Aging degrades motivation, cognition, sensory modalities and physical capacities, essentially dimming zestful living. Bradykinesis (declining physical movement) is a highly reliable biomarker of aging and mortality risk. Mice fed a complex dietary supplement (DSP) designed to ameliorate five mechanisms associated with aging showed no loss of total daily locomotion compared with >50% decrement in old untreated mice. This was associated with boosted striatal neuropeptide Y, reversal of age-related declines in mitochondrial complex III activity in brain and amelioration of oxidative stress (brain protein carbonyls). Supplemented mice expressed approximately 50% fewer mitochondrial protein carbonyls per unit of complex III activity. Reduction of free radical production by mitochondria may explain the exceptional longevity of birds and dietary restricted animals and no DSP is known to impact this mechanism. Functional benefits greatly exceeded the modest longevity increases documented for supplemented normal mice. Regardless, for aging humans maintaining zestful health and performance into later years may provide greater social and economic benefits than simply prolonging lifespan. Although identifying the role of specific ingredients and interactions remains outstanding, results provide proof of principle that complex dietary cocktails can powerfully ameliorate biomarkers of aging and modulate mechanisms considered ultimate goals for aging interventions.

Animal and human studies provide strong and consistent evidence suggesting that estrogen is able to regulate the serotonin pathway at various levels. The general trend that emerges is that estrogen administration increases serotonin availability by altering mRNA and protein levels of various serotonin markers and by decreasing serotonin breakdown. These effects may have direct implications on female mood disorders such as premenstrual disorders and depression during pregnancy, postpartum, and during the menopausal transition.

Estrogen is regulated through two intracellular receptors, estrogen receptor alpha and estrogen receptor beta, through a classic nuclear-initiated response. Recently, estrogen has also been shown to act more rapidly and it is proposed that these fast effects may be the consequence of membrane localized estrogen receptors that act through the second messengers. Although the identification of these receptors remains to be elucidated, the possible role that they play in female-specific mood disorders is of particular interest, especially in times of major hormonal fluctuation. The purpose of this mini-review is to outline the recent literature regarding the rapid effects of estrogen, to explore the intracellular signaling pathways that may be involved in this regulation as well as the connection between estrogen and serotonin neurotransmission and finally, to look into the antidepressant role that estrogen may have, with particular emphasis on female-specific mood disorders.

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