Dietary amelioration of locomotor, neurotransmitter and mitochondrial aging

Abstract

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.

A complex dietary supplement augments spatial learning, brain mass, and mitochondrial electron transport chain activity in aging mice

“…We previously reported a 56% elevation in activity of mitochondrial complex III activity in brains of supplemented mice by ∼2 years of age (Aksenov et al 2010). Similarly, we show here that supplementation achieved a ∼65% increase in complex IV activity by ∼2 years of age.…”

“…Daily dosages were derived from recommended human values adjusted for body size and the higher metabolic rate of mice. Supplemented mice received 1 dose/day of DSP that was soaked onto small pieces of bagel in their home cages (details in Lemon et al 2003;Aksenov et al 2010). All mice avidly ate the supplement confirming no issues concerning palatability.…”

“…Age-related accumulation of oxidative damage in brain contributes to cognitive deterioration (Nicolle et al 2001;Dröge and Schipper 2007;Rollo 2009), but recently, energy metabolism (i.e., age-related decline in mitochondrial function) has also been highlighted (Navarro and Boveris 2007;Aksenov et al 2010). Mitochondrial complex I dysfunction is strongly implicated in PD (Navarro and Boveris 2009), and complex III is also associated with generation of reactive oxygen species (ROS) relevant to aging (Chen et al 2004;Muller et al 2004).…”

“…It entirely prevented age-related declines in spontaneous motor activity and elevated brain mitochondrial function (complex III) in old age while reducing the rate of free radical generation. Levels of striatal neuropeptide Y were elevated in supplemented normal mice (Aksenov et al 2010). Additionally, the DSP protected mice from oxidative damage associated with aging and radiation (Lemon et al 2008a, b;Aksenov et al 2010).…”

“…Levels of striatal neuropeptide Y were elevated in supplemented normal mice (Aksenov et al 2010). Additionally, the DSP protected mice from oxidative damage associated with aging and radiation (Lemon et al 2008a, b;Aksenov et al 2010). Previous cognitive benefits of the DSP were demonstrated in transgenic growth hormone mice that express accelerated aging and rapid cognitive decline (Lemon et al 2003).…”