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Category: genetics

New Mega-Analysis Reveals Why Memory Declines With Age

A landmark international study that pooled brain scans and memory tests from thousands of adults has shed new light on how structural brain changes are tied to memory decline as people age.

The findings — based on more than 10,000 MRI scans and over 13,000 memory assessments from 3,700 cognitively healthy adults across 13 studies — show that the connection between shrinking brain tissue and declining memory is nonlinear, stronger in older adults, and not solely driven by known Alzheimer’s-associated genes like APOE ε4. This suggests that brain aging is more complex than previously thought, and that memory vulnerability reflects broad structural changes across multiple regions, not just isolated pathology.

Published in Nature Communications, the study, “Vulnerability to memory decline in aging revealed by a mega-analysis of structural brain change,” found that structural brain change associated with memory decline is widespread, rather than confined to a single region. While the hippocampus showed the strongest association between volume loss and declining memory performance, many other cortical and subcortical regions also demonstrated significant relationships. This suggests that cognitive decline in aging reflects a distributed macrostructural brain vulnerability, rather than deterioration in a few specific brain regions. The pattern across regions formed a gradient, with the hippocampus at the high end and progressively smaller but still meaningful effects across large portions of the brain.

https://www.nature.com/articles/s41467-025-66354-y

Genetic risk for Alzheimer’s and widespread brain shrinkage linked to greater memory loss — even in otherwise healthy adults.

Three-parent babies: Mitochondrial replacement therapies

The mitochondria are membrane-bound intracellular organelles present in almost all eukaryotic cells (). They generate energy through oxidative phosphorylation, and are responsible for 90% of cellular ATP (). In mammals, the mitochondria are present in all cells, except the enucleated red blood cells, being more present in tissues that need energy metabolism, with several units of the organelle. They have a round or oval shape and are about 0.5 to 1 µm in diameter, and up to 7 µm in length (). Together with the cell nucleus, they are the only cell organelle having their own genome, an extremely compact molecule, with 16.500 base pairs and 37 genes: 13 messenger RNAs, 22 RNAs, and 2 ribosomal RNAs. The D-loop is the only non-coding region in mtDNA, since introns and intergenic regions are non-existent or restricted to a few nucleotides ().

In addition to the production of reactive oxygen species due to the release of free electrons generated from the respiratory chain, mitochondria have few repair systems and therefore are subject to genetic mutations, causing diseases that affect approximately 1 in 5,000 people (). Mitochondrial diseases can affect organs that depend on energy metabolism, such as skeletal muscle, cardiac, central nervous system, endocrine, retina and liver (; ), giving rise to several incurable diseases, such as: deafness, diabetes mellitus, myopathies, glaucoma and others (). These metabolic disorders, lead to inefficient oxidative phosphorylation, impairing cell energy production (). They are difficult to diagnose and most of the time untreated, affecting adults and children ().

Mitochondria are inherited only from the female gamete; therefore, the mitochondrial DNA is of exclusive maternal inheritance (). The genetic mutations present in this material can be avoided using mitochondrial substitution techniques (), where the nuclear genome is withdrawn from an oocyte, which carries mitochondrial mutations, and is implanted in a normal enucleated donor ().

First breathing ‘lung-on-chip’ developed using genetically identical cells

Researchers at the Francis Crick Institute and AlveoliX have developed the first human lung-on-chip model using stem cells taken from only one person. These chips simulate breathing motions and lung disease in an individual, holding promise for testing treatments for infections like tuberculosis (TB) and delivering personalized medicine.

The research is published in the journal Science Advances.

Air sacs in the lungs called alveoli are the essential site of gas exchange and also an important barrier against inhaled viruses and bacteria that cause respiratory diseases like flu or TB.

Scientists turn cells’ most mysterious structures into spies on genetic activity

The barrel-shaped structures found by the thousands in most animal cells are one of biology’s biggest mysteries. But although researchers haven’t figured out the function of these “vaults,” they now report a new use for the puzzling particles.

Enigmatic ‘vaults’ can be engineered to eavesdrop on RNA, aiding cancer studies and more.

A breakthrough in DNA sequencing hints at why most smokers don’t get lung cancer

Breakthrough in DNA sequencing offers clues to why most smokers do not develop lung cancer.

“Our data suggest that these individuals may have survived for so long in spite of their heavy smoking because they managed to suppress further mutation accumulation,” says pulmonologist and genetics researcher Simon Spivack, a co-author on the study. “This leveling off of mutations could stem from these people having very proficient systems for repairing DNA damage or detoxifying cigarette smoke.”

Researchers who study the health effects of cigarette smoke have used all kinds of methods — from giving lab animals high doses of chemicals found in tobacco to combing through archives to determine which diseases smokers get more often — to figure out how the habit affects the body. Those studies have made it clear that cigarettes contain hundreds of harmful chemicals, including dozens of carcinogens.

For decades, researchers didn’t have any way to measure the mutations in lung cells that actually cause lung cancer. Five years ago, researchers at Albert Einstein College of Medicine in New York found a way to overcome technical limitations that had made it impossible to sequence the genome. That is, they figured out how to determine the exact order of the A, T, C, and G molecules of the DNA within a single cell without introducing too many errors in the process.

A Genetic Risk Adoption Design for Psychiatric and Substance Use Disorders

Paternal genetic risk is a robust predictor of offspring psychiatric disorders, with additional “indirect genetic effects” observed for internalizing and substance use conditions in adoptive and stepfather relationships. Rearing effects were most pronounced for substance use disorders.

Question In an adoption study of major psychiatric illness, what results would be obtained if offspring risk were predicted not from the phenotype of the parents but from their genetic risk?

Findings In this cohort study, paternal genetic risk was associated with offspring risk of illness for all disorders in genetically related father-offspring pairs. In an indirect pathway, genetic risk in adoptive and stepfathers predicted risk in their offspring for internalizing and substance use disorders but not for schizophrenia or bipolar disorder.

Meaning Indirect genetic effects from the father may have an impact on offspring risk of internalizing and substance use disorders.

Cells Use ‘Bioelectricity’ To Coordinate and Make Group Decisions

According to the new results, as epithelial tissue grows, cells are packed more tightly together, which increases the electrical current flowing through each cell’s membrane. A weak, old, or energy-starved cell will struggle to compensate, triggering a response that sends water rushing out of the cell, shriveling it up and marking it for death. In this way, electricity acts like a health checkup for the tissue and guides the pruning process.

“This is a very interesting discovery — finding that bioelectricity is the earliest event during this cell-extrusion process,” said the geneticist GuangJun Zhang of Purdue University, who studies bioelectrical signals in zebra fish development and wasn’t involved in the study. “It’s a good example of how a widening electronic-signaling perspective can be used in fundamental biology.”

The new discovery adds to the growing assortment of bioelectrical phenomena that scientists have discovered playing out beyond the nervous system, from bacteria swapping signals within a biofilm to cells following electric fields during embryonic development. Electricity increasingly appears to be one of biology’s go-to tools for coordinating and exchanging information between all kinds of cells.

Collision-induced ribosome degradation driven by ribosome competition and translational perturbations

How cells eliminate inefficient ribosomes.

Inside every cell, ribosomes act as tiny but vital factories that build proteins, translating genetic information into the molecules that sustain life. Although ribosomes share the same basic structure, not all of them work with equal precision. Until now, scientists did not fully understand how cells detect and handle ribosomes that underperform.

Addressing this question, a team of researchers has identified a quality control mechanism that ensures only the most competent ribosomes survive. Their study, published in Nature Communications shows that ribosomes compete during protein synthesis. When translation is disrupted, the less efficient ribosomes are selectively broken down, while the stronger ones continue functioning.

Using biochemical and genetic analyses in yeast, the researchers examined how ribosomes behave when translation is disrupted. The team engineered cells to contain a functional but suboptimal ribosome variant. These slower-moving ribosomes are overtaken on messenger RNA by faster, native ribosomes, causing the two types to collide. Such ribosome-ribosome collisions activate a ubiquitination-dependent quality control pathway that selectively removes the less efficient ribosomes.

The team also explored how external factors, such as the anticancer drug cisplatin affect this process. Cisplatin, known for binding to RNA and DNA, was found to increase ribosome collisions, which in turn promoted ribosome degradation. This insight could improve understanding of how the drug acts inside cells and why it sometimes causes side effects.

The implications of this discovery extend beyond basic biology. By showing how cells maintain the quality of their protein factories, the study provides a foundation for understanding disorders caused by ribosome malfunction, known as ribosomopathies. It may also open the door to new approaches for improving the safety and effectiveness of certain drugs.

Johns Hopkins Scientists Identify Key Brain Protein That May Slow Alzheimer’s

Researchers at Johns Hopkins Medicine report that findings from a new study funded by the National Institutes of Health are helping to identify a promising new biological target for Alzheimer’s disease. The focus is a protein that produces a crucial gas within the brain.

Studies in genetically engineered mice show that the protein Cystathionine γ-lyase, also known as CSE, plays an essential role in forming memories, says Bindu Paul, M.S., Ph.D., an associate professor of pharmacology, psychiatry and neuroscience at the Johns Hopkins University School of Medicine who led the research. CSE is best known for generating hydrogen sulfide, the gas responsible for the smell of rotten eggs, but the new findings highlight its importance in brain function.

Mapping gene disruptions in sporadic early onset Alzheimer’s disease across key brain regions

A new study led by researchers at UTHealth Houston investigated both gene expression and regulation at single cell levels to reveal disruptions in gene function in three brain regions of patients with sporadic early onset Alzheimer’s disease.

The findings are published in Science Advances.

Only about 5% to 10% of patients with Alzheimer’s disease are younger than 65. Of those patients, 10% have mutations in the APP, PSEN1, and PSEN2 genes, which are associated with Alzheimer’s disease. The other 90% of these cases are classified as sporadic early onset Alzheimer’s, a rare and aggressive form of the disease that begins before age 65. The genetic tie in early onset Alzheimer’s is largely unidentified, representing a significant but understudied population.

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