Exploring age-related influences on COVID-19 severity and therapeutic approaches for older patients

• COVID-19 mortality rates are markedly higher in older patients. • Older patients are more vulnerable to COVID-19 due to age-related declines in immunity and heightened baseline inflammation. • Comorbidities like cardiovascular disease and diabetes further elevate COVID-19 vulnerability in older populations. • Treatments like senolytics, antioxidants, and vitamin D, based on aging research, may help improve COVID-19 outcomes in older adults. Older adults experience higher rates of COVID-19-related morbidity and mortality compared to younger populations. This increased vulnerability is driven by age-associated biological changes affecting immune function and inflammatory regulation. This review aimed to synthesize current evidence on the biological mechanisms underlying the heightened risk of severe COVID-19 in older adults and to explore therapeutic strategies from a geroscience perspective. A narrative literature review was conducted using PubMed, Scopus, and Google Scholar to identify peer-reviewed articles published between January 2020 and December 2024. Studies were included if they focused on aging-related biological factors, immunological changes, or therapeutic interventions relevant to COVID-19 in adults aged 60 and older. The review identified key mechanisms including immunosenescence, inflammaging, altered human angiotensin-converting enzyme 2 (ACE2) expression, increased oxidative stress, and reduced autophagic activity that contribute to COVID-19 severity in older adults. The presence of comorbid conditions, particularly cardiovascular disease and diabetes, further amplifies this vulnerability. Several therapeutic approaches, including senolytics, antioxidants, vitamin D supplementation, and precision medicine guided by biological aging, show potential to mitigate adverse outcomes. Aging-related biological changes play a critical role in the pathogenesis of COVID-19 among older adults. Integrating geroscience-based interventions into COVID-19 management may help reduce severity and improve outcomes in this vulnerable population.