Study maps five major eras of brain wiring from birth to old age, revealing the key turning points that shape how we learn, think, and age.
Category: life extension
Your body may already have a molecule that helps fight Alzheimer’s
Spermine, a small but powerful molecule in the body, helps neutralize harmful protein accumulations linked to Alzheimer’s and Parkinson’s. It encourages these misfolded proteins to gather into manageable clumps that cells can more efficiently dispose of through autophagy. Experiments in nematodes show that spermine also enhances longevity and cellular energy production. These insights open the door to targeted therapies powered by polyamines and advanced AI-driven molecular design.
Aging Scrambles Brain Proteins — And Diet Could Partly Reverse It
As we get older, our brains start to change in ways that make them increasingly vulnerable to disease – and a detailed new study of these changes points to a way some of this wear and tear might be prevented or reversed.
Researchers from the Leibniz Institute on Aging – Fritz Lipmann Institute in Germany used mass spectrometry to analyze the balance of brain proteins in both young and old mice, finding differences in a process called ubiquitylation as the animals aged.
Ubiquitylation adds chemical tags to proteins, telling the brain which of these busy molecules are past their peak and should be recycled. In older mouse brains, the ubiquitylation tags really start to pile up on certain proteins.
How a key protein helps drive healthy longevity by maintaining a precise balance
Researchers at Bar-Ilan University have discovered how the longevity-associated protein Sirt6 orchestrates a delicate molecular balancing act that protects the body from age-related decline and disease. The new findings, just published in the Proceedings of the National Academy of Sciences, reveal how Sirt6 preserves health during aging and may pave the way for therapies that promote a longer, healthier life.
Sirt6, often described as a master regulator of aging, is known for its powerful protective effects against age-related diseases such as cancer, diabetes, inflammation, and frailty. Its impact closely resembles that of calorie restriction, a dietary regimen proven in animals to extend lifespan and enhance the body’s natural repair and healing mechanisms.
Calorie restriction—eating fewer calories without malnutrition—has long been known to improve health and extend lifespan. One of its key effects is to increase the body’s production of hydrogen sulfide (H2S), a tiny gas molecule that supports wound healing, heart health, and brain function. This new study found that as we age, H2S levels naturally decline, weakening these protective benefits.
Mitochondrial DNA Acts as a “First Hit” for Antibody-Mediated TRALI
Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality, but its pathogenesis is complex and not well understood. TRALI is thought to develop under a “2-hit” model. In 80% of cases, the second hit is caused by antibodies (specifically anti-HLA class I or II or anti-human neutrophil antigen antibodies); bioactive lipids, extracellular vesicles and other storage-related transfusion products have been linked to the remainder of the TRALI cases. The first-hit, which is related to the patient’s underlying clinical condition, is less well defined. Since patients receiving intensive care are more prone to TRALI and often have elevated levels of extracellular mitochondrial DNA (mtDNA), researchers used a murine model to examine whether mitochondria, mtDNA or other damage-associated molecular patterns (DAMPs) can act as a first-hit in an antibody-dependent murine model of TRALI. Injection of purified mitochondria or mtDNA followed by a monoclonal antibody (as a second-hit) caused significantly greater lung injury with increased pulmonary edema, elevated plasma macrophage inflammatory protein-2 (MIP-2; the mouse ortholog of human IL-8), enhanced neutrophil lung infiltration, hypothermia, and respiratory distress compared to an isotype control. Researchers found that an antagonist to toll-like receptor-9 (TLR-9) attenuated many of the TRALI-like symptoms in mice suggesting that mtDNA and TLR-9 may be involved in the first-hit in some TRALI cases. Targeting mtDNA or the TLR-9 receptor may prove to be a novel therapeutic strategy to prevent the first-hit and TRALI, but further research is needed.
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An AI-Based System Has Found a Potential Longevity Drug
In a preprint published in bioRxiv, Prof. Vadim Gladyshev and a team of researchers have used an artificial intelligence-based system to discover a wide variety of potential interventions, including a drug that significantly improves biomarkers of frailty in mice.
Repurposing previous data
Previous research efforts have created a massive dataset in the form of the Gene Expression Omnibus (GEO), which contains the results of a great many experiments related to potentially disease-modifying drugs, many of which are tissue-specific [1]. These researchers refer to this dataset as a “massive missed opportunity” in aging research, because the vast majority of the experiments in the GEO were unrelated to aging and their data was never investigated in that context.
DNA transcription is a tightly choreographed event: How RNA polymerase II regulates the dance
Life’s instructions are written in DNA, but it is the enzyme RNA polymerase II (Pol II) that reads the script, transcribing RNA in eukaryotic cells and eventually giving rise to proteins. Scientists know that Pol II must advance down the gene in perfect sync with other biological processes; aberrations in the movement of this enzyme have been linked to cancer and aging. But technical hurdles prevented them from precisely determining how this important molecular machine moves along DNA, and what governs its pauses and accelerations.
A new study fills in many of those knowledge gaps. In a paper published in Nature Structural & Molecular Biology, researchers used a single-molecule platform to watch individual mammalian transcription complexes in action. The result is a clear view of how this molecular engine accelerates, pauses, and shifts gears as it transcribes genetic information.
“What’s really striking is how this machine functions almost like a finely tuned automobile,” says Shixin Liu, head of the Laboratory of Nanoscale Biophysics and Biochemistry. “It has the equivalent of multiple gears, or speed modes, each controlled by the binding of different regulatory proteins. We figured out, for the first time, how each gear is controlled.”