#cd38

[huntforlongevity]

And again about NAD+

Why do we talk about NAD+ again? Because it is the most important molecule for life to exist, and our health directly depends on its amount in our body! Learn here how your body gets NAD+, how it uses it, why its level decreases with age, and how to measure, maintain, and potentially increase your NAD+ levels. Read the full article

[huntforlongevity]

And again about NAD+

Why do we talk about NAD+ again? Because it is the most important molecule for life to exist, and our health directly depends on its amount in our body!This post will help you to understand how your body gets NAD+, how it uses it, and why its level decrease with age based on the latest studies and discoveries. Also... It contains practical advice on how to measure, maintain and potentially increase your NAD+ levels, including references to useful products and services. The three recipes below are from the book "The Longevity Diet: Slow Aging, Fight Disease, Optimize Weight" by Dr. Valter Longo; that definitely worth adding to your diet.

How does our body get NAD+?

Just to remind, NAD+ stands for Nicotinamide Adenine Dinucleotide, a crucial coenzyme that can be found in every cell in your body. NAD+ works as a shuttle bus, transferring electrons from one molecule to another within cells to carry out all sorts of reactions and processes. With its molecular counterpart, NADH, this vital molecule participates in various metabolic reactions that generate our cell’s energy. Without sufficient NAD+ levels, our cells wouldn’t be able to generate any energy to survive and carry out their functions. Other functions of NAD+ include regulating our circadian rhythm, which controls our body’s sleep/wake cycle.  Basically, without NAD+, we would be on the fast track to death. In our previous post, we already showed what food sources provide us with NAD+ precursors for its synthesis inside the cells. There are five major precursors and intermediates to synthesize NAD+: tryptophan (Trp), nicotinamide (NAM), nicotinic acid also known as niacin (NA), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN).  NAD+ can be synthesized de novo by the conversion of the amino acid tryptophan (Trp) through multiple enzymatic steps to nicotinic acid mononucleotide (NAMN). This is one of three known pathways to produce NAD+ in a body, called the Kynurenine pathway. You can find more information on how NAD+ is made by this pathway here. NAD+ can also be made by the Preiss–Handler pathway starting from niacin (NA), a form of vitamin B3. It is known for producing flushing when taken in high amounts. Conversion to NAD+ proceeds in several enzymatic steps. NANM is an intermediate in the pathway, so de novo synthesis from tryptophan shares several steps in this pathway to complete NAD+ synthesis. But most of our NAD+ we get from the third pathway,  called the Salvage pathway. This pathway converts nicotinamide (NAM) to NAD+ with nicotinamide mononucleotide (NMN) as an intermediate. Learn more here.

How is NAD+ consumed in the body?

We already know that NAD+ is a vital coenzyme in redox reactions. It is responsible for accepting "high energy" electrons and carrying them ultimately to the electron transport chain, where they are used to synthesize ATP molecules. Why is it important? Because ATP, or adenosine triphosphate, is an important “energy molecule” found in all life forms. ATP captures chemical energy obtained from the breakdown of food molecules and releases it to fuel cellular processes, such as transcription, DNA replication, DNA repair, and many others. NAD+ has a cofactor in the process of ATP synthesis, which is flavin adenine dinucleotide (FAD+).  FAD+ is a coenzyme form of vitamin B2. When these electron-carrier molecules (NAD+ and FAD+) accept the electrons, they are reduced into NADH and FADH2 (redox reactions). These electrons usually come in the form of hydride atoms. Reduced forms are oxidized back to NAD+ and FAD+ during ATP synthesis. So, here, NAD+ is in the cycle. But... NAD+ is also constantly consumed in cells by the action of a number of NAD+ consumers, including sirtuins, PARP enzymes, SARM1, and CD38. Let's go over with each of these enzymes. Learn more here.

Why does NAD+ decline with age?

NAD+ levels decline in many tissues with age, and this decline is believed to contribute to the aging process. Multiple factors can play a role in the decline, including dietary deficiencies for NAD+ precursors, changes in the expression levels of enzymes that transform dietary precursors to NAD+, or changes in the activity of enzymes that break down NAD+ (see above).  Diet-induced metabolic damage is related to increased activity of PARPs and CD38 following increased DNA damage and inflammation, and NAD+ consumption.  A sedentary lifestyle could be enough to decrease mitochondrial amounts in muscles and, consequently, NAD+ levels, even in the absence of a disease state or changes in NAD+-consuming enzyme activities. There is also a suggestion that the synthesis of NAD+ declines with age and fails to compensate for its consumption. The constant degradation of NAD+ by enzymes involved in various cellular processes requires a continuous resupply of it by synthesis from dietary precursors or recycling from NAD+ degradation products. As shown above, NAD+ recycling via the NAM salvage pathway is a fundamental step to restore NAD+ levels after irreversible degradation mediated by the different classes of NAD+-consuming enzymes (Sirtuins, PARPs, CD38, and SARM1). Learn more here.

How to measure NAD+ level?

Learn more here.

Read the full article

[didanawisgi]

Abstract

A series of thiazoloquin(az)olinones were synthesized and found to have potent inhibitory activity against CD38. Several of these compounds were also shown to have good pharmacokinetic properties and demonstrated the ability to elevate NAD levels in plasma, liver, and muscle tissue. In particular, compound 78c was given to diet induced obese (DIO) C57Bl6 mice, elevating NAD > 5-fold in liver and >1.2-fold in muscle versus control animals at a 2 h time point. The compounds described herein possess the most potent CD38 inhibitory activity of any small molecules described in the literature to date. The inhibitors should allow for a more detailed assessment of how NAD elevation via CD38 inhibition affects physiology in NAD deficient states.

[biolegend]

Travel Award Winner Interview with Courtney Long

BioLegend provides a monthly $500 Travel Award for junior investigators in the US and Canada, as well as a separate £300 Travel Award for the UK. So far, BioLegend has provided over $28,000 in Travel Awards, supporting researchers' ability to travel to scientific meetings worldwide. We had a chance to catch up with and interview one of the winners of the Travel Award, Courtney Long, graduate student from The University of Oklahoma Health Sciences Center. Here's what she had to say about her experience winning the Travel Award and the conference she attended: What is your area/field of study? Osteoimmunology What conference did you attend? The 4th International Conference on Osteoimmunology: Interactions of the Immune and Skeletal Systems in Corfu, Greece. Did you present any materials/papers at this conference, and if so, can you give a brief description of the paper you presented? I presented a poster about the role of E proteins in osteoclast development. The E proteins are a family of transcription factors widely expressed in immune cells. When E protein activity is analyzed in a gain of function model, we detect an increase in bone mass. The reason for increased bone mass is because of fewer osteoclasts, or bone resorbing cells, due to apoptosis in homeostatic conditions. Through sequencing techniques, we discovered that the E proteins can upregulate expression of an ectoenzyme named CD38. This protein has previously been shown to have anti-osteoclastic capabilities. When we knocked down CD38, we were able to return cells with an E protein gain of function to normal survival rates. How was your overall experience of the conference you attended? It was wonderful. I got to meet with people from all over the world and form excellent networking connections. Not to mention, we had tons of wonderful Greek food in the most unique places. Did you do any "touristy" things when you were in the city where your conference was? If so, describe them briefly. Yes, the Aegean Conference coordinators took us on a tour of Corfu by bus. We got to see a palace, a fortress, and downtown Corfu. What was your overall experience with the BioLegend Travel award program? It was amazing. BioLegend made it possible for me to attend this conference. I was able to meet graduate students and potential mentors from other countries, visit an island I might otherwise not have been able to, and present my research to my colleagues to get very helpful feedback. Would you recommend this program to others, if so, why? I definitely would. It's a very easy program to work with and it opens doors that might have otherwise been closed. Do you need travel support to get to your next conference? Sign up for the BioLegend Travel Award today!