One protein may decide whether brain chemistry heals or harms

Tryptophan is widely known for its connection to sleep, but its importance goes much further. The compounds produced from tryptophan help build proteins, generate cellular energy (NAD+), and create essential brain chemicals such as serotonin and melatonin. Together, these processes support mood, learning, and healthy sleep patterns.

As the brain ages or develops neurological disease, this system begins to break down. Scientists have repeatedly observed disruptions in how tryptophan is processed in aging brains, with even stronger effects seen in neurodegenerative and psychiatric disorders. These changes are linked to worsening mood, impaired learning, and disturbed sleep. Until now, however, researchers did not know what caused the brain to shift how it uses tryptophan in the first place.

SIRT6 Identified as a Key Regulator of Brain Chemistry

Prof. Debra Toiber and her research team at Ben-Gurion University of the Negev have now uncovered a clear biological explanation. Their work points to the loss of a longevity-related protein called Sirtuin 6 (SIRT6) as the driving factor behind this metabolic imbalance.

Using experiments in cells, Drosophila (fly), and mouse models, the researchers showed that SIRT6 plays an active role in controlling gene expression (e.g., TDO2, AANAT). When SIRT6 levels drop, this control is lost. As a result, tryptophan is redirected toward the kynurenic pathway, which produces neurotoxic compounds, while the production of protective neurotransmitters such as serotonin and melatonin declines.

Published Evidence and a Reversible Effect

The findings were recently published in Nature Communications.

Importantly, the researchers also found that the damage caused by this shift is not permanent. In a SIRT6 knockout fly model, blocking the enzyme TDO2 led to a significant improvement in movement problems and reduced the formation of vacuoles, which are signs of brain tissue damage. These results suggest that there may be a meaningful window for therapeutic intervention.

"Our research positions SIRT6 as a critical, upstream drug target for combating neurodegenerative pathology," says Prof. Toiber.

Research Team and Funding Support

Additional researchers include: Shai Kaluski-Kopatch, Daniel Stein, Alfredo Garcia Venzor, Ana Margarida Ferreira Campos, Melanie Planque, Bareket Goldstein, Estefanía De Allende-Becerra, Dmitrii Smirnov, Adam Zaretsky, Dr Ekaterina Eremenko -- Sgibnev, Miguel Portillo, Monica Einav, Alena Bruce Krejci, Uri Abdu, Ekaterina Khrameeva, Daniel Gitler, and Sarah-Maria Fendt.

The study was supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 849029), the David and Inez Myers foundation, the Israeli Ministry of Science and Technology (MOST), the High-tech, Bio-tech and Negev fellowships of Kreitman School of Advanced Research of Ben-Gurion University and The Israel Science Foundation (Grant no. 422/23). The RNA-seq data analysis was supported by the Russian Science Foundation (grant number 25-71-20017). 

 

Journal Reference:

1. Shai Kaluski-Kopatch, Daniel Stein, Alfredo Garcia Venzor, Ana Margarida Ferreira Campos, Melanie Planque, Bareket Goldstein, Estefanía De Allende-Becerra, Dmitrii Smirnov, Adam Zaretsky, Ekaterina Eremenko, Miguel Portillo, Monica Einav, Alena Bruce Krejci, Uri Abdu, Ekaterina Khrameeva, Daniel Gitler, Sarah-Maria Fendt, Debra Toiber. Histone deacetylase SIRT6 regulates tryptophan catabolism and prevents metabolite imbalance associated with neurodegeneration. Nature Communications, 2025; 17 (1) DOI: 10.1038/s41467-025-67021-y 

Courtesy:

Ben-Gurion University of the Negev. "One protein may decide whether brain chemistry heals or harms." ScienceDaily. ScienceDaily, 15 January 2026. <www.sciencedaily.com/releases/2026/01/260115022811.htm>. 

Statins may help almost everyone with type 2 diabetes live longer

 

A large long-term study has found that statins, a widely used class of cholesterol-lowering medications, significantly reduce the risk of death and serious heart-related problems in adults with type 2 diabetes. Importantly, these benefits were seen even in people who were considered to have a low chance of developing heart disease within the next 10 years. This challenges a long-standing debate over whether preventive statin treatment is worthwhile for patients who appear to be at lower cardiovascular risk.

Statins are commonly prescribed to lower LDL cholesterol, what many people know as bad cholesterol. High LDL levels are linked to clogged arteries, heart attacks, and strokes. People with type 2 diabetes already face a higher risk of cardiovascular disease, but doctors have not always agreed on whether statins are necessary for those whose short-term heart risk appears minimal. The new findings suggest that statins may offer protective effects for a much wider group of diabetes patients than previously believed. The study was published in Annals of Internal Medicine.

The research team, led by scientists from the University of Hong Kong, examined health records from the IQVIA Medical Research Data (IMRD)-UK database. Their goal was to assess both the effectiveness and safety of starting statin therapy for primary prevention. Primary prevention refers to preventing a first heart attack or stroke before any such event has occurred.

The study focused on adults in the United Kingdom with type 2 diabetes between the ages of 25 and 84. Participants were followed for as long as 10 years. At the start of the study, none of the individuals had serious heart disease or significant liver problems, allowing researchers to more clearly assess the effects of statins without interference from existing severe conditions.

Statins Reduced Death and Heart Events at Every Risk Level

Researchers compared people who began taking statins with those who did not, grouping them based on their predicted 10-year risk of developing cardiovascular disease. This risk estimate is commonly used in clinical practice to guide treatment decisions.

Across all risk categories, statin use was linked to lower rates of death from any cause and fewer major cardiovascular events such as heart attacks and strokes. Even participants classified as low risk experienced measurable benefits, which directly challenges the assumption that statins only help people already at high risk of heart disease.

Safety Findings and What They Mean for Patients

In terms of safety, the researchers observed a very small increase in myopathy in one risk group. Myopathy refers to muscle-related side effects, which can include weakness or soreness and are a known but uncommon concern with statin use. No increase in liver-related problems was found, addressing another common worry among patients and clinicians.

Based on these results, the authors concluded that doctors should carefully consider the advantages of statin therapy for all adults with type 2 diabetes, even when a person's short-term predicted risk of cardiovascular disease is low. The findings suggest that relying solely on short-term risk estimates may cause some patients to miss out on treatments that could help them live longer and avoid serious heart complications.

Journal Reference:

1. Vincent Ka Chun Yan, Joseph Edgar Blais, John-Michael Gamble, Esther Wai Yin Chan, Ian Chi Kei Wong, Eric Yuk Fai Wan. Effectiveness and Safety of Statins in Type 2 Diabetes According to Baseline Cardiovascular Risk. Annals of Internal Medicine, 2025; DOI: 10.7326/ANNALS-25-00662 

Courtesy:

American College of Physicians. "Statins may help almost everyone with type 2 diabetes live longer." ScienceDaily. ScienceDaily, 15 January 2026. <www.sciencedaily.com/releases/2026/01/260115022812.htm>.