Brain Ca 2 regulatory processes are altered during aging, disrupting neuronal, and cognitive functions. In hippocampal pyramidal neurons, the Ca 2 -dependent slow afterhyperpolarization (sAHP) exhibits an increase with aging, which correlates with memory impairment. The increased sAHP results from elevated L-type Ca 2 channel activity and ryanodine receptor (RyR)-mediated Ca 2 release, but unde...

Significant advances in medical science during the last century have resulted in a gradual, but highly significant, increase in human life span. On the surface this is a great achievement, but as people age, their cognitive function is threatened by the normal aging process, as well as increasing risk for dementia.1 The precise cause of the neuronal degeneration underlying these disorders, and ...

Perturbed neuronal proteostasis is a salient feature shared by both aging and protein misfolding disorders. The proteostasis network controls the health of the proteome by integrating pathways involved in protein synthesis, folding, trafficking, secretion, and their degradation. A reduction in the buffering capacity of the proteostasis network during aging may increase the risk to undergo neuro...

Aging is a major risk factor for Alzheimer's disease (AD). Aggregation of amyloid beta (Aβ) in cerebral cortex and hippocampus is a hallmark of AD. Many factors have been identified as causative elements for onset and progression of AD; for instance, tau seems to mediate the neuronal toxicity of Aβ, and downregulation of macroautophagy (autophagy) is thought to be a causative element of AD path...

Uncoupling proteins (UCPs) are mitochondrial inner membrane proteins that function to dissipate proton motive force and mitochondrial membrane potential. One UCP has been identified in Caenorhabditis elegans (C. elegans), namely UCP-4. In this study, we examined its expression and localization using a GFP marker in C. elegans. ucp-4 was expressed throughout the body from early embryo to aged ad...

Aging is a major risk factor in many forms of late-onset neurodegenerative disorders. The ability to recapitulate age-related characteristics of human neurons in culture will offer unprecedented opportunities to study the biological processes underlying neuronal aging. Here, we show that using a recently demonstrated microRNA-based cellular reprogramming approach, human fibroblasts from postnat...

The ability of injured axons to regenerate declines with age, yet the mechanisms that regulate axon regeneration in response to age are not known. Here we show that axon regeneration in aging C. elegans motor neurons is inhibited by the conserved insulin/IGF1 receptor DAF-2. DAF-2's function in regeneration is mediated by intrinsic neuronal activity of the forkhead transcription factor DAF-16/F...

It has been long believed that cathepsins compensate for each other because of their overlapping substrate specificities. However, there is increasing evidence that disturbance of the normal balance of their enzymatic activities is the first insult in brain aging and age-related diseases. The imbalance of cathepsins may further cause age-related neuropathological changes such as accumulation of...

Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conse...

Recent studies indicate that the cognitive processes mediated by the prefrontal cortex, such as working memory, are impaired during normal aging. These disturbances in cortical function may be a consequence of abnormalities in neocortical circuits, even though the numbers of cortical neurons are preserved in normal aging. We performed retrograde tract-tracing of cortical projections connecting ...