Curcuma longa L. Prevents the Loss of β-Tubulin in the Brain and Maintains Healthy Aging in Drosophila melanogaster

Loss of tubulin is associated with neurodegeneration and brain aging. Turmeric (Curcuma longa L.) has frequently been employed as a spice in curry and traditional medications in the Indian subcontinent to attain longevity and better cognitive performance. We aimed to evaluate the unelucidated mechanism of how turmeric protects the brain to be an anti-aging agent. D. melanogaster was cultured on a regular diet and turmeric-supplemented diet. β-tubulin level and physiological traits including survivability, locomotor activity, fertility, tolerance to oxidative stress, and eye health were analyzed. Turmeric showed a hormetic effect, and 0.5% turmeric was the optimal dose in preventing aging. β-tubulin protein level was decreased in the brain of D. melanogaster upon aging, while a 0.5% turmeric-supplemented diet predominantly prevented this aging-induced loss of β-tubulin and degeneration of physiological traits as well as improved β-tubulin synthesis in the brain of D. melanogaster early to mid-age. The higher concentration (≥ 1%) of turmeric-supplemented diet decreased the β-tubulin level and degenerated many of the physiological traits of D. melanogaster. The turmeric concentration-dependent increase and decrease of β-tubulin level were consistent with the increment and decrement data obtained from the evaluated physiological traits. This correlation demonstrated that turmeric targets β-tubulin and has both beneficial and detrimental effects that depend on the concentration of turmeric. The findings of this study concluded that an optimal dosage of turmeric could maintain a healthy neuron and thus healthy aging, by preventing the loss and increasing the level of β-tubulin in the brain.

Independent morphological variables correlate with Aging, Mild Cognitive Impairment, and Alzheimer's Disease

This manuscript presents a study with recruited volunteers that comprehends three sorts of events present in Alzheimer's Disease (AD) evolution (structural, biochemical, and cognitive) to propose an update in neurodegeneration biomarkers for AD. The novel variables, K, I, and S, suggested based on physics properties and empirical evidence, are defined by power-law relations between cortical thickness, exposed and total area, and natural descriptors of brain morphology. Our central hypothesis is that variable K, almost constant in healthy human subjects, is a better discriminator of a diseased brain than the current morphological biomarker, Cortical Thickness, due to its aggregated information. We extracted morphological features from 3T MRI T1w images of 123 elderly subjects: 77 Healthy Cognitive Unimpaired Controls (CTL), 33 Mild Cognitive Impairment (MCI) patients, and 13 Alzheimer's Disease (AD) patients. Moreover, Cerebrospinal Fluid (CSF) biomarkers and clinical data scores were correlated with K, intending to characterize health and disease in the cortex with morphological criteria and cognitive-behavioral profiles. K distinguishes Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Cognitive Unimpaired Controls globally and locally with reasonable accuracy (CTL-AD, 0.82; CTL-MCI, 0.58). Correlations were found between global and local K associated with clinical behavioral data (executive function and memory assessments) and CSF biomarkers (t-Tau, Aβ-40, and Aβ-42). The results suggest that the cortical folding component, K, is a premature discriminator of healthy aging, Mild Cognitive Impairment, and Alzheimer's Disease, with significant differences within diagnostics. Despite the non-concomitant events, we found correlations between brain structural degeneration (K), cognitive tasks, and biochemical markers.

From the Heart to the Brain: Building Bridges to a Better Future

This Presidential Address was delivered at the International Stroke Conference in March 2021, during the coronavirus pandemic. Dr Elkind, the President of the American Heart Association (AHA) at the time, is a vascular neurologist with a research focus on stroke epidemiology. This address interweaves personal reflections on a career in clinical neurology, stroke research, and public health with a discussion of the role of the AHA in improving cardiovascular health at multiple levels. Throughout its history, the AHA has had leaders representing many different areas of cardiovascular science and medicine, including stroke. More recently, its focus has expanded from a traditional emphasis on cardiovascular events illness and events, like heart disease and stroke, to an appreciation of the role of the vascular system in brain health, healthy aging, cognitive decline, and dementia. During the pandemic, as the bidirectional effects of the coronavirus on cardiovascular disease has been elucidated, the benefits of a broad and multidisciplinary approach to cardiovascular disease and public health have become more apparent than ever. In addition, with growing awareness of the disproportionate effects of the pandemic on communities of color in the United States and globally, the AHA has redoubled its focus on addressing the social determinants of health, including structural racism. Central to these efforts is the construction of bridges between the generation of scientific knowledge and action for the public good. Our success will depend on the combination of basic, translational, clinical and population research with programs of public and professional education, advocacy, and social action.

Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans

Metabolic stress due to nutrient excess and lipid accumulation is at the root of many age-associated disorders and the identification of therapeutic targets that mimic the beneficial effects of calorie restriction has clinical importance. Here, using C. elegans as a model organism, we study the roles of a recently discovered enzyme at the heart of metabolism in mammalian cells, glycerol-3-phosphate phosphatase (G3PP) (gene name Pgp) that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol. We identify three Pgp homologues in C. elegans (pgph) and demonstrate in vivo that their protein products have G3PP activity, essential for glycerol synthesis. We demonstrate that PGPH/G3PP regulates the adaptation to various stresses, in particular hyperosmolarity and glucotoxicity. Enhanced G3PP activity reduces fat accumulation, promotes healthy aging and acts as a calorie restriction mimetic at normal food intake without altering fertility. Thus, PGP/G3PP can be considered as a target for age-related metabolic disorders.

The forest, the trees, and the leaves across adulthood: Age-related changes on a visual search task containing three-level hierarchical stimuli

Selecting relevant visual information in complex scenes by processing either global information or local parts helps us act efficiently within our environment and achieve goals. A global advantage (faster global than local processing) and global interference (global processing interferes with local processing) comprise an evidentiary global precedence phenomenon in early adulthood. However, the impact of healthy aging on this phenomenon remains unclear. As such, we collected behavioral data during a visual search task, including three-levels hierarchical stimuli (i.e., global, intermediate, and local levels) with several hierarchical distractors, in 50 healthy adults (26 younger (mean age: 26 years) and 24 older (mean age: 62 years)). Results revealed that processing information presented at the global and intermediate levels was independent of age. Conversely, older adults were slower for local processing compared to the younger adults, suggesting lower efficiency to deal with visual distractors during detail-oriented visual search. Although healthy older adults continued exhibiting a global precedence phenomenon, they were disproportionately less efficient during local aspects of information processing, especially when multiple visual information was displayed. Our results could have important implications for many life situations by suggesting that visual information processing is impacted by healthy aging, even with similar visual stimuli objectively presented.

The Effects of Healthy Aging on Right Ventricular Structure and Biomechanical Properties: A Pilot Study

Healthy aging has been associated with alterations in pulmonary vascular and right ventricular (RV) hemodynamics, potentially leading to RV remodeling. Despite the current evidence suggesting an association between aging and alterations in RV function and higher prevalence of pulmonary hypertension in the elderly, limited data exist on age-related differences in RV structure and biomechanics. In this work, we report our preliminary findings on the effects of healthy aging on RV structure, function, and biomechanical properties. Hemodynamic measurements, biaxial mechanical testing, constitutive modeling, and quantitative transmural histological analysis were employed to study two groups of male Sprague-Dawley rats: control (11 weeks) and aging (80 weeks). Aging was associated with increases in RV peak pressures (+17%, p = 0.017), RV contractility (+52%, p = 0.004), and RV wall thickness (+38%, p = 0.001). Longitudinal realignment of RV collagen (16.4°, p = 0.013) and myofibers (14.6°, p = 0.017) were observed with aging, accompanied by transmural cardiomyocyte loss and fibrosis. Aging led to increased RV myofiber stiffness (+141%, p = 0.003), in addition to a bimodal alteration in the biaxial biomechanical properties of the RV free wall, resulting in increased tissue-level stiffness in the low-strain region, while progressing into decreased stiffness at higher strains. Our results demonstrate that healthy aging may modulate RV remodeling via increased peak pressures, cardiomyocyte loss, fibrosis, fiber reorientation, and altered mechanical properties in male Sprague-Dawley rats. Similarities were observed between aging-induced remodeling patterns and those of RV remodeling in pressure overload. These findings may help our understanding of age-related changes in the cardiovascular fitness and response to disease.

Consciousness Beyond Neural Fields: Expanding the Possibilities of What Has Not Yet Happened

In the field theories in physics, any particular region of the presumed space-time continuum and all interactions between elementary objects therein can be objectively measured and/or accounted for mathematically. Since this does not apply to any of the field theories, or any other neural theory, of consciousness, their explanatory power is limited. As discussed in detail herein, the matter is complicated further by the facts than any scientifically operational definition of consciousness is inevitably partial, and that the phenomenon has no spatial dimensionality. Under the light of insights from research on meditation and expanded consciousness, chronic pain syndrome, healthy aging, and eudaimonic well-being, we may conceive consciousness as a source of potential energy that has no clearly defined spatial dimensionality, but can produce significant changes in others and in the world, observable in terms of changes in time. It is argued that consciousness may have evolved to enable the human species to generate such changes in order to cope with unprecedented and/or unpredictable adversity. Such coping could, ultimately, include the conscious planning of our own extinction when survival on the planet is no longer an acceptable option.