Mechanisms of ageing and development
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Nucleus accumbens (ACC) of young (4 months old) and aged (24 months old) Wistar rats were perfused with dopamine (DA) uptake blocker, cocaine, or the serotonin (5-HT) selective reuptake inhibitor, fluoxetine, through the microdialysis probe membrane, used to assess the dopamine transporter (DAT) or serotonin transporter (SERT) modulation. The basal extracellular DA release in the ACC was significantly lower in aged rats than young rats. Analysis of DA and 5-HT concentrations in the ACC with increased positive GFAP revealed that DA and DOPAC levels of aged rats were decreased to 55 and 60% of those in young rats, respectively. ⋯ Co-perfusion with fluoxetine showed lower magnitude of the increased DA release in aged rats. It appears that the DAT and SERT system responds initially to ACC cell loss with age, and that especially ACC DAT in the aged rat is more degenerative compared with the young rats. These findings suggest that the serotonergic system with SERT in the remaining ACC neurons show an early adaptive response and resistance to the normal aging and maintain the multiple regulatory system in the ACC despite neural loss since the dopaminergic neurons in the aged animals are vulnerable to aging.
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In this report the olfactory bulbs (OB) were removed from 5-6 month, 15-16 month and 25-26 month male Fischer 344 rats and assayed for concentrations of monoamines and their metabolites using HPLC-EC. Concentrations of norepinephrine were significantly greater in 25-26 and 15-16 compared to the 5-6 month old rats. ⋯ These data show some of the age related changes which occur in the monoamines of the OB of the Fischer 344 rat. The salient bi-directional changes which are observed between norepinephrine and its metabolite, MHPG, are particularly intriguing since they reveal some of the mechanistic alterations that occur in the OB noradrenergic system, which may underlie the age related changes in olfactory related memory/recognition processes.
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A theory concerning the molecular basis of rejuvenation is presented that postulates a central role for cell proliferation. This theory assumes that aging is due to the accumulation of multiple forms of molecular damage and that rejuvenation is due to repair. The advantages of proliferation as a means of repair are described and it is proposed that cell proliferation is required for full rejuvenation. This proliferation theory offers several advantages: a different perspective on the question of which organisms age; an explanation of aging-related phenomena that are not well handled by traditional aging theories; a novel approach to altering the aging rate; and testable implications for the design of new experimental systems and therapeutic interventions.