AbstractAverage life span has increased because of medical and environmental factors, but maximal life span remains unchanged. Understanding the mechanisms of aging will help to reduce age-related morbidity and facilitate healthy aging. Unlike female menopause, which is accompanied by an abrupt and permanent cessation of ovarian function (both folliculogenesis and estradiol production), male aging does not result in either cessation of testosterone production or infertility. Although the circulating serum testosterone concentration does decline with aging, in most men this decrease is small, resulting in levels that are generally within the normal range. Age-related hypogonadism has been referred to as andropause or late-onset hypogonadism (LOH), with LOH considered to be the most suitable term for this condition. Hormone therapy (HT) trials have caused both apprehension and confusion about the overall risks and benefits associated with HT treatment. During aging, a gradual decline in the potency of the heat shock response occurs, and this may prevent the repair of protein damage. Thus, the interest in developing pharmacological agents capable of inducing stress responses is growing within the broad frame of hormesis, which underlie strategies for optimal patient treatment of numerous diseases. Vitagenes encode for heat shock proteins, thioredoxin, and sirtuin protein systems. Nutritional antioxidants have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. Here, we focus on possible signaling mechanisms involved in the activation of vitagenes resulting in enhanced defense against bioenergetic defects leading to degeneration and cell death with consequent impact on longevity processes.