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Cognitive Stimulants: from Caffeine to Cannabinoids — Current and Future Perspectives

Habitual coffee consumers justify their life choices by arguing that they become more alert and increase motor and cognitive performance and efficiency; however, these subjective impressions still do not have a neurobiological correlation. Using functional connectivity approaches to study resting-state fMRI data in a group of habitual coffee drinkers, we herein show that coffee consumption decreased connectivity of the posterior default mode network (DMN) and between the somatosensory/motor networks and the prefrontal cortex, while the connectivity in nodes of the higher visual and the right executive control network (RECN) is increased after drinking coffee; data also show that caffeine intake only replicated the impact of coffee on the posterior DMN, thus disentangling the neurochemical effects of caffeine from the experience of having a coffee.

There is a common expectation, namely among habitual coffee drinkers, that coffee increases alertness and psychomotor functioning. For these reasons, many individuals keep drinking coffee to counteract fatigue, stay alert, increase cognitive performance, and increase work efficiency (Smith, 2002). Coffee beverages are constituted of numerous compounds known to affect human behavior, among which are caffeine and chlorogenic acids (Sadiq Butt et al., 2011). From the neurobiological perspective, both caffeine and chlorogenic acids have well-documented psychoactive actions, whereas caffeine is mostly an antagonist of the main adenosine receptors in the brain—A1 and A2A receptors, leading to the disinhibition of excitatory neurotransmitter release and enhancement of dopamine transmission via D2 receptors (Fredholm et al., 2005) to sharpen brain metabolism and bolster memory performance (Paiva et al.

357 ‒ A new era of longevity science: models of aging, rapamycin trials, biological clocks, & more

Brian Kennedy is a renowned biologist, leader in aging research, & director of the Center for Healthy Longevity at the National University of Singapore. In this episode, Brian shares insights from ongoing human aging studies, including clinical trials of rapamycin & how dosing strategies, timing, & exercise may influence outcomes. He presents two key models of aging—one as a linear accumulation of biological decline & the other as an exponential rise in mortality risk—& explains why traditional models of aging fall short. He also explains why most current aging biomarkers lack clinical utility & describes how his team is working to develop a more actionable biological clock. Additional topics include the potential of compounds like alpha-ketoglutarate, urolithin A, & NAD boosters, along with how lifestyle interventions—such as VO2 max training, strength building, & the use of GLP-1 & SGLT2 drugs—may contribute to longer, healthier lives.

View show notes here: https://bit.ly/44ShpRB
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0:00:00-Intro.
0:01:15-Brian’s journey from the Buck Institute to Singapore, & the global evolution of aging research.
0:09:12-Rethinking the biology of aging.
0:14:13-How inflammation & mTOR signaling may play a central, causal role in aging.
0:18:00-Biological role of mTOR in aging, & the potential of rapamycin to slow aging & enhance immune resilience.
0:23:32-Aging as a linear decline in resilience overlaid with non-linear health fluctuations.
0:36:03-Speculating on the future of longevity: slowing biological aging through noise reduction & reprogramming.
0:42:18-The role of the epigenome in aging, & the limits of methylation clocks.
0:47:14-Balancing the quest for immortality with the urgent need to improve late-life healthspan.
0:52:16-Comparing the big 4 chronic diseases: which are the most inevitable & modifiable?
0:57:27-Exploring potential benefits of rapamycin: how Brian is testing this & other interventions in humans.
1:09:14-Testing alpha-ketoglutarate (AKG) for healthspan benefits in aging [1:01:45];
1:13:41-Exploring urolithin A’s potential to enhance mitochondrial health, reduce frailty, & slow aging.
1:17:35-Potential of sublingual NAD for longevity.
1:26:50-Other interventions that may promote longevity: spermidine, 17 HRT, & more.
1:34:33-Biological aging clocks, clinical biomarkers, & a new path to proactive longevity care.
1:45:01-Evaluating rapamycin, metformin, & GLP-1s for longevity in healthy individuals.
1:51:19-Why muscle, strength, & fitness are the strongest predictors of healthspan.
1:53:37-Why combining too many longevity interventions may backfire.
1:56:06-How AI integration could accelerate breakthroughs in aging research.
2:02:07-Need to balance innovation with safety in longevity clinics.
2:10:50-Peter’s reflections on emerging interventions & the promise of combining proven aging compounds.

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About:

The Peter Attia Drive is a deep-dive podcast focusing on maximizing longevity, & all that goes into that from physical to cognitive to emotional health. With over 90 million episodes downloaded, it features topics including exercise, nutritional biochemistry, cardiovascular disease, Alzheimer’s disease, cancer, mental health, & much more.

Peter Attia is the founder of Early Medical, a medical practice that applies the principles of Medicine 3.0 to patients with the goal of lengthening their lifespan & simultaneously improving their healthspan.

Sensing with 2D Materials

After the successful separation of a monolayer of carbon atoms with honeycomb lattice known as graphene in 2004, a large group of 2D materials known as TMDCs and MXenes were discovered and studied. The realm of 2D materials and their heterostructures has created new opportunities for the development of various types of advanced rigid, flexible and stretchable biosensors, and chemical, optoelectronic and electrical sensors due to their unique and versatile electrical, chemical, mechanical and optical properties. The high surface to volume ratio and quantum confinement in 2D materials make them strong candidates for the development of sensors with improved sensitivity and performance. This group of atomically thin material also offer mechanical flexibility and limited stretchability harvested towards making flexible and stretchable sensors that can be used at the interface with soft tissues and in soft robotics. However, challenges remain in fully realizing their potential in practical applications.

The aim of this collection is to highlight the current progress in the research of 2D materials, focusing on their integration into sensing technologies. We seek to provide a comprehensive overview of the advancements made in this area while addressing the challenges faced in developing practical applications.

Characterization of the antibacterial activity of Bald’s eyesalve against drug resistant Staphylococcus aureus and Pseudomonas aeruginosa

In this study, we have shown that Bald’s eyesalve, an Anglo-Saxon remedy for eye sty infections, displays growth inhibitory activity against S. aureus and P. aeruginosa, including a multi-drug resistant strain. This activity was more pronounced against S. aureus than P. aeruginosa, which is consistent with the fact that Gram-negative bacteria, particularly Pseudomonads, are notably more resistant to antibacterial agents than Gram-positive bacteria, including Staphylococcus sp. [12]. Our data indicate that the specific formulation composition had little impact on the inhibition of S. aureus. This is inconsistent with a previous report where the presence of an additional Allium species, onion or leek, was found to significantly contribute to the antibacterial activity of Bald’s eyesalve [6]; however, this previous study evaluated the antibacterial activity using a synthetic wound model in which S. aureus inoculum was grown as a biofilm for 24 hr prior to treatment and based upon colony-forming units [6]. Our conflicting results may be due to our assessment of the antibacterial activity of Bald’s eyesalve exclusively against planktonic S. aureus rather than S. aureus biofilms, and we did not investigate whether onion or leek are necessary for specific efficacy against bacterial biofilms. Previous studies have shown that quercetin, an antibacterial flavonoid found in onion [13], and its derivatives demonstrate anti-biofilm and anti-quorum sensing activity against S. aureus and P. aeruginosa [14, 15]. Although plant extracts have been shown to display growth inhibitory activity against P. aeruginosa [16, 17], to our knowledge our study represents the first report of the antibacterial efficacy of Bald’s eyesalve against P. aeruginosa.

Although all known Allium species contain organosulfur compounds, the chemical composition and resultant antibacterial activity of their extracts greatly varies [18]. Prior investigations have determined the main constituents of garlic essential oil to be diallyl disulfide (DADS), diallyl trisulfide (DATS), allyl methyl trisulfide, diallyl sulfide (DAS), and diallyl tetrasulfide (DATTS), while the main constituents of onion and leek essential oils were found to be dipropyl disulfide, dipropyl trisulfide, methyl propyl disulfide, methyl propyl trisulfide, and 1-propenyl propyl disulfide [18, 19]. Tsao et al. previously demonstrated that DAS, DADS, DATS, and DATTS exhibit MICs of 20, 4, 2, and 0.5 μg/ml against S. aureus, respectively, and 80, 64, 32, and 12 μg/ml against P. aeruginosa, respectively [20, 21].

Deep life’s survival secret: Crustal faulting generates key energy sources, study shows

Chinese researchers have recently challenged the long-held belief that “all life depends on sunlight.” In a study published in Science Advances, the researchers identified how microbes in deep subsurface areas can derive energy from chemical reactions driven by crustal faulting, offering critical insights into life deep below Earth’s surface.

How a triatomic molecule works off excess energy

A resonance effect can significantly affect how a three-atom molecule cools down when excited, RIKEN physicists have found. The study, published in Physical Review A, highlights the complexity of the relaxation dynamics of even simple molecules.

Small, energetic molecules in a vacuum—such as those in the upper atmosphere or —can either break apart or cool down by releasing their energy through emitting light.

“The energy-dissipation mechanism of molecules via is crucial to understanding the stability of hot, excited molecules,” says Toshiyuki Azuma of the RIKEN Atomic, Molecular & Optical Physics Laboratory. “It’s essential in in dilute environments such as Earth’s .”

Scientists repurpose old solar panels to convert CO₂ exhaust into valuable chemicals

Centuries ago, alchemists worked furiously to convert the common metal lead to valuable gold. Today, chemists are repurposing discarded solar panels to create valuable organic compounds from carbon dioxide (CO2), a common greenhouse gas.

Significantly reducing greenhouse gases in the atmosphere to mitigate the most devastating effects of climate change will require a large reduction in emissions as well as strategies designed to sequester emitted CO2 and other offending gases. While simply sequestering greenhouse gases would fulfill this goal, creating useful organic chemicals from waste CO2 is akin to generating valuable materials from trash.

A team of chemists from Yokohama National University, Electric Power Development Co., Ltd. and the Renewable Energy Research Center at the National Institute of Advanced Industrial Science and Technology (AIST) recently decided to tackle two waste problems—excess CO2 emissions and decommissioned —in the pursuit of creating value-added organic chemicals. The team designed a study to determine if recycled components of discarded solar panels could be used to efficiently convert CO2 into useful, carbon-based compounds.

A Complete Human Genome Built from Scratch: This Unprecedented Scientific Feat Could Transform Everything We Know About Biology

IN A NUTSHELL 🌐 The SynHG project aims to synthesize a complete human genome, opening new horizons in biotechnology. ⚖️ Ethical considerations are central to the project, with a focus on responsible innovation and diverse cultural perspectives. 🧬 Initial steps involve creating a fully synthetic human chromosome, leveraging advances in synthetic biology and DNA chemistry.