As humans age, our cells undergo a process called senescence, where they become dysfunctional and can no longer divide. This leads to a range of age-related diseases and physical decline. Scientists have been studying this phenomenon in the hopes of finding new ways to promote cellular renewal and prevent or reverse aging. Recently, researchers made a groundbreaking discovery that sheds light on the mechanisms behind cellular senescence.

Using Caenorhabditis elegans (C. elegans), also known as nematode worms, scientists manipulated a specific gene called TFEB, which regulates cellular responses to nutrient availability. When these worms were subjected to long-term fasting followed by refeeding, they typically regenerated and appeared rejuvenated under normal conditions. However, when the researchers removed TFEB from the equation, the worm’s stem cells failed to recover from the fasting period and instead entered a senescent-like state.

This senescent-like state was characterized by various markers, including DNA damage, nucleolus expansion, mitochondrial reactive oxygen species (ROS), and the expression of inflammatory markers – all similar to those observed in mammalian senescence. This finding provided scientists with a new model for studying senescence at the organismal level.

According to Adam Antebi, head of the study and director at the Max Planck Institute for Biology of Ageing, “We present a model for studying senescence at the level of the entire organism. It provides a tool to explore how senescence can be triggered and overcome.”

The researchers discovered that TFEB plays a crucial role in responding to fasting by regulating gene expression. Without it, worms attempt to initiate growth programs without sufficient nutrients, leading to senescence. They also identified growth factors like insulin and transforming growth factor beta (TGFbeta) as key signaling molecules dysregulated upon TFEB loss.

This new understanding of the TFEB-TGFbeta signaling axis has implications for finding treatments targeting senescent cells during aging as well as cancer dormancy. The researchers aim to test their worm model in the future to find new treatments targeting these areas.

In summary, this groundbreaking study sheds light on the mechanisms behind cellular senescence and provides a powerful tool for exploring how senescence can be triggered and overcome.

The study, published in Science, has provided conclusive evidence that neurons continue to form well into late adulthood in the brain’s memory centre, the hippocampus. Led by Jonas Frisén, Professor of Stem Cell Research at Karolinska Institutet, the research aimed to answer a fundamental question about human brain adaptability.

The hippocampus plays a crucial role in learning and memory, as well as emotion regulation. A previous study by Frisén’s group in 2013 demonstrated that new neurons can form in the adult human hippocampus. However, the extent and significance of this neurogenesis were still debated.

In the latest study, researchers combined advanced methods to examine brain tissue from individuals aged 0 to 78 years from international biobanks. They used single-nucleus RNA sequencing, flow cytometry, and machine learning to identify different stages of neuronal development, including stem cells and immature neurons in the division phase.

The results confirmed that neural progenitor cells exist and divide in adult humans, providing an important piece of the puzzle in understanding human brain changes during life. The study also found variations between individuals in terms of neural progenitor cell presence, with some adults having many such cells while others had hardly any.

These findings may have implications for regenerative treatments that stimulate neurogenesis in neurodegenerative and psychiatric disorders. The research was conducted in collaboration with Ionut Dumitru, Marta Paterlini, and other researchers at Karolinska Institutet, as well as Chalmers University of Technology in Sweden.

The study received funding from the Swedish Research Council, European Research Council (ERC), Swedish Cancer Society, Knut and Alice Wallenberg Foundation, Swedish Foundation for Strategic Research, StratRegen programme, EMBO Long-Term Fellowship, Marie Sklodowska-Curie Actions, and SciLifeLab. Jonas Frisén is a consultant for 10x Genomics, as disclosed in the scientific article.

Cancer cells have a notorious ability to multiply rapidly and spread easily throughout the body. One of the reasons they are so successful is their ability to undergo a process called epithelial-to-mesenchymal plasticity, which makes them resistant to elimination by anticancer therapies. In an effort to find new ways to combat this resistance, researchers have been searching for newer anticancer agents that can target these “rogue” cancer cells.

A team of scientists led by Dr. Hideyuki Saya, Director of the Oncology Innovation Center at Fujita Health University in Japan, has made a groundbreaking discovery about the potential of benzaldehyde to halt therapy-resistant pancreatic cancer. This sweet-smelling molecule is responsible for the aroma of almonds, apricots, and figs, but it also has potent anticancer properties.

The researchers were driven by a desire to uncover the mechanism behind benzaldehyde’s anticancer effects, particularly after learning that one of their colleagues had demonstrated its potential back in the 1980s. The first author of the study, Dr. Jun Saito, was motivated by her parents’ pioneering work on benzaldehyde and its derivatives.

The team conducted extensive research using a mouse model grafted with growing pancreatic cancer cells. They found that benzaldehyde inhibited the growth of these cancer cells, even when they had become resistant to radiation therapy and treatment with osimertinib, an agent blocking tyrosine kinases in growth factor signaling.

Their findings revealed that benzaldehyde exerts its anticancer effects by preventing interactions between a key signaling protein called 14-3-3ζ and histone H3. This interaction is crucial for cancer cell survival and treatment resistance. By blocking this interaction, benzaldehyde reduced the expression of genes related to epithelial-mesenchymal plasticity.

The study also showed that benzaldehyde synergized with radiation therapy to eliminate previously resistant cancer cells. Furthermore, a derivative of benzaldehyde was found to inhibit the growth of pancreatic tumors and suppress epithelial-to-mesenchymal plasticity, preventing metastasis.

Dr. Saya’s team believes that their results suggest that inhibition of the interaction between 14-3-3ζ and its client proteins by benzaldehyde has the potential to overcome the problem of therapy resistance. This study opens up possibilities for using benzaldehyde as a combinatorial anticancer agent, alongside molecular-targeted therapies.

The implications of this research are significant, offering new hope for patients with therapy-resistant pancreatic cancer. Further studies will be necessary to confirm these findings and explore their potential applications in the clinic.