” Molecular cell (2016). 61(5): 654–666. [PubMed: 26942670]

Jang JY, Blum A, Liu J and Finkel T “The role of mitochondria in aging.” The Journal of Clinical Investigation (2018). 128(9): 3662–3670. [PubMed: 30059016]

Scheibye-Knudsen M, Fang EF, Croteau DL, Wilson DM 3rd, Bohr VA. Protecting the mitochondrial powerhouse. Trends Cell Biol. (2015); 25:158–70.

https://doi.org/10.1016/j.tcb.2014.11.002 PMID:25499735

Schultz MB and Sinclair DA “When stem cells grow old: phenotypes and mechanisms of stem cell aging.” Development (2016). 143(1): 3–14. [PubMed: 26732838]

Ermolaeva M, Neri F, Ori A and Rudolph KL “Cellular and epigenetic drivers of stem cell ageing.” Nat Rev Mol Cell Biol (2018). 19(9): 594–610.

[PubMed: 29858605]

Franceschi C, Garagnani P, Parini P, Giuliani C and Santoro A “Inflammaging: a new immune– metabolic viewpoint for age-related diseases.” Nature Reviews Endocrinology (2018). 14(10): 576–590.

Fafian-Labora, J.A., and O’Loghlen, A. Classical and nonclassical intercellular communication in senescence and ageing. Trends Cell Biol. (2020). 30, 628–639. https://doi.org/10.1016/j.tcb.2020.05.003.

Levi, N., Papismadov, N., Solomonov, I., Sagi, I., and Krizhanovsky, V. The ECM path of senescence in aging: components and modifiers. FEBS J.

(2020). 287, 2636–2646. https://doi.org/10.1111/febs.15282.

Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. (2018); 15:505–22.

https://doi.org/10.1038/s41569-018-0064-2 PMID:30065258

Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. (2018); 14:576–90. https://doi.org/10.1038/s41574-018-0059-4 PMID:30046148

Kuilman, T. & Peeper, D. S. Senescence-messaging secretome: SMSing cellular stress. Nat. Rev. Cancer (2009).9, 81–94

Campisi, J. & d’Adda di Fagagna, F. Cellular senescence: when bad things happen to good cells. Nat. Rev. Mol. Cell Biol. (2007). 8, 729–740

Lopez-Otin, C., and Kroemer, G. Hallmarks of health. Cell (2021). 184, 33–63. https://doi.org/10.1016/j.cell.2020.11.034.

Wilmanski T, Diener C, Rappaport N, Patwardhan S, Wiedrick J, Lapidus J, Earls JC, Zimmer A, Glusman G, Robinson M, Yurkovich JT, Kado DM,

Cauley JA, et al. Gut microbiome pattern reflects healthy ageing and predicts survival in humans. Nat Metab. (2021); 3:274–86. https://doi.org/10.1038/s42255-021-00348-0 PMID:33619379

Rivero-Segura NA, Bello-Chavolla OY, Barrera-Vázquez OS, Gutierrez-Robledo LM, Gomez-Verjan JC, Promising biomarkers of human aging: in

search of a multi-omics panel to understand the aging process from a multidimensional perspective, Ageing Research Reviews (2020),

https://doi.org/10.1016/j.arr.2020.101164

Biomarkers Definition Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. (2001);

: 89-95. https://doi.org/10.1067/mcp.2001.113989

Evangelou, K. et al. Robust, universal biomarker assay to detect senescent cells in biological specimens. Aging Cell (2017). 16, 192–197

Coppe, J. P. et al. Senescenceassociated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. (2008). 6, 2853–2868

Freund, A., Laberge, R. M., Demaria, M. & Campisi, J. Lamin B1 loss is a senescence-associated biomarker. Mol. Biol. Cell (2012) 23, 2066–2075

Baker, D. J. et al. Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature (2016). 530, 184–189

Jeon, O. H. et al. Clearance of senescent cells prevents the development of post-traumatic osteoarthritis and creates a pro-regenerative environment.

Nat. Med. (2017) 23, 775–781

Baker, D. J. et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature (2011). 479, 232–236

Robbins, P.D., Jurk, D., Khosla, S., Kirkland, J.L., LeBrasseur, N.K., Miller, J.D., Passos, J.F., Pignolo, R.J., Tchkonia, T., and Niedernhofer, L.J. Senolytic drugs: reducing senescent cell viability to extend health span. Annu. Rev. Pharmacol. Toxicol. (2021). 61, 779–803. https://doi.org/10.1146/annurevpharmtox-050120-105018.

Wissler Gerdes, E.O., Misra, A., Netto, J.M.E., Tchkonia, T., and Kirkland, J.L. Strategies for late phase preclinical and early clinical trials of senolytics. Mech. Ageing Dev. (2021). 200, 111591. https://doi.org/10.1016/j.mad.2021.111591.

Zhu, Y., Tchkonia, T., Fuhrmann-Stroissnigg, H., Dai, H.M., Ling, Y.Y., Stout, M.B., Pirtskhalava, T., Giorgadze, N., Johnson, K.O., Giles, C.B., et al. Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell (2016). 15, 428–435. https://doi.org/10.1111/acel.12445.

Triana-Martinez, F., Picallos-Rabina, P., Da Silva-Alvarez, S., Pietrocola, F., Llanos, S., Rodilla, V., Soprano, E., Pedrosa, P., Ferreiro ´ s, A., Barradas, M., et al. Identification and characterization of cardiac glycosides as senolytic compounds. Nat. Commun. (2019). 10, 4731. https://doi.org/10.1038/s41467-019-12888-x.

Ameya S Kulkarni, Ph.D., Sriram Gubbi, M.D., Nir Barzilai, M.D. Benefits of Metformin in Attenuating the Hallmarks of Aging. Cell Metab. (2020)

July 07; 32(1): 15–30. doi:10.1016/j.cmet.2020.04.001.




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