Exercise and Phytochemicals as Modulators of Redox Homeostasis in Aging

Reduced resilience to physiological stress, including impaired redox signaling, is a hallmark of aging that contributes to chronic disease risk. The transcription factor Nrf2 is widely considered a master regulator of redox homeostasis. Although exercise is a potent activator of Nrf2 signaling, exercise-induced Nrf2 activation is attenuated with aging. One emerging strategy to restore or potentiate exercise-induced Nrf2 activation in older adults is to combine exercise with phytochemicals known to modulate Nrf2 activity. This review summarizes redox homeostasis and Nrf2 signaling during exercise and training, how these processes are impacted during aging, and the current evidence for and against combining phytochemicals known to activate Nrf2 signaling (i.e., astaxanthin, curcumin, and sulforaphane) with exercise in older populations. We also highlight mechanistic differences between exercise- and phytochemical-induced Nrf2 activation and consider whether combining these two interventions could enhance redox resilience more than either alone. Despite early signs of promise (largely derived from cell culture and rodent studies), current evidence is insufficient to fully support the benefits of combining phytochemicals with exercise, with limited clinical data in aging populations. Nevertheless, the rationale for further research is compelling, and we outline key translational challenges and priorities for future trials to advance the field forward.