original：
《Targeting the hallmarks of aging to improve influenza vaccine responses in older adults》
Abstract
Age-related declines in immune responses pose significant challenges to defending against disease in later life. Influenza infection remains a major health burden in older adults, with survivors often experiencing substantial functional impairment. Despite the availability of vaccines designed specifically for older adults, the health impact of influenza remains high, and the overall protective efficacy of these vaccines in this population is suboptimal. Recent geroscience research has highlighted the potential of targeting aging processes to ameliorate multiple age-related functional declines. Indeed, vaccine immune responses are highly coordinated processes, and the poor vaccine outcomes in older adults result from the cumulative effect of multiple age-related physiological changes rather than a single factor. This review focuses on the multifaceted nature of impaired vaccine responses in older adults and outlines potential geroscience-guided strategies to address these limitations. More specifically, we propose that novel vaccine development and intervention strategies targeting the core hallmarks of aging—including inflammation, cellular senescence, microbiome dysbiosis, and mitochondrial dysfunction—may enhance vaccine responses in older adults and improve overall immune fitness. Identifying new interventions that strengthen the protective effects of vaccines is critical to reducing the severe burden of influenza and other infectious diseases in older populations.
Key Section: Geroscience-Guided Interventions for Vaccine Optimization
A growing body of evidence supports the notion that targeting aging-related pathways can improve immune function in older adults, thereby enhancing vaccine responses. Potential interventions include pharmacological agents, nutraceuticals, and lifestyle modifications that address the hallmarks of aging. For example, compounds that modulate inflammation (e.g., metformin, rapamycin analogs) or enhance mitochondrial function (e.g., resveratrol, sulforaphane) have shown promise in preclinical and early clinical studies for improving age-related immune declines. Sulforaphane, a naturally occurring isothiocyanate found in cruciferous vegetables, has been identified as a candidate due to its ability to target oxidative stress and mitochondrial dysfunction—key drivers of immune senescence. While direct clinical evidence linking sulforaphane to improved influenza vaccine responses is emerging, preclinical data support its potential as part of a multimodal approach to enhance immune fitness in older adults.