Alternative for longer life! Syed Shamsh Tabrez on how alternative splicing increases lifespan during dietary restriction.

Celebrating 100th birthday in good health! Who doesn't want that. With modern medicine, more and more people are living longer and healthier lives. And diet plays a major role in helping us live longer. Scientific evidence points more and more towards a low-calorie diet leading to increase in lifespan. But eating less to restrict calories is so tough! Everyone wants to have an ice-cream at the end of the day. Is it possible to eat indulgent food and still extend lifespan?

Tabrez and colleagues wanted to understand the basic biological changes that occur with dietary restriction. Illuminating the underlying principles would help harnessing them for increasing lifespan. They found that during dietary restriction, the genetic information processing is altered and this changes the biological landscape of the cells. Such alterations could help cells with efficient energy processing. To know more, please listen to Tabrez.




To know more, please refer to:
Differential alternative splicing coupled to nonsense-mediated decay of mRNA ensures dietary restriction-induced longevity
Tabrez et al., Nature communications, 2017

The sugar deception! Interview with Maria Veldhuizen to know if our brain can tricked into uncoupling sweetness from calorie content.

We all know of diet drinks and sugar-free desserts. Such foods have ingredients that are sweet, but low in calorie. The temptation to savor and relish sweet foods without paying the price of high calorie intake is pretty tempting, isn't it? But does taking food items with a mismatch in sweetness and calorie content actually work on our brains? Can our brain detect the disparity?

Maria and colleagues wanted to understand the affect of discrepancy between the sweetness of the food and its calorie content on the brain's response and metabolism. By providing people drinks that were of the same nutritional value, but varying in calorie, they found that the body responded the best when the two things, sweetness and calories, matched. This suggested that calories are not the only factor that trigger metabolic and mental responses. It could be that the brain's reward circuits better register foods that match in their sweetness and nutritional content. This is of great importance because we live in a world where increasing amounts of food contain such mismatches. To know more, please listen to Maria.


To know more, please refer to:
Integration of Sweet Taste and Metabolism Determines Carbohydrate Reward
Maria et al., Current Biology, 2017

A Mito coup d'cellule! Interview with Hansong Ma on selfish drive in mitochondria!!!

Mitochondria are the power generators of the cell. Each cell has thousands of them, and each has its own genome. The DNA it possesses is needed for survival, and it has to be replicated to generate new ones. This means that mitochondria that can replicate better can out-compete others with replicative disadvantage and, in extreme cases, take over the entire cellular compartment. Since, the cell is blind to such competition, 'bad' or non-functional mitochondria can take over, to their own benefit and to the cell's detriment; thereby leading to 'selfish behavior'. 

This is of particular importance to current human health. UK's decision to allow three-parent baby is a monumental step in curing a set of congenital diseases. In this the defective mitochondria is replaced with that from a healthy donor. But even if a few defective ones remain behind (from among thousands), this also creates a competition among the two populations. And if the selfish drive of the defective one is strong enough, it might again take over the cell, thereby increasing the chance of pathogenesis. A good donor should not only be healthy, but also strong in its selfish drive. To understand how such competition is accomplished, please listen to the interview with Hansong Ma.

For more information, please refer to:

Selfish drive can trump function when animal mitochondrial genomes compete.

Ma and O'Farrell. Nature Genetics 48, 798–802 (2016).

Eat me not! Interview with Anu Chaudhary on cell surface marker regulating autophagy in humans!

Cells are constantly talking with each other, mostly with the help of cell surface receptors and ligands. This includes information on the amount of 'self-digestion' to perform. Higher self-digestion, or autophagy, leads to faster protein turnover and has been implicated in many age-related diseases, esp. those with an autoimmune component. Could we understand the mechanism controlling levels of autophagy and modulate it to affect disease outcomes?

Anu Chaudhary and her colleagues display an elegant way to screen human genetic variation underlying any observable phenomena. By focusing on response to rapamycin, a drug that induces autophagy, they were able to isolate variations that enhance cellular self-digestion. They use this to characterize cell surface receptors that can vary autophagy levels, and use this knowledge to develop means that could deter auto-antibody production. To learn more about the exciting and relevant finding, please listen to Anu.


For further information, please refer:
Human Diversity in a Cell Surface Receptor that Inhibits Autophagy.
Chaudhary et al., Current Biology, 2016.

Exercising the old away! -- Interview with Marissa Schafer about exercise decreasing senescent adipocytes!!

We all know the many benefits of exercise, and the evils of fast-food diet. Exercise makes us feel healthy, younger and more vital; while excess of double cheeseburgers gives the lethargic look with tired body. But how exactly does exercise lead to such benefits; and high fat diet lead to such deterioration?

Marissa Schafer and her colleagues at Mayo Clinic asked this simple, yet complex question. What they saw was that high-fat diet was increasing the proportion of senescent fat cells -- cells that are incapable of growing or diving. They saw that such cells were attracting immune system components, that could lead to adverse effects. Exercise on the other hand decreased the presence of such cells, excitingly even in the case of high-fat diet. So, if you have a hamburger, be sure to couple it with a 5k. To know more the exciting study, please listen to the interview with Marissa:


Please refer the following for more information:
Exercise Prevents Diet-induced Cellular Senescence in Adipose Tissue.
Schafer et al., Diabetes 2016.  

Not starving to death: Interview with Manqi Wang about glycemic control during fasting!

Have you ever missed a meal, maybe two. But your brain still keeps working, doesn't it. It still keeps getting the glucose it needs to think. Without this sustained blood glucose regulation during fasting, our body can go into a hypoglycemic shock that can be fatal. What regulates such important network.

Manqi Wang and her colleagues investigated the role of autonomous nervous system during prolonged starvation. They interestingly found that the reflex pathways plays an important role. Surprisingly, they see that the system is highly plastic and changes network strengths based on physiological demands. To learn more, please listen to Manqi!



For more information, please refer to:
Fasting induces a form of autonomic synaptic plasticity that prevents hypoglycemia.
Wang et al., PNAS 113.21 (2016): E3029-E3038.

How is more important than What! -- Interview with Jonathan Coloff about Glutamate usage during function vs. proliferation!!

Cells perform their function: like heart muscle makes the heart beat or beta-cells maintain blood glucose by secreting insulin. This demands energy and resources to accomplish that. Many times, the same cells need to increase their numbers to meet the body's every changing demands. Like beta-cells multiple in cases of obesity. Cell division is also an energetically costly process. It has to make two of almost everything: two sets of DNA, two times the mitochrondria, before dividing into two. How does the cell balance the resources between its function and cell division processes?? 

Jonathan Coloff and colleagues asked the same and found that the answer does not lie in different starting material, but how the raw materials are processed. A cell's carbon demands can be satisfied by glucose, but nitrogen comes mostly from glutamate; which helps build nuclei acids, proteins and other machinery. Quiescent cells performing normal function process glutamate to ammonia vs. proliferative cells that would make non-essential amino acids from it. This difference in processing describes the switch between the two cellular states. To learn more about the switch, please listen to Jon.

To know more about the study, please refer to:

Differential Glutamate Metabolism in Proliferating and Quiescent Mammary Epithelial Cells
Jonathan L. Coloff et al., Cell Metabolism. May 2016.

Shaping the microbiota: Long-lasting effects of antibiotics and talking via miRNA - Interview with Katri Korpela and Shirong Liu!

A human body is not only made up of eukaryotic cells, but lives in symbiosis with almost an equal number of bacterial cells. This rich collection of bacteria co-existing with our body is called microbiota. Specifically, the gut microbiota - bacteria living in our intestines -find insights into the relationship are of special importance since they can shape metabolism, mood and susceptibility to diseases. How is this colony of bacteria regulated forms the basis of this two-part podcast.

In the first part, we talk about the effects antibiotics could have on microbiota. The Microbiota is set up at birth. In kids, the microbiota is highly dynamic, and settles into stable colony by adulthood. What happens when the process of microbiota formation is afflicted by antibiotic usage. Does it ever recover back to normalcy following antibiotic exposure. Katri Korpela and colleagues set out to study the long term relation between antibiotics and microbiota in Finnish pre-school children. Listen in to find insights into the relationship.

In second part, we talk to Shirong Liu who along with his colleagues found the communication device used by our body to stabilize microbiota colony. Microbiota stays stable over long periods of time in adult individuals, and they looked at the role played by miRNA in the process. miRNA are small RNA molecules that regulate gene expression. Liu and colleagues found that our body uses miRNA to shape the microbiota diversity and such miRNA can be detected in fecal samples. This interesting finding opens the door to non-invasive diagnostic devices to look at health and composition of microbiota. Please listen in to find more!!


To know more, please refer to the following articles:

First part (Antibiotics and microbiota):
Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children
Katri Korpela et al., Nature Communications 7, Jan 2016

Second part (Regulation by Fecal miRNA):
The Host Shapes the Gut Microbiota via Fecal MicroRNA
Shirong Liu et al., Cell Host and Microbes, Volume 19, Issue 1, p32–43, 13 January 2016

Introduction and closing by Priyanka Oberoi.

A fat hope for autism! - Interview with Zhigang Xie on role of fatty acid metabolism in neuronal stem cells.

Autism is a distressful condition with impaired social interaction and communication. At its basis, it is a neurodevelopment disorder, with certain areas of the brain not developing properly. The burden of brain development falls on neural stem cells, which divide to generate functional neurons as well as maintaining their own numbers. Zhigang Xi and his colleagues show that fatty acid beta-oxidation seems to play a major role in maintaining the stem cells involved in autistic behavior. How is this achieved -- to know the answer, we call Zhigang Xi.


Please read the original article here:
Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to Autism
Xie et al., Cell Reports (2016). Volume 14, Issue 5, p991–999.

How we sense hunger? Interview with Zhiying Li.

What tells our body that it needs food?? The answer might lie within the working of a hormone called leptin. The hormone, mostly secreted by fat tissue, works on a small area of the brain, the hypothalamus, to control hunger and satiety. Its decrease leads to over-eating and obesity. Now, Zhiying, a post-doc in Jeffery Friedman's Lab at Rockefeller University, finds that the molecule might have a brother-in-arms for control of such feelings. In her article published in Cell Metabolism, she finds that another peptide hormone, amylin, works in concert with leptin and enhances its effect. Combinational therapy with both amylin and leptin seem to have better effect on controlling obesity. We ring her up and try to find more about this new synergy!


Read the article for yourself:
Hypothalamic Amylin Acts in Concert with Leptin to Regulate Food Intake
Li et al., Cell Metabolism, Dec. 01, 2015.