GENETIC BASES OF AGING: A BRIEF REVIEW OF THE LITERATURE
DOI:
https://doi.org/10.63330/armv1n4-006Keywords:
Aging, Genetics, Telomeres, Cellular senescence, EpigeneticsAbstract
Ageing is a complex biological process, influenced by intrinsic (genetic) and extrinsic (environmental) factors. Genetic bases play a crucial role in determining longevity and health at advanced ages. Among the main associated mechanisms are cellular senescence, telomere shortening, the accumulation of somatic mutations and the deregulation of molecular signaling pathways, such as those involved in metabolism and the stress response. Genes such as FOXO3, SIRT1 and TP53 stand out for regulating key aging processes, including DNA repair, autophagy and resistance to oxidative stress. In addition, epigenetic modifications, such as DNA methylation and changes in histones, influence gene expression throughout life. Future interventions, such as gene therapies and drugs that modulate these pathways (for example, sirtuin activators or senescence inhibitors), promise to slow aging and promote healthy aging. Research into epigenetics and personalized medicine could revolutionize the treatment of age-related diseases, extending quality life expectancy.
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ALMEIDA, Arthur José Pontes Oliveira et al. Envelhecimento: aspectos moleculares e suas implicações sobre o sistema cardiovascular. 2017. Disponível em: https://repositorio.ufpb.br/jspui/handle/123456789/3521. Acesso em: 8 de mai. 2025.
ARMANIOS, Mary; BLACKBURN, Elizabeth H. The telomere syndromes. Nature Reviews Genetics, v. 13, n. 10, p. 693-704, 2012. Disponível em: https://www.nature.com/articles/nrg3246. Acesso: 12 de abr. 2025.
BLACKBURN, Elizabeth H.; EPEL, Elissa S.; LIN, Jue. Human telomere biology: a contributory and interactive factor in aging, disease risks, and protection. Science, v. 350, n. 6265, p. 1193-1198, 2015. Disponível em: https://www.science.org/doi/abs/10.1126/science.aab3389. Acesso em: 13 de abr. 2025.
BORDONE, Laura et al. SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging cell, v. 6, n. 6, p. 759-767, 2007. Disponível em: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1474-9726.2007.00335.x. Acesso: 8 de mai. 2025.
BORDONE, Laura et al. SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging cell, v. 6, n. 6, p. 759-767, 2007. Disponível em: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1474-9726.2007.00335.x. Acesso: 13 de abr.2025.
DAVY, Philip MC et al. FOXO3 and exceptional longevity: insights from hydra to humans. In: Current topics in developmental biology. Academic Press, 2018. p. 193-212.Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S0070215317300509. Acesso: 13 de abr.2025.
Garcia, D., & Attardi, L. D. (2022). TP53 and aging. Aging Cell, 21(3), e13603.
GUARENTE, Leonard. Sirtuins, aging, and metabolism. In: Cold Spring Harbor symposia on quantitative biology. Cold Spring Harbor Laboratory Press, 2011. p. 81-90. Disponível em: https://symposium.cshlp.org/content/76/81.short.Acesso: 13 de abr.2025.
HORVATH, Steve; RAJ, Kenneth. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nature reviews genetics, v. 19, n. 6, p. 371-384, 2018. Jaskelioff, M., et al. (2011). Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature, 469(7328), 102-106. Disponível em: https://www.nature.com/articles/s41576-018-0004-3. Acesso: 13 de abr.2025.
IMAI, Shin-ichiro; GUARENTE, Leonard. NAD+ and sirtuins in aging and disease. Trends in cell biology, v. 24, n. 8, p. 464-471, 2014. Disponível em: https://www.cell.com/trends/cell-biology/abstract/S0962-8924(14)00063 4?elsca1=etoc&elsca3=0962-8924_201408_24_8_&elsca2=email&elsca4=Cell+Press. Acesso: 8 de mai. 2025.
IMAI, Shin-ichiro; GUARENTE, Leonard. NAD+ and sirtuins in aging and disease. Trends in cell biology, v. 24, n. 8, p. 464-471, 2014. Disponível em: https://www.cell.com/trends/cell-biology/abstract/S0962-8924(14)00063-4?elsca1=etoc&elsca3=0962-8924_201408_24_8_&elsca2=email&elsca4=Cell+Press. Acesso: 13 de abr.2025.
JASKELIOFF, Mariela et al. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature, v. 469, n. 7328, p. 102-106, 2011. Disponível em: https://www.nature.com/articles/nature09603. Acesso: 13 de abr.2025.
JONES, Meaghan J.; GOODMAN, Sarah J.; KOBOR, Michael S. DNA methylation and healthy human aging. Aging cell, v. 14, n. 6, p. 924-932, 2015. Disponível em: https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12349. Acesso: 13 de abr.2025.
KENNEDY, Brian K. et al. Geroscience: linking aging to chronic disease. Cell, v. 159, n. 4, p. 709-713, 2014. Disponível em: https://www.cell.com/cell/fulltext/S0092-8674(14)01366-X. Acesso: 8 de mai. 2025.
KENNEDY, Brian K. et al. Geroscience: linking aging to chronic disease. Cell, v. 159, n. 4, p. 709-713, 2014. Disponível em: https://www.cell.com/cell/fulltext/S0092-8674(14)01366-X. Acesso: 13 de abr.2025.
KENYON, Cynthia J. The genetics of ageing. Nature, v. 464, n. 7288, p. 504-512, 2010. Disponível em: https://www.nature.com/articles/nature08980. Acesso: 13 de abr.2025.
LÓPEZ-OTÍN, Carlos et al. The hallmarks of aging. Cell, v. 153, n. 6, p. 1194-1217, 2013. Disponível em: https://www.cell.com/cell/fulltext/S0092-8674(13)00645-4. Acesso: 13 de abr.2025.
MAIER, Bernhard et al. Modulation of mammalian life span by the short isoform of p53. Genes & development, v. 18, n. 3, p. 306-319, 2004. Disponível em: https://genesdev.cshlp.org/content/18/3/306.short. Acesso: 8 de mai. 2025.
MORRIS, Martha Clare et al. MIND diet slows cognitive decline with aging. Alzheimer's & dementia, v. 11, n. 9, p. 1015-1022, 2015. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S1552526015001946. Acesso: 8 de mai. 2025.
SEN, Payel et al. Epigenetic mechanisms of longevity and aging. Cell, v. 166, n. 4, p. 822-839, 2016. Disponível em: https://www.cell.com/fulltext/S0092-8674(16)31000-5. Acesso: 13 de abr.2025.
SHAY, Jerry W.; WRIGHT, Woodring E. Telomeres and telomerase: three decades of progress. Nature Reviews Genetics, v. 20, n. 5, p. 299-309, 2019. Disponível em: https://www.nature.com/articles/s41576-019-0099-1. Acesso: 13 de abr.2025.
SMITH-VIKOS, Thalyana; SLACK, Frank J. MicroRNAs and their roles in aging. Journal of cell science, v. 125, n. 1, p. 7-17, 2012. Disponível em: https://journals.biologists.com/jcs/article/125/1/7/32215/MicroRNAs-and-their-roles-in-aging. Acesso: 13 de abr.2025.
SUH, Yousin et al. Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proceedings of the National Academy of Sciences, v. 105, n. 9, p. 3438-3442, 2008. Disponível em: https://www.pnas.org/doi/abs/10.1073/pnas.0705467105. Acesso: 8 de mai. 2025.
TYNER, Stuart D. et al. p53 mutant mice that display early ageing-associated phenotypes. Nature, v. 415, n. 6867, p. 45-53, 2002. Disponível em: https://www.nature.com/articles/415045a. Acesso: 8 de mai. 2025.
VAISERMAN, A. M.; PASYUKOVA, Elena G. Epigenetic drugs: a novel anti-aging strategy?. Frontiers in genetics, v. 3, p. 224, 2012. Disponível em: https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2012.00224/full. Acesso: 13 de abr.2025.
VON ZGLINICKI, Thomas. Oxidative stress shortens telomeres. Trends in biochemical sciences, v. 27, n. 7, p. 339-344, 2002. Disponível em: https://www.cell.com/trends/biochemical-sciences/abstract/S0968-0004(02)02110-2. Acesso: 13 de abr.2025.
ZHANG, Weiqi et al. The ageing epigenome and its rejuvenation. Nature reviews Molecular cell biology, v. 21, n. 3, p. 137-150, 2020. Disponível em: https://www.nature.com/articles/s41580-019-0204-5. Acesso: 13 de abr.2025.
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Copyright (c) 2025 Gregório Otto Bento de Oliveira, Ayanne Stela Vieira Gomes da Silva, Grazieli Aparecida Huppes, Diego de Carvalho Maia, Victor Martins Aguilar Escobar, Leonardo Domingues Ramos, Eva dos Santos Silva, Maria Clara da Silva Goersch, Luciana Gobbi, Gutemberg Delfino Sousa (Autor)
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