Dopamine and Aging: Intersecting Facets

Abstract

Aging encompasses life itself so understanding requires frameworks that forge unity amidst complexity. The free radical theory of aging is one example. The original focus on damage was augmented recently by appreciation that reactive oxygen and nitrogen species are essential to normal signaling and cell function. This paradigm is currently undergoing an explosive expansion fueled by the discovery that regulatory organization is a merry-go-round of redox cycling seamlessly fused to endogenous clocks. This might best be described as an "Electroplasmic Cycle." This is certainly applicable to dopaminergic neurons with their exceptional metabolic, electrical and rhythmic properties. Here I review normal aging of dopamine systems to highlight them as a valuable model. I then examine the possible integration of free radical and ion channel theories of aging. Finally, I incorporate clocks and explore the multifaceted implications of electroplasmic cycles with special emphasis on dopamine.

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

“…Moreover, the threshold nature of this learning suggests that higher-order processes associated with "insight" may be favored by the supplement. Cognitive decline is one of the most reliable biomarkers of aging in animals (Carney et al 1991;Rollo 2009). Thus, prevention of cognitive decline in normal animals spanning ages of 12 to 27 months attests to great efficacy of the supplement (Fig.…”

“…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).…”

Comparing the effects of food restriction and overeating on brain reward systems

“…Similar to patterns seen in populations who overeat, a reduction in DA functioning is associated with ageing (Rollo, 2009). For example, striatal D2 receptors have been shown to decrease approximately 7.9% per decade in humans (Volkow et al, 1996), and D2 transporters have been shown to decrease as people age (Volkow et al, 1994).…”

7tm Receptors

“…Alexander et al Rollo CD (2009 ]ET-1 (Molenaar et al, 1992), sarafotoxin S6c (Russell and Davenport, 1996), IRL1620 (Watakabe et al, 1992), BQ3020 (Russell and Davenport, 1996) Selective antagonists A127722 (9.2-10.5, Opgenorth et al, 1996), LU135252 (8.9, Riechers et al, 1996, SB234551 (8.7-9.0, Ohlstein et al, 1998), PD156707 (8.2-8.5, Maguire et al, 1997), FR139317 (7.3-7.9, Maguire and Davenport, 1995), BQ123 (6.9-7.4, Maguire and Davenport, 1995 ]ET-1 (0.2 nM, Molenaar et al, 1992) Subtypes of the ETB receptor have been proposed, although gene disruption studies in mice suggest that the heterogeneity results from a single gene product (Mizuguchi et al, 1997). Breu V et al (1996).…”