AGEING. mTOR, rapamycine and calorie restriction.

i just read an article in Scientific American on ageing and developments in creating an antiageing drug and thought id share my thoughts on it. i have an aversion and a great suspicion about concentrating scientific exploration around "curing" everything with drugs plus i have been interested in antiageing info for a while and have been following up on it as often as newer info pops up. i think its already common knowledge, at least in circles imbued in nutrition sciences, that calorie restriction is sofar the only and best way to extend human life. why it is so has been clearing up during the past ten years. the most interesting research has been concentrating on evolutionary theories (my favourite) about the so-called "two-faced" genes that express for cell proliferation and growth and are useful in childhood through to reproduction but after that their purpose kinda swiches - and they age you instead. the thing is, evolutionarily speaking, nature doesnt care how long we live, or what the "quality" of those later years are (our healthspan). evolution just needs us to reproduce. some years ago, due to a cancer in the family, i started to read up on cancer genetics (causes of cell proliferation) and stumbled upon Mikhail Blagosklonny`s research. strangely his article also popped up in the Scientific American article i just read. he talks about a protein mTOR and its effects on the growth of human cells and ageing. mTOR is a protein that is a product of a "two-faced" gene. its production increases when there's plenty of food around in the human system and through pathways that also trigger insulin and IGF (insulin like growth-factor), it prompts cell-proliferation and inhibits autophagy (recycling of dead and damaged cell-components and proteins). that is positive when you are still a growing organism. not so for an adult. too much mTOR can induce insulin resistance, cause unwanted cell growth and promote cellsenesence (a cell grows to abnormal proportions and becomes toxic to its neighbours). when food is scarce the scenario is reversed - mTOR is inhibited, cell growth slows, autophagy is vamped up - ageing slows as a result.

the article i read dismissed calorie restriction for humans as something that is hard to achieve for most mortals and concentrated on rapamycin - a promising new antiaging drug (a fungal inhibitor that has been used in cancer treatments due to its function in inhibiting growth of tumor cells) that works by inhibiting mTOR. the drug added a phenomenal 38 5 to female labmice life-expectancy (and 28% to the males`). the problem is its side effects - it is an immunosuppressant and therefore its longtime use could lead to toxicity. towards the end of the article the author suggests metformin ( a widely used diabetes drug) as a possible candidate for a miricle antiageing agent - as it also inhibits the mTOR pathway in humans.

it is all fine and dandy and definitely intriguing as hell. and just as annoying for me as a hard-boiled IF proponent. to just discard the one and proven way to slow the ageing process as unattainable for us mortals because of what.... we dont have enough willpower to stop gorging ourselves so we need a pill to fix everything. its the same with diabetes treatment - eat anything you want, just inject enough insulin. anybody thats suggests otherwise (as in dich the carbs) and dares to write about it might just get sued in this country (Finland). ofcourse the possibility of intermittent fasting to achieve the necessary 30% cut in calories to achieve the desired mTOR inhibiting effect has never been discussed. i doubt it has ever passed a scientists mind - or atleast the publication-bravery threshold. and different  macronutrients effect on mTOR wasn't even mentioned in the article. for example, we know that a high protein diet has its activating effects on mTOR because the aminoacid leucine promotes the activation mTOR and therefore allows for increased protein synthesis in skeletal muscle (greatly desired by bodibuilders). leucine also promotes gluconeogenesis and aids in the retention of lean mass in a fasted state  (is that such a bad thing)?

what would happen to mTOR regulation and human ageing if a lowcarb diet (i advocate moderate protein) and IF would be combined? on one hand promoting mTOR to keep lean muscle mass and on the other ramping up autophagy during the fasting periods and adding to healthy longevity?? anybody here got funds to study that id greatly appreciate it.

calories in = calories out = unnecessary torture

http://www.nytimes.com/2012/01/01/magazine/tara-parker-pope-fat-trap.html?pagewanted=1&_r=1

i stumbled upon this article today, again, its been all over facebook. but now it was quoted on a blog i like and respect and i read it. it was monstrous (both literally and figuratively speaking). it left a very miserable and anxiety inducing impression.

some months ago i wrote how i feel about the calorie is a calorie theory (i feel its nonsense of a highest grade). and this article shows how true that is. the story of a woman, Janice Bridge, in this article is such a horror story. I mean a woman maintains her 135 lbs weightloss (her current weight is still 195lbs) by measuring every gram she eats, counting every minute of exercise she does. a quote from the article:

She has decided to try to maintain this higher weight of 195, which is still 135 pounds fewer than her heaviest weight.
“It doesn’t take a lot of variance from my current maintenance for me to pop on another two or three pounds,” she says. “It’s been a real struggle to stay at this weight, but it’s worth it, it’s good for me, it makes me feel better. But my body would put on weight almost instantaneously if I ever let up.”
So she never lets up. Since October 2006 she has weighed herself every morning and recorded the result in a weight diary. She even carries a scale with her when she travels. In the past six years, she made only one exception to this routine: a two-week, no-weigh vacation in Hawaii.
She also weighs everything in the kitchen. She knows that lettuce is about 5 calories a cup, while flour is about 400. If she goes out to dinner, she conducts a Web search first to look at the menu and calculate calories to help her decide what to order. She avoids anything with sugar or white flour, which she calls her “gateway drugs” for cravings and overeating. She has also found that drinking copious amounts of water seems to help; she carries a 20-ounce water bottle and fills it five times a day. She writes down everything she eats. At night, she transfers all the information to an electronic record.

the woman is 66, she has had a lifetime full of dieting since she was 14. and when she adheres to the lowfat diet she was put on but didnt lose weight she was accused of cheating:

“No one would believe me that I was doing everything I was told,” she says. “You can imagine how tremendously depressing it was and what a feeling of rebellion and anger was building up.”

sounds familiar much??

i cant even begin to explain how bad i feel for this lady. she has endured this shit all her life. what for???

my feelings are so conflicting. a part of me sees my own mum in her (even though she has no weight issues - not really maybe a 10 lbs extra), im just a softy when it comes to older ladies. a part of me wants me to give her a swift kick in the arse and yell at her something along the lines of :" so calorie counting and lofat hasnt worked since you were 14... but you keep at it religiously??? what does that make you??? maybe you deserve the hell of caloriecounting you call life."

headbangfacepalm

a new workout schedule, new vibrams, a new year :)

so ive been busy or actually lazy - depends on point of view i guess. all of my free time has been consumed by Steven Kings " The Stand" - a classic ive been rereading.

i noticed ive been stuck in a rut at the gym - not because of boredom, but because i was too much in love with my program - having too much fun to notice that the gains were definitely slowing down. so i got a grip and came up with a new program starting 01.01.2012:


its a 2 day split done twice a week - the first round it is a pure strength program with 4 x 6-8 and the second time around it will be a volumeworkout.

so  for day 1 on the 02 of jan i did:
warmup for deadlifting: ham and glute raises 3 x 25 + hip thrusts with a 25 kg plate 3 x 15 with a 1/5/1 tempo

SLDL: a warmup set with 60kg 15 reps and the 5 x 6 with 70/80/85 kg
goblet squats: 25 kg kettlebell 5 x 8
back extentions 4 x 8 with a 25 kg plate
db benchpress: 4 x 8/6 18,5 kg dbs
incline benchpress: same set and weights
dips: 3 x max
narrow bench: 4 x 8/6 40kg
french press: 3 x 8 30 kg
cable pushdowns: 3 x 8
ab wheels 3 x max and 3 x max planks

day 2 on the 03.01 was the following:
pullups: 3 x max with 5 kg added
bb rows: 4 x 8/6 70kg
single hand rows: 4 x 8 28,5 kg dbs
pullovers: 3 x 8 23,5 kg
military press: 3 x 8 30 kg
delt rows: same sets and weight
single arm OHP: 4 x 8/6 13,5kg db
lateral raises: 4 x 8 13,5 dbs
bentover raises: same sets and weight
EZbar curls: 4 x 8/6 28,5 kg
alternating supinated db curls: 3 x 8 11 kg dbs
hanging kneeraises and weighted crunches for abs

the plan is to do the same workouts for volume the same week doing 4 x 15. and i think ill fit in a kettlebellday in the week somewhere. sounds like a plan.

Tomorrow i should get my new fivefinger speeds in the mail - ive been waiting for those for quite some time. cant wait to try them out. enough for now  - gotta hit the gym :)

UPDATE:

in the Helsinki Sanomat newspaper yesterday (a 5 x 5 cm small column somewhere on page gazillion - hey but its better than nothing): a socialwork official was outraged by what is going on and says that it is against the law to take away children on basis of nutritional preference unless there are serious health conditions involved.

the first thought that popped into my mind: so they dont think that morbidly obese toddlers are sick as theres been no cases for taking them away from their families yet (in this country`s media atleast).... i know i know... im just still mad.

just to counter the bullshit thats been going on around here.

we know that calorierestriction is a surefire way to lifeextention, but who wants to starve themselves when theres a better way - just cutting your carbs. ofcourse Dr. Rosedale has been saying that for what.... 20 years now....

http://www.dailymail.co.uk/health/article-1323758/Can-cutting-Carbohydrates-diet-make-live-longer.html

Lowcarb families are threatened by the government in finland: kids whos familes eat lowcarb are now at risk of being removed from their parents.

yes, you read that right. i have been in total rage for a few days after this news came out, so i looked into the backgrounds of this story:

who are these gods that make such decisions or suggestions?

2 names came up - a professor M. Uusitupa and a nutritionist U. Schwab who works directly under the said professor (pun intended? noooo way). i thought id look up their sponsors and heres the list :

Fazer Bakeries Oy, VAASAN bakeries Oy, Raisio Oyj (vegetable oil industry), Raisio Benecol Ltd (vegetable oil industry), Danisco Ltd (sugar industry), International Council of Olive Oil, Arla Foods (lowfat dairy products), Carlshamn Mejeri AB, Svenska Nestlé AB, Van den Bergh Foods AB, Eridania Beghin-Say, Meadow Lea Foods, F Hoffman-La Roche Ltd, Novo Nordisk Foundation.

the proffessor owns stock in the following: 

Orion (pharmacology) and Foodfiles Ltd


What is this Foodfiles???


the company produces customised "research" articles for food- and pharmacology companies. the company openly says that the client can make the decision about publication. they have made a bit over 5 million in the past 4 years. the said professor owns 13% of stock. their clients include:



Arla Foods Ab, AstraZeneca Oy (pharmacology), Atria Oyj (processed tvdinners) , Camelina Oy (rapeseed oil), Danisco Sugar Oy, Oy Karl Fazer Ab (chocolate, desserts), Oy Marli Ltd (juices), Novartis Finland Oy, Oriola Oy, Pouttu Oy (processed meatproducts) ja Valio Oy (lowfat milkproducts).


Uusitupa in the chairman of the local AHA and has taken financial support from:

Boehringer Ingelheim Finland ky, HK Ruokatalo Oy, Medtronic Finland Oy, MSD Finland Oy, Normomedical Oy/Omron Healthcare, Oriola, Orion Corporation Orion Pharma, Oy Eli Lilly Finland Ab, Pfizer, Saarioinen Oy, Sanofi-aventis Oy, Unilever Finland Oy, Vaasan Oy, Valio Oy.
source






he has also sat on the boards of the Danisco researchorganization and the foundation of diabetesresearch at the same time as the foundation has designated him substantial researchallowances. he has also received lecturingfees from Unilever Oy ,a vegetablefat giant.


so you get the idea right?

the good professor spews such nonsense as the CWBS satfat cloggs arteries and cholesterol causes heartattacks that he seems stuck in the 60s. and thats exactly what he is doing - he has on several occasions quoted studies that were made in the 60s and one in particular that was already claimed a false study also in the 60s. - the Finnish Mental Hospital Study. he has also quoted the rabbit studie to prove that a diet of fat and protein causes labanimals cholesterol. i mean really???? feed a lion salad for a year and you have a dead lion - i will not go around and accuse the salad. i will accuse the dimwit "scientist".
he has also professed that wholegrains are slow carbs... i guesse he missed the part in the GItable (pointless on its own i know) where you  have wholemeal bread at 69 and a snickers bar at 40....


at the same time the studies that he falls back on in his lectures and interviews dont back his views at all: some extracts from references used in his article defending the lowfat religion in Suomen Lääkärilehti 37/2011, vsk 66, 2659-2664>>>>


"Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions." source 1

"Successful weight loss can be achieved with either a low-fat or low-carbohydrate diet when coupled with behavioral treatment. A low-carbohydrate diet is associated with favorable changes in cardiovascular disease risk factors at 2 years." source 2

"Compared with the LF group, the LC group had greater decreases in triglycerides, increases in HDL cholesterol and LDL cholesterol" (LDL:n partikkelijakauma on siis parantunut) source 3

"During active weight loss, serum triglyceride levels decreased more and high-density lipoprotein cholesterol level increased more with the low-carbohydrate diet than with the low-fat diet." source 4

"For persons on the low-carbohydrate diet, triglyceride levels decreased more and high-density lipoprotein cholesterol levels decreased less. As seen in the small group of persons with diabetes and after adjustment for covariates, hemoglobin A1c levels improved more for persons on the low-carbohydrate diet. These more favorable metabolic responses to a low-carbohydrate diet remained significant after adjustment for weight loss differences." source5

"In this study, premenopausal overweight and obese women assigned to follow the Atkins diet, which had the lowest carbohydrate intake, lost more weight at 12 months than women assigned to follow the Zone diet, and had experienced comparable or more favorable metabolic effects than those assigned to the Zone, Ornish, or LEARN diets" source6

"Despite favourable effects of both diets on weight loss, the carbohydrate-reduced diet was more beneficial with respect to cardiovascular risk factors compared to the fat-reduced diet." source7

"The low-carbohydrate diet was associated with a greater improvement in some risk factors for coronary heart disease." source 8

"the low-carbohydrate diet produced a greater increase in HDL cholesterol" source 9

"There were significant differences between the groups for weight, high-density lipoprotein cholesterol, triacylglycerols and systolic blood pressure, favouring the low-carbohydrate diet." source10

"Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet, with a relative improvement in insulin sensitivity and triglyceride levels, even after adjustment for the amount of weight lost." source11

(the extracted info here and some info about the professors interviews is quoted from http://vahahiilihydraattinen-ruokavalio-vhh.blogspot.com/2011/10/matti-uusitupa-ja-karppauksen.html)

so the professor is either simply dumb or he is so lazy that he cant be bothered to read the research that he uses. or he is simply so arrogant that he thinks his readers will not read the studies he links to??? Id say all the above.

the butt issue to be continued; nutrition and your ass

im shure most of the readers of this blog, or dare i say all, are down with primal/paleo eating. so im not going to waste space by getting into the no grains/lowfat dairy/legumes/too much fructose mantra and endorsment of MEAT OF ALL KIND :)

lets just say that even though we might work out to the max and eat clean paleo there might still be some wonderment among us women about why oh why is there still junk on our derrieres. a girl might display a fullon sixpack coupled with a jiggly (i mean overly jiggly - some jiggle is hot and needs to stay) lower section. so what gives? there are a few points to discuss here so lets start with the overly obvious:

estrogen:

estrogen is fine and good and necessary for us girls (and even to you guys) but in its normal amounts. this industrialised world and SAD are giving us an overload, though.
i already gave soy the oneover just a couple of days back, so let me just say that soy in everything and anything nowadays is contributing highly to the excess estrogen problem. we also have chemicals (certain herbicides) on our veggies, hormones in our CAFO meat, plastic that we use to store our food in (yes even the BPA-free ones) that all contribute to give us a significant overload of estrogen. so what do you do?
- go organic and avoid ALL processed food
- avoid estrogen-triggering plants like those that are high in diosgenin and B-sitosterol (soy, yams, some traceamounts are found in most roots); estrone or estriol (liquorice, hops, apples, green beans, grains); isoflavones with estrogenic activity (most legumes belong here).
- avoid CAFO meat 
- avoid plastic containers for your food or drink
- consume testosterone boosting foods: YAY FOR FAT AND GRASSFED/FREERANGE MEAT AND EGGS, also some veg have such properties - for example garlic, tumeric, oregano, thyme, rosmary, sage, onion, celery, radish, almonds, pine nuts, stinging nettle and ginseng can be potent androgens. there has been some research indicating some plants to have estrogen-balancing properties: broccoli and all vruciferous plants (although needs to be avoided if there is any doubt about thyroid function), cabbage, omega 3 oil, citrus fruits, CLA, coffee and tea for example.
- some plant extracts block the aromatase enzyme that is used in estrogen formation in our bodies: chrysin from passion flower, apigenine from chamomile, indoles from cabbage, resveratrol, quercetine (onions, garlic), cycads, cactus flower extract, epilobium plants, oenothein A and even vitamin C. so consider taking some of these as supplements. research has proven chrysine, cactus flowers, cycades, yohimbine bark and oenothein A to be most potent aromatase inhibitors.
- also it would be good to give your liver some downtime and aid with milkthiste, dandelion root and ginger and by cutting the alc for a while. excessive alcohol consumption blocks the liver enzyme that breaks down estrogen.




OK, lets say that you are doing everything you can do to cut extra estrogen out of your life but you would like to go from a normal feminine butt to a tight fitnesschick derriere (which means goin lets say from 15% bf to 12% ors mth). when fatloss goals get to that stage, there are a couple of things to consider: in the end, when hormones are in tune, fat cells are fat cells and they just do their jobs. what is essentially different in the fatcells us girls have in our buttocks and thighs, is their adrenoreceptor distribution and bloodflow. adrenoceptors control fat cell metabolism and blood flow into and out of the fat cell. adrenaline and noradrenalin bind to these receptors and give out a signal to either expend free fatty acids or hold on to them. there are two kinds of adrenoreceptors on our fat cells. beta - and alpha receptors (these do have subclasses: alpha 1 and 2 ; beta 1, 2 and 3 but only alpha-2 and beta-2 interest us). beta-receptors release fat for energy use - increase lipolysis - and also increase blood flow in and out of adipose tissue and alpha-receptors inhibit those processes. we women have about 10 times more alpha- that betareceptors in our ass and thigh fat cells. plus, the lower body adipocytes are profoundly insulinsensitive, so any insulinproblems you have will show up on your hips. so here is some advice:

- aerobic exercise stimulates beta fat cells to release fat for use as energy. the best policy would be to either do your cardio fasted to maximise insulinesensitivity or to end an HIIT session with a steadystate one, in order to avoid the possibility of freed fatty acids in your blood being redeposited back on your butt.

- lean muscle mass increases insulin sensitivity, so keep up the good work

- increase your testosterone and growth hormone with supplements, weightlifting, HIIT and IFing

- carb-restriction and high fat diets inhibit the alpha-receptors and ofcourse increase insulin sensitivity

http://www.ncbi.nlm.nih.gov/pubmed/11889199
http://www.ncbi.nlm.nih.gov/pubmed/10516247