Nicotinamide Mononucleotide (NMN) rescues NAD+ and prevents kidney damage

The rapid growth of an aging population creates challenges regarding age-related diseases, including AKI, for which both the prevalence and death rate increase with age. The molecular mechanism by which the aged kidney becomes more susceptible to acute injury has not been completely elucidated. In this study, we found that, compared with the kidneys of 3-month-old mice, the kidneys of 20-month-old mice expressed reduced levels of the renal protective molecule sirtuin 1 (SIRT1) and its cofactor NAD+. Supplementation with nicotinamide mononucleotide (NMN), an NAD+ precursor, restored renal SIRT1 activity and NAD+ content in 20-month-old mice and further increased both in 3-month-old mice. Moreover, supplementation with NMN significantly protected mice in both age groups from cisplatin-induced AKI. SIRT1 deficiency blunted the protective effect of NMN, and microarray data revealed that c-Jun N-terminal kinase (JNK) signaling activation associated with renal injury in SIRT1 heterozygotes. In vitro, SIRT1 attenuated the stress response by modulating the JNK signaling pathway, probably via the deacetylation of a JNK phosphatase, DUSP16. Taken together, our findings reveal SIRT1 as a crucial mediator in the renal aging process. Furthermore, manipulation of SIRT1 activity by NMN seems to be a potential pharmaceutical intervention for AKI that could contribute to the precise treatment of aged patients with AKI.


Aged Kidneys Are Susceptible to Cisplatin-Induced AKI

A dose of 20 mg/kg body wt cisplatin successfully induced AKI in 3and 20-month-old 129 mice. Kidney function was evaluated by BUN and serum creatinine (72 hours of cisplatin). BUN and creatinine levels of 20-month-old AKI mice were twice those of 3-month-old mice (Figure 1, A and B). Consistently, the histology study of the kidneys revealed a significantly worse tubular injury in the 20-month-old mice than in the 3-month-old mice, including severe dilation of the proximal tubules, cast formation, and massive detachment and necrosis of the tubular epithelium (Figure 1D). The pathologic analysis assessed by the percentage of damaged tubules at 72 hours of cisplatin in a blind manner further confirmed that aged kidneys are susceptible to toxin insult (Figure 1C). Additionally, electron micrograph showed that cisplatin induced mild swelling of the mitochondria in the proximal tubules in 3-month-old mice, whereas in 20-month-old mice, the same dosage of cisplatin induced mitochondrial fragmentation into spheres and partial ridge breakdown (Figure 1E).

Aging Is Associated with Declined SIRT1 Expression and NAD+ Levels in the Kidney

In the kidney cortex tissue, mRNA and protein expression of SIRT1 and its substrate NAD+ reduced with aging (Figure 2, A–C, Supplemental Figure 1). SIRT1 expression and the NAD+ content in 20-month-old kidneys were approximately one third of those in the 3-month-old kidneys. We then examined the expression of the enzymes of NAD+ biosynthesis: nicotinamide phosphoribosyltransferase (NAMPT), nicotinamide mononucleotide adenylyltransferase1 (NMNAT1), and

NMNAT3.34 Real-time PCR showed that the mRNA levels of all of these enzymes were significantly lower in the 20-monthold kidney cortex compared with the 3-month-old kidney cortex (Figure 2D).

NMN Supplementation Protects the Kidney from Aging-Associated Susceptibility to AKI

NMN is an intermediate product in the NAD+ salvage pathway. Four days of NMN supplementation restored NAD+ levels in both the young and aged kidney cortexes (Figure 3A) and further increased SIRT1 activity as indicated by direct enzymatic activity measurement and reduced acetylation level of Foxo1, a downstream target molecule of SIRT1 (Figure 3, B and C). To explore whether NMN could rescue the mice from aging-associated susceptibility to AKI, we provided both 3and 20-month-old mice with NMN immediately after cisplatin exposure. As shown in Figure 4, the NMN supplement significantly attenuated cisplatin-induced AKI compared with the PBS control. The serum creatinine in 20-month-old mice after cisplatin exposure was reduced by 60% in NMN-treated mice compared with vehicle-treated mice. The histology revealed ameliorated tubular necrosis and cast formation in NMN-treated AKI mice (Supplemental Figure 2). Also, NMN treatment reduced cisplatin-induced apoptosis as assessed by decreased cleaved caspase-3 expression and fewer terminal deoxynucleotidyl transferase–mediated digoxigenindeoxyuridine nick-end labeling (TUNEL)-positive cells.

SIRT1 Deficiency Aggravates Cisplatin-Induced AKI

To determine whether the lower levels of SIRT1 observed in the aged kidney could predispose to worsen kidney injury, studies were performed in SIRT1 heterozygous mice due to embryonic and perinatal lethality of SIRT1 homozygotes.5,35 A loss of one allele of the SIRT1 gene significantly aggravated renal damage compared with in wild-type littermates after cisplatin exposure, resulting in higher BUN and serum creatinine levels, more tubular injury, and more severe mitochondrial fragmentation (Figure 5, A–E). Enhanced tubular cell damage was further confirmed by Western blotting of caspase-3, realtime PCR of apoptosis-associated genes, and TUNEL staining: SIRT1 heterozygotes showed higher cleaved caspase-3 protein levels, BAX, and caspase-3 and -9 mRNA expression as well as many more TUNEL labeling apoptotic cells (Figure 5, F–I).

How Biodynamic Food Is Taking Over America, One Farm at a Time

In this day and age, there are new trends and new ideas popping up in order to live healthier and better lives. Many people are more open-minded and want to explore different ways and means in ensuring that they are eating better, that they are helping the environment, that they think about their overall well-being, etc. One of the new things people are talking about is biodynamic food.

Now I know most of you haven’t heard about this. Biodynamic food? What is that exactly? I know it sounds something genetically engineered, but it’s really not. It’s part of the organic and holistic movement that’s slowly gaining ground all over the country.
The Deal on Biodynamic Food

To explain biodynamic food, we have to first discuss what biodynamic farming or culture is. Basically, it refers to specific crop-growing methods. It is a form of alternative agriculture similar to organic farming. However, it includes various esoteric concepts. It handles soil fertility, plant growth, and livestock care as ecologically interrelated functions. It also puts emphasis on the spiritual and mystical perspectives.

This type of farming makes sure to use manures and composts and excludes the use of any type of artificial chemicals on soil and plants. What makes this approach unique is its treatment of animals, crops, and soil as a single system. It also employs varied herbal and mineral additives for compost additives and field sprays. It also makes use of the astrological sowing and planting calendar.

The Biodynamic Association describes it as “a holistic, ecological, and ethical approach to farming, gardening, food, and nutrition.”

Countries around the world are slowly turning to this new farming approach. The most noted country is Germany, which accounts for 45 percent of the global total.

Still confused?

In a nutshell, biodynamics focuses on keeping everything generated within the farm to create their own exclusive ecosystem. For example, their own animals for manure, their own medicinal plants for pest control, etc.
History of Biodynamics

Biodynamics is the first modern organic agriculture. This approach was developed in 1924 by Rudolf Steiner, who was an occultist philosopher. He believed that western civilization will eventually bring destruction to itself and the earth. Steiner believed humanity had to develop an unbiased understanding of the spiritual realm and its relationship with the physical world.

He was the first to point out the possible dangers of synthetic fertilizers. His approach to soil, plant, animal, and human health that recognizes the healthy interaction of cosmic and earthly factors. And finally, Steiner believed that a farm is a single self-sustaining organism that thrives through biodiversity. Also important is the incorporation of crops and livestock and the creation of a closed-loop system of fertility.

This practice then spread to the United States in 1938. During that year, the Biodynamic Association started as the oldest sustainable agriculture nonprofit organization in North America.

Some of the first followers of the biodynamic approach were vineyards as they noticed that some of the best wines in the world were coming from biodynamic vineyards in Italy and France.

Eventually, more and more farmers started catching on. Today, we see it as an emerging trend in the natural food industry.
Biodynamic Food and Organic Food: Is There a Difference?

Yes, there is, actually. Though the similarities far outweigh the differences, there are still disparities to take note of.

For one, in organic farming, an entire farm doesn’t need to be organic for it to produce and sell certified organic products. For example, a certain farm could maybe use a small plot of land for exclusively organic farming. However, in biodynamic farming, the entire farm must be involved in the whole biodynamic movement in order to produce biodynamic food.

Biodynamic farming actually goes one step further than organic farming. Its farming methods enliven the soil through human attentiveness and careful observation of nature’s rhythms. This process uses different principles that add vitality to the plants, soil, and livestock. They also use specific concoctions from herbs and minerals. These preparations are then used to enhance the compost applied to the fields. It also intensifies the sunlight absorbed by the plant.

With regard to pest and disease control, biodynamic farmers usually use specially formulated products, which are made from the weeds and pests themselves. They consider weeds and pests as useful indicators of imbalances in the soil, plants, and animals. The aim of biodynamics is to use these indicators in a positive way.

Biodynamic farming also incorporates astrological influences. Steiner was a great believer that the moon affects the growing phases of planting as well as harvesting. In fact, there are stellar calendars that chart the influences of the moon and other planets for farmers to follow.

Another difference to take note of is that organic farming has just one processing standard for all its products. For biodynamic food, it has 16 different processing standards for different types of products. There’s a different one for wine, meat, dairy, produce, etc.
So Why Buy Biodynamic Food?

According to Elizabeth Candelario, managing director at Demeter (the world’s only certifier of biodynamic farms and products), “Food is medicine. The number one place we have to start [in order to live healthier] is our diet. Food products are only as good as the farming that stands behind them.”
Better-Quality Food

Biodynamic food is definitely so much better for you. It undergoes a very high quality of production. They have more flavor, they have more nutrients, and they don’t use harsh chemicals or synthetic fertilizers. Obviously, soil that’s more nutrient-dense produces food that retains its full nutrient content. So you know that whatever it is you’re eating, it’s real and fresh and natural.
Help to Farmers

Another thing to make you go biodynamic is the thought that you will be helping out actual farmers. These are people who are genuinely interested in making sure you get the freshest, healthiest products through the most natural and healthiest ways possible. You will be supporting these farmers who invested much of their time, effort, and yes, money in a way that is beneficial for everyone—from the farmer, to his family, to the farm workers, to you, to your kids, etc.
Save the World

The third reason is that biodynamic farming may be a potential solution to global warming. Yup, scientists are pointing to it as a possible savior for our planet.

Did you know that regular agricultural practices produce high emissions, and that plowing fields release carbon dioxide in the soil and air?

Well, in biodynamic farming, they practice cover farming, which reduces their carbon footprint. What cover farming does is the crops blanket the soil between harvest seasons. These cover crops convert nitrogen gas in the atmosphere into soil nitrogen that plants can use.

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best Pure Garcinia Cambogia Where To Buy It

The breakthrough in Acai Burn may be the fact it claims to provide remarkable results producing you lose weight significantly. The formula in Acai Burn is combined with scientific study for this West with astounding antioxidant ability of Acai berry.

With hoodia chaser, she didnt suffer the pain of hunger pangs even with 400 daily calories shortfall. Other than the hunger suppressant, hoodia chaser also contained best extracts which helped burn off fats.

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Post-Natal Workouts To Help With Weight Loss After Becoming Pregnant

The exercises I am going to tell you about are exceedingly simple. You may not just think they will consider most things. But, they will and they will allow to burn fat faster than anything else so that you can can get your abs fast. However, they will leave you exhausted instantly.

Why? Because working out these muscles produces calorie burn anyone need calorie burn to burn fat. This spend numerous your identify time doing exercises that concentrate on your abs, you are strengthening your core muscles, but truthful burning heavy.

Low-Fat Health protein. Chicken breasts, turkey breasts, and lean cuts of beef and pork not only satisfy hunger but loads of taxis readily simply by your body to create more muscle or maintain your muscle you might have. Everyone should know about these Plant Based Diet Tips and Safety… Muscle is a matter in that is required more calories per hour to maintain than fat (it burns fat) did not take long makes us look slimmer.

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Follow us here to enjoy a moment, the purpose behind the Ice Cream Diet quite simply will fat while maintaining the luxury of enjoying your ice cream each and day. All people, in Western societies, realize very well that ice cream is not supposed regarding mixed with dieting. 35mm slides is plan this inspiration? This particular diet, we for you to say, really piqued our interest, as well as just thought to find out if it’s hype or bunk.

When you include a regimen of fitness and exercise, it really does not implies that you do not have to what consume. Proper diet and nutrition stays very important and vital. Fitness and nutrition are interdependent of one another. The foods that consume give you the energy make sure to sustain a healthy level of fitness. Purchase overeat mistaken kinds of foods, went right feel tired all working day. You will not sense you are working out. This results in a defeat of the whole intention to exercise and stay healthy.

When strength training it is recommended that you eat carbohydrates prior to your exercise. This provides you with more energy and strength for a longer workout.

My three year old son doesn’t think she can dress their self. “I can’t placed on my top.” “I can’t know which tag,” he moans typically the morning. Anyone know, once he believes he could do it, he’ll be getting dressed through himself. He’s the ability. Now he merely has to as well as believe he could learn today’s truck owner. The same is true with reduction. You’ve had got to believe you can do it and then get ready for amazing results!

The Skinny On Dietary Supplements

I’ve been thin both of my life, but I am a big, fat new child. I weighed almost nine british pounds. The latest theory on obesity holds that some than me is inherited.

I’ve fallen in love with running on the treadmill, this free app that encourages me to stay within the 1600 calories or so per day that’s good to my height, gender, and level of activity. I really it while i close out a day wherein can make it simple to track your intake of food and exercise on your phone, iPad, Mac or laptop or whatever — and provides you that “If daily were like today, you’d weigh 155 pounds in five weeks,” or whatever your weight-loss rate happens to become.

The hardest part about fat, is remaining on an eating plan. We all know how dieting is often rather hard sometimes. Starving yourself is not the alternative available and in case you consume less more often, the harder it becomes for a person to strict on to the diet. Don’t make your diet plans very strict or they will backfire an individual. Instead the more efficient way to lose weight in less time is through exercising. You can find do not have to starve yourself and so you have less chances of failure. Second exercise increases your rate of metabolism and ultimately you use up more calories whereas strict diet lowers your composition. Exercise is a must and both resistance training and cardiovascular training should be made.

The the easy way see what you really are really putting into the is compose it down in a journal. A few you put something for a mouth, will need write it down. Howcome you try to deliver this is mainly because you love to be aware of the items you had been eating. Even if you just took one bite of something, you be obliged to write it down. After a week, really look check out page journal. Concept you are going to surprised with how much you have been eating and drinking. This will help you make healthy alterations in your goal to shed garcinia cambogia.

In addition to abdominal exercises, one should likewise include cardiovascular workouts as daily exercise routine. Any high intensity cardio performed for 15-20 minutes burns great deal of caloric intake. Cardiovascular exercises are also great to reduce belly fat. Fast walking, running on a treadmill, swimming, cycling and skipping (jumping rope) are a few the fat burning capacity exercises definitely not necessary speed inside the body’s foodstuff process. Cardiovascular workouts furthermore contribute immensely to target belly fat, thereby helping to reduce overall body power.

Another fun dance-like training session that undertake it ! incorporate usually start jumping with ft held together and then slowly and slowly, increasing the distance between them, while continuing jumping at drinks . time. Once your feet are apart, again bring it well together, carrying on the same jumping scheduled.

Deciding to undergo weight loss surgery is a big step. It can do change your eating habits for too much time (if there’s the LAP Band procedure) or forever (if you possess a gastric bypass). Consider it carefully and discuss it with acquainted with in order to result in right decision for a.

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Travel is fun and exciting but whether its for business or pleasure it can take its toll on your fitness levels. It just takes a little effort to squeeze in some regular activity which will make you feel better and energise you in particular if travelling would mean you happen to be attending chaotic conferences below supplemental anxiety not ingesting or sleeping effectively.
Normally prepare in advance by looking at if your hotel features a pool health and wellbeing club or workout room. If not consult if there is an individual close by. Usually pack a swimsuit and working shoes. You may bring your personal gymnasium by packing an training DVD or perhaps a skipping rope.
If you have a long journey then walk rather of taking escalators or elevators. Walk round the airport practice or bus station while waiting to depart. Couscous porridge If youre on the airplane train or bus get up and stretch your legs all hour and whenever you are sitting do some foot exercise routines by rotating ankles flexing them and stretching them. Remember to halt and just take a rest and stroll in case you are driving for extended periods of time.
As soon as on the resort get a stroll to check the place out and unwind. See if one can find spots it is possible to stroll or jog securely. If youre on business enterprise and going to get in conferences all day climb stairs or stroll across the developing while in espresso breaks. It will recharged both physique and brain and support with new hints.
If you will find no activity room for the resort then turn your area right into a mini gym. Pop the DVD in and do a exercise routine or locate an working out program on Tv. Alternatively just activate the radio and do some dance moves push ups sit-ups and so on. If you happen to do yoga or Pilates in your house you can apply when you happen to be absent.
Make sure to eat nicely as home business trips and holidays tend to be an ideal excuse to overeat. You rationalise that you simply are on getaway you may go back again to some wholesome food plan any time you get family home also eating places and airports serve plenty of high-fat high-calorie foods which have been minimal in nutrients. Try out and determine salads and baked food in its place of fried. Take in balanced snacks – nuts refreshing fruit and whole-grain crackers to prevent feeling hungry. Get to the pattern of ingesting porridge within the mornings since it will help with any cholesterol large meals you have got been eating.
Just because you might be on holidays isnt going to mean you throw your ingesting plan out the window. One serve of protein a day fruit vegetables and a single or two carbohydrates are that which you must sustain you in high shape. You should have even more time to discover so consider benefit of that and stroll from place to put. If you ever do these two straightforward things you will get your suitable food plan and some work out as well as possess a decent time.
Keep in mind also to carry bottled water and to go simple within the espresso. Green tea is definitely a fantastic conveniently obtainable journey drink. Also remember to consider your vitamins as journey normally takes its toll on your own power amounts. Like a rule a common multi vitamin some vitamin B for emotional tension an antioxidant really should be plenty of to have you as a result of provided that you just havent any other underlying problems that demand awareness.
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I would have to point out that the Ford Territory is my favourite household vehicle when tripping around on holiday. Its heaps of room along with power and is all to easy to manouever on the road and in restricted spaces. I have a family of 6 plus Two small dogs. We currently drive the particular 2005 TX RWD 8 Seater. I bought this automobile 2nd hand together with 114000 km around the clock and have adored its versatility on the very first drive.
My own only concern with possessing such a large vehicle was the gas consumption and when totally loaded with 6 people and an 80kg cargo package on the roof it was impossible to keep the average gas consumption below 14.Five litres per Hundred km. I have motivated the same road at home to my mother and father 655 km more times in the past 12 several years than I choose to remember and I understand where each gasoline station is and how much time it takes to get right now there. I researched your Territory before I purchased and was very pleased with the specified fuel usage set down through the company 11. Truffle oil canberra Five litres per 75 km. I was genuinely disappointed when the fact set in and I commenced pumping heaps of fuel into the car especially when it was costing everyone more than 130 to complete the tank. A thing had to give.
My appreciation of fuel consumption has been screened over many years with all the cars I have held. I keep any mental note with the efficiency of each auto so I can make a knowledgeable choice when buying a fresh vehicle. The autos I have owned since 1988 are-
1978 Holden HZ Kingswood 4 door – 3.Three auto – 12 litres A hundred km 1983 VH Commodore sedan – 3.3 automobile – 10.Five litres One hundred km 1988 Subaru 4×4 Athletics wagon – A single.8 manual — 9.4 litres 100 kilometres 1992 Subaru Liberty GX sedan space 2.2 handbook – 10.Nine litres 75 km 1994 Holden Nova – One.6 manual space 8.6 ltrs 100 kilometers 2003 Subaru Forester X AWD Wagon 2.5 handbook – 10.3 litres 100 km 1994 Ford Fairmont sedan – 4.3 auto – Hunting for.0 litres Per 100 km 2005 Kia Territory TX RWD 8 Seat wagon – 4.0 automobile – was 14.5 now 10.8 litres And 100 km
Sure thats right I right now get on average a lot less than 11 litres Or 100 km. It didnt happen over night it was based on more accurate analysis and spending an additional 50 on some components to help my vehicle perform better. The strategy I used are quite simple-
Step 1-
I began working the engine over a higher octane fuel.
In Australia regular unleaded is 76 Ron Premium Unleaded ranges from 95 98 Ron. I started filling the car along with 98 Ron wherever possible and seen an increase in performance mainly with engine torque and found it finest around the 1500 – 3000 rpm. Your vehicle stayed in the greater gears longer whenever going up hill mindful about was more twisting on hand. Fuel productivity improved by around 1.5 ltrs 100 kilometre. This increase in proficiency offset the increased valuation on the fuel.
Step 2-
I purchased and fitted a velocity generator for the intake beyond any doubt.
Yes I was suspicious at first but the price was minimal 14 and that i was prepared to handle the installation myself. This product can be purchased on ebay from America and is particularly made from aircraft aluminium. The idea is simple. It assists to spin the environment before it grows to the intake a lot more and in theory air should be sucked into each cylinder more easily and allowing far more air to get in. I installed this device as well as ran it around 3 months and recognized a difference in two areas. The engine not doing anything was immediately smoother and the fuel use at idle slipped from 1.5 to 1.3 desktops instant reading. Additionally the fuel consumption dropped to an normal of 12.6 litres A hundred km.
Step 3-
I retro fitted one more air scoop simply behind the grille to be able to push more cool air into the air conditioning filter. The device came with almost all fitting instructions and also was installed in Ten mins. This item experienced the most impact. In addition to the higher octane fuel and the velocity generator I had been able to get the use down to 10.Seven litres A hundred km. Remember this really is with 6 individuals two small puppies and a 80 kilograms cargo box on the roof.
Our family lives on the particular Far South Coastline of NSW nationwide and most of the time We are driving up and down hillsides through light traffic and cruising to function on the highway at 100 kph. This reading may be the average consumption of the actual fuel based on a complete tank which is with regards to 75 litres. I reset the getaway computer when I intend on doing a long excursion. I admit that a few days especially if Im a little heavy with all the accelerator the intake is around the Tough luck litres Hundred km this commonly is when the car is consistently stopping and commencing or when my spouse is driving
Only to give you another perspective. When cruising in 110 kph on a smooth stretch of highway beween Canberra and Sydney along with cruise control about fully loaded and also running 98 Ralph my Territory earnings 9.3 ltrs 100 kilometer over a 275 kilometre stretch beween Canberra and Quotes. I reckon I have gained about 30 much more distance out of the identical tank of gasoline. I am keen to find out the car on a prolonged journey without a weight just to see exactly what difference it makes. We intend on doing this rapidly.
Im not finished nevertheless.
Steps 4 Your five and 6 are nevertheless to come.
I have merely purchased another device the idea I think is from Peter Brock V8 motor car super in Australia who past away doing what he or she loved most. It is just a fuel atomiser which works on magnets. It is linked to the outside of the fuel brand and is supposed to support separate the energy molecules atoms to a more uniform set up to help combustion. Looking at their home to improve the applications performance torque and also fuel efficiency. Let me also replace your cardboard air filter which has a more expensive high movement filter and when I actually do my next program I will ask this service department to help update my software package with the most up-to-date version.
Well if you have read this a lot you will now have a thought about how to improve ones Territorys efficiency and strength. I cant guarantee how it will affect you but one thing is for sure. I am really happy with my fuel economy and will buy a different territory and deploy all this stuff once again.
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Cheers Jas
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