Modulation of epigenetic signatures of aging: the impact of exercise on DNA methylation in adults and older adults

• Ano de defesa: 2025
• Autor(a) principal: Rodrigues, Guilherme da Silva
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: DNA methylation; Envelhecimento saudável; Exercício físico; Força muscular; Healthy aging; Metilação do DNA; Muscle strength; Physical exercise
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/17/17138/tde-04122025-172506/

This thesis investigated how physical exercise modulates the epigenetic signatures of aging, with an emphasis on DNA methylation in older adults, particularly women aged 50 to 70 years. Through four complementary studies, the effects of exercise training on epigenetic markers associated with muscle function, biological age, cognition, and the risk of chronic diseases such as Alzheimer\'s disease were explored. The first study, a review, highlighted the molecular mechanisms by which exercise influences DNA methylation, underscoring its potential to modulate biological aging and reinforcing the importance of tailoring strategies based on individual variability. The second study employed a multi-omic approach to identify genetic variants and epigenetic signatures associated with muscle strength in postmenopausal women, revealing that high levels of the protein BMP1, regulated by methylation, were positively associated with strength and bone health. The third study identified methylation changes in genes related to Alzheimer\'s disease after 14 weeks of combined training, suggesting a potential protective role of exercise on genetic regions critical for neurodegeneration. Finally, the fourth study demonstrated that eight weeks of combined training (aerobic + resistance) significantly reduced epigenetic age in women with accelerated aging, in addition to improving functional parameters, blood pressure, and cognition. Collectively, the findings of this thesis support the notion that physical exercise is an effective intervention to modulate epigenetic signatures associated with aging, with meaningful impacts on muscle function, brain health, and biological age. These results reinforce the role of exercise as a non-pharmacological strategy to promote healthy aging through molecular mechanisms.