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However, it is unknown how loneliness and social isolation are differentially associated with physical and mental components of health-related quality of life (HRQoL). We aimed to examine this association, overall and by sex. We used data obtained from 1808 community-dwelling individuals older than 65\u00a0years participating in the Seniors-ENRICA 2 cohort. Baseline phase was conducted between December 2015 and June 2017, and then a two-year follow-up period was considered. Loneliness was assessed using the three-item UCLA Loneliness Scale, while social isolation was measured using a four-component index, which included contact with family members and friends. HRQoL was assessed with the SF-12 questionnaire, using its physical and mental components. Multivariable linear regression models were used in the overall sample and stratified by sex. Higher scores in loneliness were associated with a decrease in the physical HRQoL [Coef.\u2009=\u2009 \u2212\u20090.31, 95% confidence interval\u2009=\u2009(\u2212\u20090.60, \u2212\u20090.01),\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.042] and mental HRQoL [\u2212\u20090.76 (\u2212\u20091.11, \u2212\u20090.43),\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001]. There was no significant association between social isolation and HRQoL. The association between loneliness and the physical HRQoL was different by sex (\n                    <jats:italic>p<\/jats:italic>\n                    for interaction term\u2009=\u20090.028), and higher levels of loneliness were related to lower physical HRQoL scores only in women [\u2212\u20090.53 (\u2212\u20090.92, \u2212\u20090.14),\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007]. Loneliness had an independent association with HRQoL. This relationship seems to be stronger in women, which highlights the importance of a sex perspective in interventions to improve the HRQoL.\n                  <\/jats:p>","DOI":"10.1007\/s10433-025-00905-6","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T15:24:14Z","timestamp":1771255454000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Loneliness, social isolation, and health-related quality of life in older adults"],"prefix":"10.1007","volume":"23","author":[{"given":"Marcela","family":"Dur\u00e1n-Arias","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Humberto","family":"Y\u00e9venes-Briones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 R.","family":"Banegas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Rodr\u00edguez-Artalejo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Lopez-Garcia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco F\u00e9lix","family":"Caballero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"905_CR1","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.ssresearch.2017.08.003","volume":"68","author":"F Acciai","year":"2017","unstructured":"Acciai F, Hardy M (2017) Depression in later life: a closer look at the gender gap. 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