Aging brain

About: Aging brain is a research topic. Over the lifetime, 1255 publications have been published within this topic receiving 66405 citations.

Flavonoids and the aging brain.

Abstract: Like in all other organs, the functional capacity of the human brain deteriorates over time. Pathological events such as oxidative stress, due to the elevated release of free radicals and reactive oxygen or nitrogen species, the subsequently enhanced oxidative modification of lipids, protein, and nucleic acids, and the modulation of apoptotic signaling pathways contribute to loss of brain function. The identification of neuroprotective food components is one strategy to facilitate healthy brain aging. Flavonoids were shown to activate key enzymes in mitochondrial respiration and to protect neuronal cells by acting as antioxidants, thus breaking the vicious cycle of oxidative stress and tissue damage. Furthermore, recent data indicate a favorable effect of flavonoids on neuro-inflammatory events. Whereas most of these effects have been shown in vitro, limited data in vivo are available, suggesting a rather low penetration of flavonoids into the brain. Nevertheless, several reports support the concept that flavonoid intake inhibits certain biochemical processes of brain aging, and might thus prevent to some extent the decline of cognitive functions with aging as well as the development or the course of neurodegenerative diseases. However, more data are needed to assess the true impact of flavonoids on brain aging.

Neuron-specific age-related decreases in dopamine receptor subtype mRNAs.

Abstract: Dopaminergic neurotransmission in the CNS is involved in a number of functions, most notably cognition, affect, and motor control. Increased life expectancy, resulting from recent medical advances, has led to a need for furthering understanding of neurobiology of aging and causes of age-related disabilities in order to improve quality of life (Drachman, 1997). Region-specific changes in the functional integrity of the dopaminergic system have been associated with impairment of motor and cognitive function in humans resulting from age. For example, unbiased estimation studies demonstrate age-related losses in sub-stantia nigra pars compacta (SNpc) neurons, a major source of forebrain dopaminergic projections (Fearnley and Lees, 1991; Ma et al., 1999b). Furthermore, immunohistochemistry and gene expression studies reveal down-regulation of the dopamine (DA) transporter in the SNpc of aged humans and monkeys (Bannon et al., 1992; Bannon and Whitty, 1997; Emborg et al., 1998; Ma et al., 1999a). A loss of DA itself has been demonstrated in normal aging as well (Goldman-Rakic and Brown, 1981; Fearnley and Lees, 1991). Moreover, age-related decreases in D1 and D2 DA receptor subtypes have been demonstrated within the aged human forebrain, including the striatum and hippocampus, by using in vivo imaging techniques combined with DA-selective ligands (Rinne et al., 1993; Volkow et al., 1996; Kaasinen et al., 2000) and in post-mortem studies (Severson et al., 1982; Rinne et al., 1993; Joyce et al., 1998). Thus, pre- and postsynaptic alterations in nigrostriatal dopaminergic circuitry exist in the aging brain and may account for alterations in motor function (Fearnley and Lees, 1991; Emborg et al., 1998). The hippocampal formation is another brain region that receives dopaminergic projections from the mesencephalon, specifically the vental tegmentum (Scatton et al., 1980; Verney et al., 1985), and is also vulnerable to aging. Previous studies in rats have demonstrated significant age-related decreases in DA levels (Godefroy et al., 1989; Miguez et al., 1999) and DA receptors (Amenta et al., 2001) in the hippocampus of aged rats. Parallel alterations in humans have been demonstrated in brain regions associated with cognition during aging, including the hippocampus and temporal neocortex (Rinne, 1987; Seeman et al., 1987; Camps et al., 1989; Cortes et al., 1989; Rinne et al., 1990; Kaasinen et al., 2000; Inoue et al., 2001). At present, few primary data exist regarding the cellular specificity of age-related decline of DA receptor expression within the human temporal lobe. Primary difficulties in evaluating DA receptor subtypes in temporal lobe and other cortical regions include a moderate DA receptor subtype density and the paucity of high-affinity/receptor-selective ligands for D1–D5 DA receptors. Alternatively, use of gene expression technologies provides the means to evaluate selectively all DA receptor subtypes in discrete brain regions. For example, Meador-Woodruff and colleagues (Meador-Woodruff, 1994; Meador-Woodruff et al., 1996) have demonstrated the presence of mRNAs encoding the five known DA receptors in the human hippocampal formation by using in situ hybridization. These studies suggest a heterogeneous distribution within subfields of the hippocampal formation and laminae of the temporal lobe. However, the relative abundance of DA receptor mRNAs in specific neuronal populations making up these subregions remains elusive. In situ hybridization allows the analysis of a given mRNA in a single neuron, yet the sensitivity may not allow the analysis of low-abundance mRNAs or the means to evaluate numerous transcripts within the same tissue section. Moreover, reliance on regional assessment of gene expression emphasizes transcripts contained in the majority of neuronal and glial populations and/or transcripts in highest abundance in the region, which may not adequately reflect alterations in gene expression in target neuronal populations. Single-cell molecular biological procedures allow precise localization of changes in gene expression within brain regions (Eberwine et al., 1992; Surmeier et al., 1996; Ginsberg et al., 1999, 2000; Hemby et al., 2002). In the present study, single-cell gene expression procedures were used to assess the relative abundance of DA receptor mRNA levels in CA1 pyramidal neurons and entorhinal cortex (EC) layer II stellate neurons from human post-mortem brain tissue, permitting precise dissection and detailed molecular characterization of specific neuronal populations that are the principal neuronal conduits of information to the hippocampal-entorhinal circuit.

Cellular Senescence in Brain Aging.

Abstract: Aging of the brain can manifest itself as a memory and cognitive decline, which has been shown to frequently coincide with changes in the structural plasticity of dendritic spines. Decreased number and maturity of spines in aged animals and humans, together with changes in synaptic transmission, may reflect aberrant neuronal plasticity directly associated with impaired brain functions. In extreme, a neurodegenerative disease, which completely devastates the basic functions of the brain, may develop. While cellular senescence in peripheral tissues has recently been linked to aging and a number of aging-related disorders, its involvement in brain aging is just beginning to be explored. However, accumulated evidence suggests that cell senescence may play a role in the aging of the brain, as it has been documented in other organs. Senescent cells stop dividing and shift their activity to strengthen the secretory function, which leads to the acquisition of the so called senescence-associated secretory phenotype (SASP). Senescent cells have also other characteristics, such as altered morphology and proteostasis, decreased propensity to undergo apoptosis, autophagy impairment, accumulation of lipid droplets, increased activity of senescence-associated-β-galactosidase (SA-β-gal), and epigenetic alterations, including DNA methylation, chromatin remodeling, and histone post-translational modifications that, in consequence, result in altered gene expression. Proliferation-competent glial cells can undergo senescence both in vitro and in vivo, and they likely participate in neuroinflammation, which is characteristic for the aging brain. However, apart from proliferation-competent glial cells, the brain consists of post-mitotic neurons. Interestingly, it has emerged recently, that non-proliferating neuronal cells present in the brain or cultivated in vitro can also have some hallmarks, including SASP, typical for senescent cells that ceased to divide. It has been documented that so called senolytics, which by definition, eliminate senescent cells, can improve cognitive ability in mice models. In this review, we ask questions about the role of senescent brain cells in brain plasticity and cognitive functions impairments and how senolytics can improve them. We will discuss whether neuronal plasticity, defined as morphological and functional changes at the level of neurons and dendritic spines, can be the hallmark of neuronal senescence susceptible to the effects of senolytics.