What changes happen in the aging brain?

Neurodegenerative diseases affect more than 57 million people globally. Though scientists know that aging is a major risk factor for neurodegenerative diseases, the mechanisms underlying its impact remain unclear. But a great place to start is epigenetic change—the way small chemical tags on top of our base genetic code shift over time to alter gene expression. Joseph Ecker, PhD, Margarita Behrens, PhD, and colleagues have created the most comprehensive single-cell atlas of epigenetic changes in the aging mouse brain to date. The new atlas represents eight brain regions and 36 distinct brain cell types, with more than 200,000 single cells profiled across methylation and chromatin conformation assays, plus nearly 900,000 cells captured with spatial transcriptomics. The contents have already revealed clear epigenetic differences across age groups and enabled the researchers to develop novel deep-learning models that predict age-related gene expression changes. Read news release

What keeps thirsty plants alive during drought?

For more than 25 years, the American Southwest has faced the severe social and economic consequences of a megadrought, including a $1.1 billion agricultural loss in California in 2021 alone. New research led by Joseph Ecker, PhD, provides a roadmap that could help researchers engineer crop varieties that get us out of this agricultural rut.  The team profiled nearly a million cells from the leaves of Arabidopsis thaliana, a small flowering plant that serves as a laboratory stand-in for important crops like corn, wheat, and rice. They measured changes in gene expression in these cells across different drought levels and leaf developmental stages and compiled the data in a public atlas. The atlas revealed that drought conditions accelerate leaf aging, but a specific gene could be used to rescue leaf growth during drought. Read news release

Mitochondrial DNA can impact human health and disease

Some of your most important life partners are the mitochondria that power all your cells. You and these little cellular powerhouses are in a 1.5-billion-year-old evolutionary relationship—but mitochondria brought some baggage. Mitochondria brought their own DNA with them when they joined with our bigger, more complex cells so long ago, and today, that mitochondrial DNA influences human health. Ronald Evans, PhD, is asking what those influences are, and the latest study from his lab unveils a new biological platform for studying mitochondrial DNA in physiology, adaptation, disease mechanisms, and therapeutic development. They have already used the platform to generate a library of 155 mitochondrial DNA mutant cell lines and to reveal correlations between mouse development and mitochondrial function. The platform, library, and findings will accelerate therapeutic development for mitochondrial disorders and help scientists treat mitochondrial dysfunction in other diseases and conditions, such as cancer and aging.  “The majority of human diseases come with or cause mitochondrial dysfunction. Progress in this field has been limited, but this new platform is going to fuel so much important research that points to therapeutic approaches to combat mitochondrial diseases, as well as diseases or conditions associated with mitochondrial dysfunction like cancer or aging.” Ronald…

Visualizing cellular life with greater precision

Fluorescent proteins have revolutionized science, enabling researchers to tag and visualize individual molecules in living cells, tissues, and animals. Using these tools, researchers have watched viruses infect cells in real time, observed cellular waste collection, and tracked the signaling that spurs tumor growth. Axel Nimmerjahn, PhD, worked with collaborators at Albert Einstein College of Medicine to advance this visualization technology.  Their new technology, called visible-spectrum antigen-stabilizable fluorescent nanobodies (VIS-Fbs), was validated across multiple mammalian cell types and provides a powerful tool for a wide range of life science research applications. Scientists can now gain more accurate, timely insight into cellular activity—even in complex environments such as living brain tissue. “This work establishes a versatile platform for imaging proteins with high specificity and minimal background. It opens new opportunities to study how molecular and cellular processes unfold in real time across diverse biological systems.” Axel Nimmerjahn Read news release

Can naked mole rats peacefully hand over power?

Naked mole rats keep kingdoms underground. One queen bears all the children, while other mole rats maintain complex subterranean tunnels, forage for food, take care of newborns, and perform other necessary upkeep. This society hinges on the central pillar of a singular queen. For years, the prevailing view has been that succession in naked mole rat colonies is violent and chaotic.  New research led by Janelle Ayres, PhD, suggests it does not have to be that way. Her team found that when reproduction is impaired in an established queen, peaceful succession is possible within an established naked mole rat colony. The study illuminates a new layer of social complexity for naked mole rats, which are important models in biomedical research on socialization, aging, adaptation, fertility, and more. The findings also help answer broader questions about biological resilience, potentially revealing principles that can explain human health and disease. Read news release

From Salk Institute discovery to patient care: Vitamin D analog shuts down pancreatic cancer’s shield in clinical trial

A small clinical trial led by the Dana-Farber Cancer Institute put a Salk Institute idea to the test in patients: that activating the vitamin D receptor can help reshape the protective environment surrounding pancreatic tumors in ways that could make the notoriously difficult-to-treat cancer more vulnerable to therapeutic treatments. In the study co-authored by Ronald Evans, PhD, patients with previously untreated metastatic pancreatic cancer received standard chemotherapy with or without paricalcitol—a vitamin D analog that is already FDA-approved for other uses. In patients who received paricalcitol orally or intravenously, the combination was found to be safe and to reduce activation of fibroblasts in the tumor microenvironment, validating Salk’s preclinical findings. The trial was not intended to measure how well the approach works in treating pancreatic cancer, yet the researchers noted improved chemotherapy responses and increased progression-free survival at one year among patients who received paricalcitol plus chemotherapy. In addition, they found that patients with high vitamin D receptor expression and who received paricalcitol had the longest overall survival rate. “This study really takes a novel approach for cracking therapeutic resistance in pancreatic cancer. By using vitamin D analogs to engage the body’s own natural system for dampening fibrotic and inflammatory…