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136
Date Added: Dec 1, 2021
Date Added: Dec 1, 2021
The search continues for possible interventions that delay and/or reverse biological aging, resulting in extended healthspan and lifespan. Interventions delaying aging in animal models are well established; however, most lack validation in humans. The length of human lifespan makes it impractical to perform survival analysis. Instead, aging biomarkers, such as DNA methylation (DNAm) clocks, have been developed to monitor biological age. Herein we report a retrospective analysis of DNA methylation age in 42 individuals taking Rejuvant®, an alpha-ketoglutarate based formulation, for an average period of 7 months. DNAm testing was performed at baseline and by the end of treatment with Rejuvant® supplementation. Remarkably, individuals showed an average decrease in biological aging of 8 years (p-value=6.538x10-12). Furthermore, the supplementation with Rejuvant® is robust to individual differences, as indicated by the fact that a large majority of participants decreased their biological age. Moreover, we found that Rejuvant® is of additional benefit to chronologically and biologically older individuals. While continued testing, particularly in a placebo-controlled design, is required, the nearly 8-year reversal in the biological age of individuals taking Rejuvant® for 4 to 10 months is noteworthy, making the natural product cocktail an intriguing candidate to affect human aging.
11
Date Added: Nov 27, 2021
Date Added: Nov 27, 2021
Hippocampal function is critical for spatial and contextual learning, and its decline with age contributes to cognitive impairment. Exercise can improve hippocampal function, however, the amount of exercise and mechanisms mediating improvement remain largely unknown. Here, we show exercise reverses learning deficits in aged (24 months) female mice but only when it occurs for a specific duration, with longer or shorter periods proving ineffective. A spike in the levels of growth hormone (GH) and a corresponding increase in neurogenesis during this sweet spot mediate this effect because blocking GH receptor with a competitive antagonist or depleting newborn neurons abrogates the exercise-induced cognitive improvement. Moreover, raising GH levels with GH-releasing hormone agonist improved cognition in nonrunners. We show that GH stimulates neural precursors directly, indicating the link between raised GH and neurogenesis is the basis for the substantially improved learning in aged animals.
9
Date Added: Nov 29, 2021
Date Added: Nov 29, 2021
The brain is the seat of body weight homeostasis. However, our inability to control the increasing prevalence of obesity highlights a need to look beyond canonical feeding pathways to broaden our understanding of body weight control. Here we used a reverse-translational approach to identify and anatomically, molecularly and functionally characterize a neural ensemble that promotes satiation. Unbiased, task-based functional magnetic resonance imaging revealed marked differences in cerebellar responses to food in people with a genetic disorder characterized by insatiable appetite. Transcriptomic analyses in mice revealed molecularly and topographically -distinct neurons in the anterior deep cerebellar nuclei (aDCN) that are activated by feeding or nutrient infusion in the gut. Selective activation of aDCN neurons substantially decreased food intake by reducing meal size without compensatory changes to metabolic rate. We found that aDCN activity terminates food intake by increasing striatal dopamine levels and attenuating the phasic dopamine response to subsequent food consumption. Our study defines a conserved satiation centre that may represent a novel therapeutic target for the management of excessive eating, and underscores the utility of a ‘bedside-to-bench’ approach for the identification of neural circuits that influence behaviour.
5
Date Added: Nov 29, 2021
Date Added: Nov 29, 2021
When we remember a city that we have visited, we retrieve places related to finding our goal but also non-target locations within this environment. Yet, understanding how the human brain implements the neural computations underlying holistic retrieval remains unsolved, particularly for shared aspects of environments. Here, human participants learned and retrieved details from three partially overlapping environments while undergoing high-resolution functional magnetic resonance imaging (fMRI). Our findings show reinstatement of stores even when they are not related to a specific trial probe, providing evidence for holistic environmental retrieval. For stores shared between cities, we find evidence for pattern separation (representational orthogonalization) in hippocampal subfield CA2/3/DG and repulsion in CA1 (differentiation beyond orthogonalization). Additionally, our findings demonstrate that medial prefrontal cortex (mPFC) stores representations of the common spatial structure, termed schema, across environments. Together, our findings suggest how unique and common elements of multiple spatial environments are accessed computationally and neurally.
8
Date Added: Nov 7, 2021
Date Added: Nov 7, 2021
Here we demonstrate a more effective use of III–V photoconversion material to achieve an ultrahigh power-per-weight ratio from a solar cell utilizing an axial p-i-n junction GaAs/AlGaAs nanowire (NW) array grown by molecular beam epitaxy on a Si substrate. By analyzing single NW multicontact devices, we first show that an n-GaAs shell is self-formed radially outside the axial p- and i-core of the GaAs NW during n-core growth, which significantly deteriorates the rectification property of the NWs in the axial direction. When employing a selective-area ex situ etching process for the n-GaAs shell, a clear rectification of the axial NW p-i-n junction with a high on/off ratio was revealed. Such a controlled etching process of the self-formed n-GaAs shell was further introduced to fabricate axial p-i-n junction GaAs NW array solar cells. Employing this method, a GaAs NW array solar cell with only ∼1.3% areal coverage of the NWs shows a photoconversion efficiency of ∼7.7% under 1 Sun intensity (AM 1.5G), which is the highest achieved efficiency from any single junction GaAs NW solar cell grown on a Si substrate so far. This corresponds to a power-per-weight ratio of the active III–V photoconversion material as high as 560 W/g, showing great promise for high-efficiency and low-cost III–V NW solar cells and III–V NW/Si tandem solar cells.
186
Date Added: Nov 27, 2021
Date Added: Nov 27, 2021
Caloric restriction has been known for nearly a century to extend life span and delay age-associated pathology in laboratory animals. More recently, alternative “antiaging” diet modalities have been described that provide new mechanistic insights and potential clinical applications. These include intermittent fasting, fasting-mimicking diets, ketogenic diets, time-restricted feeding, protein restriction, and dietary restriction of specific amino acids. Despite mainstream popularization of some of these diets, many questions remain about their efficacy outside of a laboratory setting. Studies of these interventions support at least partially overlapping mechanisms of action and provide insights into what appear to be highly conserved mechanisms of biological aging.
7
Date Added: Nov 7, 2021
Date Added: Nov 7, 2021
Increased levels of peripheral cytokines have been previously associated with depression in preclinical and clinical research. Although the precise nature of peripheral immune dysfunction in depression remains unclear, evidence from animal studies points towards a dysregulated response of peripheral leukocytes as a risk factor for stress susceptibility. This study examined dynamic release of inflammatory blood factors from peripheral blood mononuclear cells (PBMC) in depressed patients and associations with neural and behavioral measures of reward processing. Thirty unmedicated patients meeting criteria for unipolar depressive disorder and 21 healthy control volunteers were enrolled. PBMCs were isolated from whole blood and stimulated ex vivo with lipopolysaccharide (LPS). Olink multiplex assay was used to analyze a large panel of inflammatory proteins. Participants completed functional magnetic resonance imaging with an incentive flanker task to probe neural responses to reward anticipation, as well as clinical measures of anhedonia and pleasure including the Temporal Experience of Pleasure Scale (TEPS) and the Snaith-Hamilton Pleasure Scale (SHAPS). LPS stimulation revealed larger increases in immune factors in depressed compared to healthy subjects using an aggregate immune score (t49 = 2.83, p = 0.007). Higher peripheral immune score was associated with reduced neural responses to reward anticipation within the ventral striatum (VS) (r = −0.39, p = 0.01), and with reduced anticipation of pleasure as measured with the TEPS anticipatory sub-score (r = −0.318, p = 0.023). Our study provides new evidence suggesting that dynamic hyper-reactivity of peripheral leukocytes in depressed patients is associated with blunted activation of the brain reward system and lower subjective anticipation of pleasure.
2
Date Added: Nov 24, 2021
Date Added: Nov 24, 2021
The age spectrum of human populations is shifting toward the older with larger proportions suffering physical decline. Mitochondria influence the pace of aging as the energy they provide for cellular function in the form of adenosine triphosphate (ATP) declines with age. Mitochondrial density is greatest in photoreceptors, particularly cones that have high energy demands and mediate color vision. Hence, the retina ages faster than other organs, with a 70% ATP reduction over life and a significant decline in photoreceptor function. Mitochondria have specific light absorbance characteristics influencing their performance. Longer wavelengths spanning 650–>1,000 nm improve mitochondrial complex activity, membrane potential, and ATP production. Here, we use 670-nm light to improve photoreceptor performance and measure this psychophysically in those aged 28–72 years. Rod and cone performance declined significantly after approximately 40 years of age. 670-nm light had no impact in younger individuals, but in those around 40 years and older, significant improvements were obtained in color contrast sensitivity for the blue visual axis (tritan) known to display mitochondrial vulnerability. The red visual axis (protan) improved but not significantly. Rod thresholds also improved significantly in those >40 years. Using specific wavelengths to enhance mitochondrial performance will be significant in moderating the aging process in this metabolically demanding tissue.
127
Date Added: Nov 18, 2021
Date Added: Nov 18, 2021
Self-objectification, the internalization of an observer’s appearance-based perspective of one’s body, has been theorized and demonstrated to reduce body awareness among women. In this field study, we propose self-objectification as the mechanism to explain the oft-observed phenomenon where women wearing little clothing appear unbothered by cold weather, positing that self-objectification obstructs women’s feelings of cold. We surveyed women outside nightclubs on cold nights, assessed self-objectification, and asked participants to report how cold they felt. Anonymous photos were taken and coded for amount of skin exposure. We hypothesized that self-objectification would moderate the relationship between clothing coverage and reports of feeling cold. Our hypothesis was supported: women low in self-objectification showed a positive, intuitive, relationship between skin exposure and perceptions of coldness, but women more highly focused on their appearance did not feel colder when wearing less clothing. These findings offer support for the relationship between self-objectification and awareness of bodily sensations in the context of a naturalistic setting. We discuss implications of these findings, and also consider limitations, an alternative explanation, and directions for future research.