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of the global population, neurodegenerative diseases are emerging as a major public health issue. The adoption of a less sedentary lifestyle has been shown to have a beneficial effect on cognitive decline, but the molecular mechanisms responsible are less clear. Here we provide a detailed analysis of the complex molecular, cellular, and systemic mechanisms underlying age-related cognitive decline and how lifestyle choices influence these processes. A review of the evidence from animal models, human studies, and postmortem analyses emphasizes the importance of integrating physical exercise with cognitive, multisensory, and motor stimulation as part of a multifaceted approach to mitigating cognitive decline. We highlight the potential of these non-pharmacological interventions to address key aging hallmarks, such as genomic instability, telomere attrition, and neuroinflammation, and underscore the need for comprehensive and personalized strategies to promote cognitive resilience and healthy aging.<\/jats:p>","DOI":"10.3390\/ijms251910757","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T06:23:18Z","timestamp":1728282198000},"page":"10757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Hidden Dangers of Sedentary Living: Insights into Molecular, Cellular, and Systemic Mechanisms"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7369-2165","authenticated-orcid":false,"given":"Daniel Guerreiro","family":"Diniz","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Microscopia Eletr\u00f4nica, Instituto Evandro Chagas, 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Universidade Federal do Par\u00e1, Bel\u00e9m 66.050-160, Par\u00e1, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4587-580X","authenticated-orcid":false,"given":"Victor Oliveira","family":"da Costa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es em Neurodegenera\u00e7\u00e3o e Infec\u00e7\u00e3o, Hospital Universit\u00e1rio Jo\u00e3o de Barros Barreto, Universidade Federal do Par\u00e1, Bel\u00e9m 66.073-005, Par\u00e1, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6538-0591","authenticated-orcid":false,"given":"Josilayne Patricia Ramos","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es em Neurodegenera\u00e7\u00e3o e Infec\u00e7\u00e3o, Hospital Universit\u00e1rio Jo\u00e3o de Barros Barreto, Universidade Federal do Par\u00e1, Bel\u00e9m 66.073-005, Par\u00e1, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias do Movimento Humano, Universidade Federal do Par\u00e1, Bel\u00e9m 66.050-160, Par\u00e1, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0767-8474","authenticated-orcid":false,"given":"Alessandra Mendon\u00e7a","family":"Tom\u00e1s","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es em Neurodegenera\u00e7\u00e3o e Infec\u00e7\u00e3o, Hospital Universit\u00e1rio Jo\u00e3o de Barros Barreto, Universidade Federal do Par\u00e1, Bel\u00e9m 66.073-005, Par\u00e1, Brazil"},{"name":"Campus Samabaia, Universidade Federal de Goi\u00e1s (EBTT), CEPAE, Goi\u00e2nia 74.001-970, Goi\u00e1s, Brazil"}]},{"given":"Tha\u00eds Cristina","family":"Galdino de Oliveira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es em Neurodegenera\u00e7\u00e3o e Infec\u00e7\u00e3o, Hospital Universit\u00e1rio Jo\u00e3o de Barros Barreto, Universidade Federal do Par\u00e1, Bel\u00e9m 66.073-005, Par\u00e1, Brazil"},{"name":"Faculdade de Ceil\u00e2ndia, Ceil\u00e2ndia, Universidade de Bras\u00edlia, Bras\u00edlia 72.220-900, Brazil"}]},{"given":"Fernanda Cabral","family":"Soares","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es em Neurodegenera\u00e7\u00e3o e Infec\u00e7\u00e3o, Hospital Universit\u00e1rio Jo\u00e3o de Barros Barreto, Universidade Federal do Par\u00e1, Bel\u00e9m 66.073-005, Par\u00e1, Brazil"}]},{"given":"Liliane Dias e Dias","family":"de Macedo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es em Neurodegenera\u00e7\u00e3o e Infec\u00e7\u00e3o, Hospital Universit\u00e1rio Jo\u00e3o de Barros Barreto, Universidade Federal do Par\u00e1, Bel\u00e9m 66.073-005, Par\u00e1, Brazil"},{"name":"Campus Tucurui, Universidade do Estado do Par\u00e1, Tucurui 68.455-210, Par\u00e1, Brazil"}]},{"given":"Naina Yuki Vieira","family":"Jardim","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es em 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