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Inside the World’s First Age Reversal Trial | Lifespan with Dr. David Sinclair — S2, Ep. 4

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In this episode of Lifespan, Dr. David Sinclair, A.O., Ph.D. – Professor of Genetics at Harvard Medical School and pioneer in longevity research – explores the science of eye aging, vision loss, and emerging strategies to preserve vision throughout life.

Dr. Sinclair shares an inside update on ER-100, including his team’s successful restoration of vision in non-human primates and the launch of the world’s first FDA-cleared age reversal human clinical trial. This Phase 1 clinical trial will evaluate the safety of epigenetic cellular restoration as a therapy.

Additionally, drawing on decades of research, Dr. Sinclair explains why the eyes may offer one of the earliest windows into biological aging, how everyday factors such as sleep position, alcohol consumption, and intraocular pressure influence long-term eye health, and what the latest evidence reveals about nutrition, supplements, and the connection between the eyes and the brain.

Gene activity in blood fluctuates more than expected—and that has consequences for medicine

Take a blood sample from someone in the dead of winter. Take another in midsummer. Same person, same laboratory. And yet, at the level of gene activity, the molecular picture can look surprisingly different. This is not an anomaly. This, a new Nature Communications study argues, is simply how human biology works, and it has significant implications for the way biomarkers have traditionally been studied.

Researchers from Kiel University’s Excellence Cluster PMI, KU Leuven and the German Center for Neurodegenerative Diseases (DZNE) in Bonn tracked 333 volunteers in Flanders over six months, drawing blood three times and measuring the activity of roughly 14,000 genes on each occasion.

What they found suggests that an important source of biological variation has been underappreciated in many clinical studies: in 85% of all genes, the variation within a single person over time is larger than the variation between different people. In other words, for most genes, the largest differences are observed between two time points in the same individual rather than between different individuals.

Humans Can Learn to Echolocate in Just 10 Weeks, And It Rewires The Brain

Echolocation is a fascinating way that animals like bats and whales find their way around the world.

By emitting sounds and decoding the echoes that come back, these species are able to detect what’s around them in their local environment.

It’s something we know that humans can do too – and it takes less training than you might think.

Two heart nerve cell types sustain cardiac stability in mice

Researchers identified two major intrinsic cardiac neuron populations in mice: Npy-positive neurons regulate parasympathetic heart rate control and support coronary perfusion, while Ddah1-positive neurons help maintain electrical stability during extreme stress. Removing Npy-positive neurons caused fatal cardiac failure, whereas loss of Ddah1-positive neurons increased susceptibility to malignant arrhythmias and sudden cardiac arrest under stress.

Traveling waves in rat brains give hints about information transfer in consciousness

How and why we experience consciousness is a question that has long plagued philosophers and scientists alike. We have come to understand that, when awake, our brains organize neural information for perception, yet we completely lose this organization under anesthesia. Why this happens is a longstanding mystery in neuroscience, as simple changes in the activity levels of specific brain regions fail to explain this disappearance of consciousness.

Theories have hypothesized that conscious perception arises from two core pillars: the brain’s ability to encode external features and its ability to transmit information across different cortical regions. While the former has been well supported, direct physical evidence of the latter has remained elusive. A team of researchers at Kyoto University set out to bridge this critical gap between neural signals and information dynamics.

The paper is published in the journal iScience.

Three genetic modifiers may alter inherited Alzheimer’s onset and progression

Autosomal dominant Alzheimer’s disease (ADAD) is a genetically inherited form of Alzheimer’s disease that accounts for only about 1% of Alzheimer’s disease cases. However, because individuals with the gene mutations are extremely likely to develop Alzheimer’s disease at an early age, and because the mutation is highly heritable, ADAD is widely studied by Alzheimer’s disease researchers.

A new study by WashU Medicine researchers and collaborators, published in The Lancet Neurology, identified variants in three other genes that seem to change how Alzheimer’s disease presents in people with ADAD mutations. Pinpointing these and other genetic factors that affect Alzheimer’s disease development and progression may allow investigators to provide more effective genetic counseling for families, design clinical trials and develop new treatments to prevent or slow Alzheimer’s disease in the larger population.

Previous studies had already identified three key genes—amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2)—that are associated with ADAD, as well as 279 variants in those genes that lead to Alzheimer’s disease. What remains unclear, however, is what leads to differences in disease onset and progression among individuals who have a disease-causing variant. For instance, even if a person carries an APP, PSEN1 or PSEN2 mutation and is therefore very likely to develop early-onset Alzheimer’s, there is variability in when symptoms of cognitive decline might begin, even among individuals who have the same disease-causing mutation.

DMTInduced Shifts in Criticality Correlate with SelfDissolution

Psychedelics profoundly alter subjective experience and brain dynamics. Brain oscillations express signatures of near-critical dynamics, relevant for healthy function. Alterations in the proximity to criticality have been suggested to underlie the experiential and neurological effects of psychedelics. Here, we investigate the effects of a psychedelic substance (DMT) on the criticality of brain oscillations, and in relation to subjective experience, in humans of either sex. We find that DMT shifts the dynamics of brain oscillations away from criticality in alpha and adjacent frequency bands. In this context, entropy is increased while complexity is reduced. We find that the criticality-shifts observed in alpha and theta bands correlate with the intensity ratings of self-dissolution, a hallmark of psychedelic experience. Finally, using a recently developed metric, the functional excitatory-inhibitory ratio, we find that the DMT-induced criticality-shift in brain oscillations is toward subcritical regimes. These findings have major implications for the neuronal understanding of the self and psychedelics, as well as for the neurological basis of altered states of consciousness.

Keywords: DMT; EEG; brain oscillations; criticality; self-dissolution.

Copyright © 2025 Irrmischer et al.

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