Improving the effectiveness of anti-aging modalities by using the constrained disorder principle-based management algorithms

Aging is a complex biological process with multifactorial nature underlined by genetic, environmental, and social factors. In the present paper, we review several mechanisms of aging and the pre-clinically and clinically studied anti-aging therapies. Variability characterizes biological processes from the genome to cellular organelles, biochemical processes, and whole organs’ function. Aging is associated with alterations in the degrees of variability and complexity of systems. The constrained disorder principle defines living organisms based on their inherent disorder within arbitrary boundaries and defines aging as having a lower variability or moving outside the boundaries of variability. We focus on associations between variability and hallmarks of aging and discuss the roles of disorder and variability of systems in the pathogenesis of aging. The paper presents the concept of implementing the constrained disease principle-based second-generation artificial intelligence systems for improving anti-aging modalities. The platform uses constrained noise to enhance systems’ efficiency and slow the aging process. Described is the potential use of second-generation artificial intelligence systems in patients with chronic disease and its implications for the aged population

Proteolysis and membrane capture of F-spondin generates combinatorial guidance cues from a single molecule

The formation of neuronal networks is governed by a limited number of guidance molecules, yet it is immensely complex. The complexity of guidance cues is augmented by posttranslational modification of guidance molecules and their receptors. We report here that cleavage of the floor plate guidance molecule F-spondin generates two functionally opposing fragments: a short-range repellent protein deposited in the membrane of floor plate cells and an adhesive protein that accumulates at the basement membrane. Their coordinated activity, acting respectively as a short-range repellant and a permissive short-range attractant, constricts commissural axons to the basement membrane beneath the floor plate cells. We further demonstrate that the repulsive activity of the inhibitory fragment of F-spondin requires its presentation by the lipoprotein receptor–related protein (LRP) receptors apolipoprotein E receptor 2, LRP2/megalin, and LRP4, which are expressed in the floor plate. Thus, proteolysis and membrane interaction coordinate combinatorial guidance signaling originating from a single guidance cue

Investigating the Relationship Between Sleeping Brain Activity and Neural Differentiation of Competing Memories

To accurately remember information from our past, we must not forget it and we must not confuse it with related information. In other words, we want our memories to be stable in our brain’s long-term storage and to be organized in such a way that we can access them without interference from competing memories. Memory models suggest that memory reactivation, which can occur during either wakefulness or sleep, is the key to stabilizing long-term memories and differentiating them from competing ones. In regards to sleep specifically, there is evidence that non-rapid eye movement (NREM) sleep spindle events and rapid eye movement (REM) sleep are linked to memory reactivation. Here, we used a pre-existing fMRI dataset to measure how much two memory representations move apart from one another, a measure called neural differentiation (study design by Dr. K Norman and Dr. E McDevitt; data collection by Dr. E McDevitt). We investigated if spindles and REM sleep, which occurred during an intervening period of sleep between neural measurements, were correlated with neural differentiation using EEG data and source localization techniques. We contrasted periods of spindle activity with equivalent periods of non-spindle activity to spatially localize brain areas with spindle-related activity during NREM sleep and found that neural differentiation was not significantly correlated with spindle activity. Next, we contrasted periods of phasic REM sleep (the segments of REM sleep containing rapid eye movements) with periods of tonic REM sleep to spatially localize REM-related brain activity. Neural differentiation was most strongly, though not significantly, correlated with REM activity localized to the superior frontal gyrus, though our REM pipeline needs to be re-evaluated. We also investigated if the relationship between NREM spindle activity and neural differentiation required a subsequent period of REM sleep. We examined the correlation of spindles and neural differentiation in two experimental nap groups, a NREM sleep only group and a NREM+REM sleep group. A number of small areas had a significantly higher correlation in the NREM+REM nap group compared to the NREM only group, but further analyses is needed to evaluate if these results are significantly different from chance. Finally, we discussed these results in the context of how understanding basic mechanisms of memory transformation during sleep can inform hypotheses about how sleep might be related to memory impairments in disease states (e.g., Alzheimer’s disease)