High protein diet not as bad for you as smoking

Reposted, without modification from: http://www.nhs.uk/news/2014/03March/Pages/high-protein-diet-may-be-harmful-for-middle-aged.aspx

crabsallover highlights, key points, comments / links.

For me, the message from this research is that "low protein intake during middle age followed by moderate to high protein consumption in older adults may optimise health and longevity." 

From my other IGF-1 posts they seem to me to indicate to me that low IGF-1 levels are implicated in a long, healthy life. IGF-I (wikipedia).

Interesting comments to the Levine et al paper particularly from Jason Cholewa about high protein and body building.

NHS.uk Choices

“People who eat diets rich in animal protein carry similar cancer risk to those who smoke 20 cigarettes each day,” reports The Daily Telegraph.

We have decades of very good evidence that smoking kills and – fortunately for meat lovers – this latest unhelpful comparison with high protein diets largely appears to be a triumph of PR spin.

The warning was raised in a press release about a large study which found that for people aged 50-65, eating a lot of protein was associated with an increased risk of dying.

However, the study, which assessed the diets of Americans in a single 24-hour period (rather than long-term), found in those aged over 65 that a high protein diet was actually associated with a reduced risk of death from any cause or from cancer. These differing findings meant that overall there was no increase in risk of death, or from dying of cancer with a high protein diet.

How much protein should I eat?
In this study, on average people ate 51% of their calories in the form of carbohydrates, 33% as fat and 16% as protein (11% animal protein). This is likely to be higher in fat and lower in carbohydrates than that recommended on the “Eatwell Plate” which shows the relative proportions of food that we should aim to eat.

There are several reasons to be cautious when interpreting the results of this study, including that the researchers did not take into account important factors such as physical activity in their study.

The claim in much of the media, that a high protein diet in middle-aged people is “as dangerous as smoking” is unsupported. We need to eat protein, we do not need to smoke.

Where did the story come from?

The study was carried out by researchers from the University of Southern California (USC) and other research centres in the US and Italy. It was funded by US National Institutes of Health, National Institute on Aging, and the USC Norris Cancer Center. The study was published in the peer-reviewed journal Cell Metabolism and has been made available on an open access basis to read for free.

In general, reporting of the results of the study was reasonable. However, the prominence given to the story (which featured as a front page lead in The Daily Telegraph and The Guardian) in the UK media seems disproportionate.

The headlines suggesting a high protein diet is “as harmful as smoking” was not a specific finding of the study and could be seen as unnecessary fear-mongering. This is particularly of note given that the effects of a high protein diet were found to differ dramatically by age.

To be fair to the UK’s journalists, this comparison was raised in a press release, issued by the University of Southern California. Unfortunately this PR hype appears to have been taken at face value.

What kind of research was this?

This study looked at the relationship between the amount of protein consumed and subsequent risk of death among middle aged and older adults. It used data collected in a previous cross-sectional study and information from a national register of deaths in the US.

While the data used allowed researchers to identify what happened to people over time, this wasn’t the original purpose of the data collection. This means that some information on what happened to people may be missing, as researchers had to rely on national records rather than keeping close track of the individuals as part of the study.

What did the research involve?

The researchers had data on protein consumption for 6,381 US adults aged 50 and over (average age 65). They then identified which of these people died over the following 18 years (up to 2006) using national records. The researchers carried out analyses to see whether people who ate more protein in their diets were more likely to die in this period than those who ate less protein.

The information on protein consumption was collected as part the third National Health and Nutrition Examination Survey (NHANES). These surveys are designed to assess the health and nutritional status of people in the US. The participants are selected to be representative of the general US population. As part of the survey they reported their food and drink intake over the past 24 hours using a computerised system. The system then calculated how much of different nutrients they consumed.

Each person’s level of protein consumption was calculated as the proportion of calories consumed from protein. Protein intake was classed as:
High – 20% or more of calories from protein (1,146 people)
Moderate – 10 to 19% of calories from protein (4,798 people)
Low – less than 10% of calories from protein (437 people)

The researchers used the US National Death Index to identify any of the survey participants who died up to 2006, and the recorded cause of death. The researchers looked at whether proportion of calories consumed from protein was related to risk of death overall, or from specific causes. As well as overall deaths, they were also interested in deaths specifically from cardiovascular disease, cancer, or diabetes.

The researchers also looked at whether the relationship differed in people aged 50-65 years, and older individuals, and whether it was influenced by fat, carbohydrate or animal protein intake.

The analyses took into account factors (confounders) that could influence the results, including:

• age
• ethnicity
• education
• gender
• "disease status"
• smoking history
• participants’ dietary changes in the last year
• participants’ attempted weight loss in the last year
• total calorie consumption

The researchers also carried out studies to look at the effect of protein and their building blocks (amino acids) in yeast and mice.

What were the basic results?

On average, the participants consumed 1,823 calories over the day:

• 51% from carbohydrates
• 33% from fat
• 16% from protein (11% from animal protein).

Over 18 years, 40% of participants died; 19% died from cardiovascular diseases, 10% died from cancer, and about 1% died from diabetes.

Overall, there was no association between protein intake and risk of death from any cause, or death from cardiovascular disease or cancer. However, moderate or high protein consumption was associated with an increased risk of death related to complications associated with diabetes.

The authors noted that the number of people dying from diabetes-related causes was low, so larger studies were needed to confirm this finding.

The researchers found that results for death from any cause and from cancer seemed to vary with age. Among those aged 50-65, those who ate a high protein diet were 74% more likely to die during follow up than those who ate a low protein diet (hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.02 to 2.97).

People in this age group who ate a high protein diet were more than four times as likely to die from cancer during follow up than those who ate a low protein diet (HR 4.33, 95% CI 1.96 to 9.56).

The results were similar once the researchers took into account the proportion of calories consumed from fat and carbohydrates. Further analyses suggested that animal protein was responsible for a considerable part of this relationship, particularly for death from any cause.

However, the opposite effect of high protein intake was seen among those aged over 65. In this age group high protein intake was associated with:

• a 28% reduction in the risk of death during follow up (HR 0.72, 95% CI 0.55 to 0.94)
• a 60% reduction in the risk of death from cancer during follow up (HR 0.40, 95% CI 0.23 to 0.71)

How did the researchers interpret the results?

The researchers concluded that low protein intake during middle age followed by moderate to high protein consumption in older adults may optimise health and longevity.

Conclusion

This study has found a link between high protein intake and increased risk of death among people aged 50-65, but not older adults. There are some important points to bear in mind when thinking about these results:
The human data used was not specifically collected for the purpose of the current study. This meant that the researchers had to rely on the completeness of, for example, national data on deaths and causes of death. This may mean that deaths of some participants may have been missed.

Information on food intake was only collected for one 24-hour period, and this may not be representative of what people ate over time. Most people (93%) reported that it was typical of their diet at the time, but this may have changed over the 18 years of follow up.

The researchers took into account some factors that could affect results, but not others, such as physical activity.

Although the study was reasonably large, numbers in some comparisons were relatively low, for example, there were not many diabetes-related deaths and only 437 people overall ate a low protein diet. The broad confidence intervals for some of the results reflect this.

Many news sources have suggested that a high protein diet is “as bad for you” as smoking. This is not a comparison that is made in the research paper, therefore its basis is unclear. While we do need some protein in our diets, we don’t need to smoke, so this is not a helpful comparison.

While the authors suggested that people eat a low protein diet in middle age and switch to a high protein diet once they get older, it is not possible to say from the study whether this is what the older participants actually did, as their diets were only assessed once.

Ideally the findings need to be confirmed in other studies set up to specifically address the effects of higher protein diets, particularly the strikingly different results for different age groups.

While certain diet plans, such as the Atkins diet or the “caveman diet” have promoted the idea of eating a high-protein diet for weight loss, relying on a single type of energy source in your diet is probably not a good idea. Consumption of some high-protein foods such as red meat and processed meat is already known to be associated with increased risk of bowel cancer.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links to the headlines

High-protein diet 'as bad for health as smoking'. The Daily Telegraph, March 4 2014
Diets high in meat, eggs and dairy could be as harmful to health as smoking. The Guardian, March 4 2014
Eating too much meat and eggs is ‘just as bad as smoking’, claim scientists. The Independent, March 4 2014
Eating lots of meat and cheese in middle age is 'as deadly as SMOKING'. Daily Mail, March 4 2014
Eating lots of meat and cheese could be as bad for you as smoking, report reveals. Daily Mirror, March 4 2014
Meat And Cheese 'As Bad For You As Smoking'. Sky News, March 4 2014

Links to the science

Levine ME, Suarez JA, Brandhorst S, et al. Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population. Cell Metabolism. Published online March 4 2014. (Open Access = FREE!)

Further reading

Press release
University of Southern California. Meat and cheese may be as bad as smoking. Published March 5 2013

Results from Paper
I've copied the Highlights and Summary from the paper.

Authors: Morgan E. Levine, Jorge A. Suarez, Sebastian Brandhorst, Priya Balasubramanian, Chia-Wei Cheng, Federica Madia, Luigi Fontana, Mario G. Mirisola, Jaime Guevara-Aguirre, Junxiang Wan, Giuseppe Passarino, Brian K. Kennedy, Min Wei, Pinchas Cohen, Eileen M. Crimmins, Valter D. Longo

Highlights

• High protein intake is linked to increased cancer, diabetes, and overall mortality
• High IGF-1 levels increased the relationship between mortality and high protein
• Higher protein consumption may be protective for older adults
• Plant-derived proteins are associated with lower mortality than animal-derived proteins

Summary

Mice and humans with growth hormone receptor/IGF-1 deficiencies display major reductions in age-related diseases. Because protein restriction reduces GHR-IGF-1 activity, we examined links between protein intake and mortality. Respondents aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years. These associations were either abolished or attenuated if the proteins were plant derived. Conversely, high protein intake was associated with reduced cancer and overall mortality in respondents over 65, but a 5-fold increase in diabetes mortality across all ages. Mouse studies confirmed the effect of high protein intake and GHR-IGF-1 signaling on the incidence and progression of breast and melanoma tumors, but also the detrimental effects of a low protein diet in the very old. These results suggest that low protein intake during middle age followed by moderate to high protein consumption in old adults may optimize healthspan and longevity.

IGF-1 available from Nuffield Hospitals for £97

Paul Harris (Medical Director) at Blue Horizon Medicals advises IGF-1 test costs £57 + £39.95 medical fee at Bournemouth Nuffield Hospital.

Dr. Krista Varady Interviewed on Alternate Day Fasting

Dr Krista Varady

reposted from: http://www.healthyfellow.com/511/alternate-day-fasting-interview-part-1/
April 7, 2010 Written by JP - The Health Fellow

crabsallover highlights, key points, comments / links.

Krista Varady research into Alternate Day Fasting (ADF) is at the very early stages with low trial numbers. Further research is needed using much larger RCTs. The theory is that ADF mimics our hunter-gatherer evolutionary past when feasting was followed by periods of famine. 


JP: Is it fair to say that you believe that the actual practice of prolonged fasting may impart added benefits beyond that of just reducing calories on alternate days?
Dr. Varady: That’s another study I want to design to see if we actually see different effects if we compare people on alternate day fasts that are consuming their meals within that amount of time (12:00 – 2:00) compared to people that are allowed to eat throughout the day. I think that if we did do that study, we’d actually see better effects from people doing the confined eating period. I think our bodies are used to that from the hunter-gatherer days where we’d have days of plenty where we could eat a bunch and then all of a sudden there was nothing out there and we’d have to fast. So I think our bodies are capable of doing that.


JP: How long does it generally take for people to adapt to this new way of eating?
Dr. Varady: A lot of the subjects were saying that for the first two weeks it was pretty tough to basically change from a 3 meal a day eating pattern to just eating 1 meal a day and then 3 slightly bigger meals the next day. But they said that about after two weeks they totally got used to it and weren’t that hungry on the fast day anymore. They could undergo these really long periods of fasting without really feeling deprived. The other interesting thing that they were telling us was with regard to the feed day. The people didn’t binge. They only ate about 100% to 110% of their calorie needs.

Research
http://www.nature.com/oby/journal/vaop/ncurrent/pdf/oby201054a.pdf
Abstract

The ability of alternate-day fasting (ADF) to modulate adipocyte parameters in a way that is protective against coronary heart disease (CHD) has yet to be tested. Accordingly, we examined the effects of ADF on adipokine profile, body composition, and CHD risk indicators in obese adults. Sixteen obese subjects (12 women/4 men) participated in a 10-week trial with three consecutive dietary intervention phases: (i) 2-week baseline control phase, (ii) 4-week ADF controlled feeding phase, and (iii) 4-week ADF self-selected feeding phase. After 8 weeks of treatment, body weight
and waist circumference were reduced (P < 0.05) by 5.7 ± 0.9 kg, and 4.0 ± 0.9 cm, respectively. Fat mass decreased (P < 0.05) by 5.4 ± 0.8 kg, whereas fat-free mass did not change. Plasma adiponectin was augmented (P < 0.05) by 30% from baseline. Leptin and resistin concentrations were reduced (P < 0.05) by 21 and 23%, respectively, post‑treatment. Low-density lipoprotein cholesterol (LDL-C) and triacylglycerol concentrations were 25% and 32% lower (P < 0.05), respectively, after 8 weeks of ADF. High-density lipoprotein cholesterol (HDL-C), C-reactive protein, and homocysteine concentrations did not change. Decreases in LDL-C were related to increased adiponectin (r = −0.61, P = 0.01) and reduced waist circumference (r = 0.39, P = 0.04). Lower triacylglycerol concentrations were associated with augmented adiponectin (r = −0.39, P = 0.04) and reduced leptin concentrations (r = 0.45, P = 0.03) post-treatment. These findings suggest that adipose tissue parameters may play an important role in mediating the cardioprotective effects of ADF in obese humans.


http://www.healthyfellow.com/517/dr-krista-varady-interview-part-2/ - Interview 2 by Healthy Fellow



JP: I’m fascinated with the role that blood sugar control and insulin sensitivity play in various aspects of health. Does ADF have any significant impact on how the body manages blood sugar and insulin levels?
Dr. Varady: Beyond the weight loss, fasting might play a role in that. You’re not having food come into your body. Therefore you’re not having insulin released by your pancreas. So really you’re having this time where there shouldn’t be much insulin circulating around in your body, which is a good thing because insulin is lipogenic. So it basically causes your fat to be stored and not broken down. It also interacts with certain growth hormones – IGF (insulin-like growth factor) for one, which is related to growth hormone. And that can actually stimulate cell proliferation. So insulin does play a role potentially in cancer risk.


JP: Many people are interested in learning about natural ways of slowing down the aging process. Is ADF a good candidate in this arena?
Dr. Varady: If you have a diet that will slow the rate of cell turnover that’s actually slowing aging technically. I think there’s definitely going to be more data coming out regarding that. I guess after we do most of these weight loss and heart disease efficacy trials, I’d also be interested at looking at the aging process as well

On Calorie Restriction, Monkeys, Magic and Medicine

Science Writer David Stipp RSS Feed highlighted new research on Calorie Restriction in Monkeys published this week in Nature (ref 4).

1) On Calorie Restriction, Monkeys, Magic and Medicine - Compares to Wisconsin 2009 study. David Stipp comment 'CR hasn’t extended lifespan in all species, nor has it worked in certain strains of rodents. In the latest study on the topic, it failed to extend lifespan in a long-term study in rhesus monkeys at the National Institute on Aging (NIA)....the study suggested that CR improved late-life health in the monkeys, but the effect was modest and gender-specific.... dietary factors potentially gave a boost to the NIA controls’ health as they aged, which might have contributed to the fact that they were about as healthy and long-lived as the monkeys on CR in the study '

2) http://www.nature.com/news/calorie-restriction-falters-in-the-long-run-1.11297#/b1 - Nature staff writer comment 'Calorie restriction falters in the long run - Genetics and healthy diets matter more for longevity.'

3) http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11484.html - Steve Austad comment

4) http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11432.html - Nature Journal primary research.

5) http://www.nydailynews.com/life-style/health/low-calorie-diet-prolong-life-study-article-1.1148839 NY Daily News

6) http://www.wired.co.uk/news/archive/2012-08/30/calorie-restriction-diets - Luigi Fontana comments that possibly no effect of CR seen because monkeys were all on high protein diets. In humans, those hormones decrease only when protein intake is dramatically reduced. It's not enough to cut calories alone. "It's possible that we don't see some of the beneficial effects of longevity in these monkeys because they were on a high-protein diet," Fontana said. "The old idea is that a calorie is a calorie. When you restrict it, you have a beneficial effect. Our data and other data suggests this isn't the case. The quality of the diet matters," Fontana continued.

7) http://www.newscientist.com/article/dn22231-eating-less-fails-to-extend-monkey-lives.html Luigi Fontana believes both studies should have paid more attention to dietary composition. "Fifteen per cent of the monkey diet came from protein – that's too much," he says. "Our work suggests lowering protein, rather than calories, may be the key to increasing longevity – so reducing protein intake could have led to better results." De Campo agrees that dietary composition might play a role in lengthening life, but claims the benefits of calorie restriction are still strong. "Although we don't have the same lifespan findings as the Wisconsin group, what's really important is that we did show similar improvements in health."

8) http://www.theiflife.com/calorie-restriction-does-not-promote-longevity/ Intermittent Fasting website. Talk about lower IGF-1 levels with low protein diets.

IGF-1 levels

reposted from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774752/

crabsallover highlights, key points, comments / links.

"Moreover, in monkeys (and by extension, humans) some benefits of dietary restriction, such as low IGF-I levels, may decrease cancer risk, but also increase the risk of osteoporotic fractures 35. Thus, it might be necessary to reduce IGF-I signalling during early adulthood to prevent cancer, but increase it at older ages to prevent non-cancerous diseases 36."

Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models

Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models

reposted from:

crabsallover highlights, key points, comments / links.

"Consistently, two interventions, caloric restriction and repression of the growth hormone (GH)/insulin like growth factor-1/insulin axis, have been shown to increase lifespan in both invertebrates and vertebrate animal model systems. Caloric restriction (CR) is a nutrition intervention that robustly extends lifespan whether it is started early or later in life. Likewise, genes involved in the GH/IGF-1 signaling pathways can lengthen lifespan in vertebrates and invertebrates, implying evolutionary conservation of the molecular mechanisms. Specifically, insulin and insulin-like growth factor 1 (IGF-1)-like signaling and its downstream intracellular signaling molecules have been shown to be associated with lifespan in fruit flies and nematodes. 

More recently, mammalian models with reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have extended lifespans as compared to control siblings. Importantly, this research has also shown that these genetic alterations can keep the animals healthy and disease-free for longer periods and can alleviate specific age-related pathologies similar to what is observed for CR individuals. Thus, these mutations may not only extend lifespan but may also improve healthspan, the general health and quality of life of an organism as it ages.

Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models

Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models

reposted from:

crabsallover highlights, key points, comments / links.

Control of aging and longevity by IGF-I signaling. [Exp Gerontol. 2005] - PubMed - NCBI

Control of aging and longevity by IGF-I signaling. [Exp Gerontol. 2005] - PubMed - NCBI

reposted from:

crabsallover highlights, key points, comments / links.

"Abstract: Animal models have established the IGF-I signaling pathway as a key modulator of aging in rodents and invertebrates. Considerable evidence suggests that reduced exposure of tissue to IGF-I is associated with an extended lifespan in these species.
In humans, IGF-I is linked to various age-related diseases that are limiting factors for youthful longevity. On one hand, reduced IGF-I activity is associated with significant morbidity in adulthood with an increased risk of developing cardiovascular disease, diabetes, osteoporosis and neurodegenerative diseases.
On the other hand, elevated IGF-I levels have been linked to cancer risk given the role of IGF in mediating normal and malignant tissue growth.
Thus, IGF is clearly involved in modulating disease of aging; however, the mechanism appears to be complex and interdependent on additional modulating factors.
It is attractive to hypothesize that maximal human survival depends on tight regulation of the GH-IGF axis and maintenance of optimal IGF-I action in order to prevent morbidities associated with either deficient or excessive state. Specifically, it is possible that lower levels of IGF-I during early adulthood followed by higher levels of IGF-I later in life may be most beneficial for human longevity by addressing age-specific morbidities."

Potentially conserved pro-ageing pathways, their interconnections and possible targets for intervention

PubMed Central, Figure 1: Nature. 2008 August 28; 454(7208): 1065–1071. doi: 10.1038/nature07216 from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774752/

reposted from:

crabsallover highlights, key points, comments / links.

In this very simplified depiction, three main pathways, the IIS (insulin/insulin-like growth factor 1 (IGF-I) signalling) pathway, TOR and mitochondrial pathway, are indicated.

The pro-ageing activities of these pathways are conserved across species, with energy sensors, such as AMPK, as potentially important hubs in the complex networks that integrate them.

However, it is important to note potential dissimilarities among species as well. Most, if not all, defects in the mitochondrial respiratory chain are lethal or cause disease in humans, but can increase lifespan in nematodes or yeast. In mammals, mitochondria play an important part in signalling apoptosis, which can either drive or retard ageing, depending on the cell type.

There is evidence that many longevity signals converge on members of the FOXO and sirtuin protein families, which can interact. Effects of FOXO and SIR2 in cells can be either beneficial (for example, increasing antioxidant defence) or detrimental (for example, apoptosis), and may or may not promote organismal survival. Apoptosis can be beneficial, for example, by eliminating damaged cells and preventing cancer, or can be detrimental, by eliminating irreplaceable cells, such as neurons.

Patrick Holford on Michael Mosley 'Eat, Fast & Live Longer"

reposted from: http://www.patrickholford.com/index.php/blog/blogarticle/1237/

crabsallover highlights, key points, comments / links.

Posted Tuesday, August 07, 2012
Patrick Holford says inter alia ...


Readers of my newsletter, or latest book Ten Secrets of Healthy Ageing will be familiar with the reasons behind the benefits of modified fasting, which lowers blood sugar levels and insulin production. This, in turn, reverses metabolic syndrome and burns fat. The Horizon programme emphasized the need to bring down levels of insulin-like growth factor (IGF-1) to extend life and reduce disease risk. In Issue 55 I explained in detail how IGF-1 is associated with disease risk and, in Issue 61, why it is critical for health to keep insulin down. Horizon recommended eating less protein to bring down IGF-1, but failed to mention that the biggest promoter is dairy products. This is why my low-GL diet, which is specifically designed to keep insulin down, includes very little meat or dairy products.

If your goal is to live long and be healthy it’s better to have lower IGF-1 levels, achieved by eating a more plant-based, less meat and dairy based diet. The key is to keep blood sugar levels stable, which means less insulin release. These are the key principles in my low GL diet.

Emma Rourke reviews Horizon: Eat, Fast, and Live Longer

reposted from: http://blogs.bmj.com/bmj/2012/08/14/emma-rourke-reviews-horizon-eat-fast-and-live-longer/

crabsallover highlights, key points, comments / links.

14 Aug, 12 | by BMJ Group

There’s a new intervention being trialled. It will help you lose weight, it will delay the potential onset of dementia, and best of all it will enable you to live in the fullest of health for longer. Perhaps the main virtues of this intervention centre on its sheer simplicity: it doesn’t involve putting any chemicals into your body, it doesn’t involve surgery, and it doesn’t cost anything—it may even save you money. All you have to do is deprive yourself of one of life’s great pleasures—food.

The BBC aired Horizon: Eat, Fast and Live Longer earlier this week. During this one hour programme, Michael Mosley visits a number of institutions seeking to understand the ageing process. He meets a variety of experts, all of whom extol the virtues of caloric restriction (CR), and tries methods they advise in attempts to improve his performance on physiological testing. The most extreme of these methods involved 3 days and 4 nights of fasting, wherein Mosley consumed only water, black tea, and a single sachet of powdered soup.  Subsequently, he tried alternate day fasting, where consumption is limited to around 500 calories on one “fast” day and completely unlimited the following “feed” day. He finally settled for a 5 day “feed” period followed by a 2 day 500 calorie fast period.

For a supposedly scientific programme, however, the science was rather scant. The focus was strongly on the insulin-like growth factor 1 (IGF-1) as mediator of the benefits of CR. This signalling pathway has been widely studied and is known to stimulate growth and inhibit apoptosis of cells. Perhaps unsurprisingly given this role, it has been implicated in the pathogenesis of cancer [1]. It has several key functions in the body, including growth and maintenance of the skeletal system [2]. Interestingly, in vivo deficiency of IGF-1 in combination with testosterone correlates with reduced survival [3].

CR (without malnutrition) has been shown to increase lifespan in laboratory animals. In rodents, for example, CR postpones onset of age-related pathology and prolongs lifespan [4]. Is this explained solely by IGF-1 levels? Studies have sought to test the popular oxidative stress theory of ageing, and indeed noted reduced markers of oxidative damage in calorie restricted rodents [4]. This alternative mechanism by which CR may affect ageing is not even touched upon by the programme. As with much human science, it is more complicated than it seems and there is still no consensus on the role of antioxidant levels in CR—there’s something else at play [4]. That something may involve the nutrient-sensing pathways of target of rapamycin (TOR), it may involve the forkhead transcription factor (FOXO), and it may involve sirtuins [5]. In fact, the one thing we can be sure about is that the molecular determinants of lifespan are incredibly complex, and far from fully understood [6].

The programme furthermore neglected many social factors complicit in the ageing process. Humans are not laboratory animals and their environment cannot be so strictly controlled. Nevertheless, somewhat controversial experimentation in humans is ongoing. Accordingly, some may question whether it is responsible for a qualified doctor to so emphatically endorse such an approach in a prime time television slot? “This could radically transform the nation’s health,” he says.

The programme was littered with health warnings—“don’t do this without supervision” and “for some fasting can be dangerous”—but within hours online weight loss forums were overflowing with posts from people saying they’d give it a go. Mosley’s wife, a GP, appears to support his desire to pursue a 5 days feeding 2 days fasting regime, thus reinforcing to the public that this is a safe and worthwhile method.

Perhaps the diet Mosley ultimately adopts is not that radical, and perhaps it doesn’t even represent CR (the level at which CR is defined varies from 10-25% reduction in overall calorie intake in humans). Any attempt to encourage reduced calorie intake in a nation with such high rates of obesity as our own may be commendable, but critics will likely find little new in the advice Mosley dishes out: reduce your calorie intake, reduce your weight, reduce your cardiovascular risk factors. Perhaps that’s the message to hope people take forward from this.

References:

[1] Hematol Oncol Clin North Am. 2012 Jun;26(3):527-42, vii-viii. Epub 2012 Feb 28.

[2] J Bone Miner Metab. 2008;26(2):159-64. Epub 2008 Feb 27.

[3] Steroids. 2012 Jan;77(1-2):52-8. Epub 2011 Oct 20.

[4] Mechanisms of Ageing and Development. 2004;125(10-11):811-26.

[5] Nature. 2008;454(7208):1065-71.

[6] Free Radic Biol Med. 2011 Jul 15;51(2):250-6. Epub 2011 Apr 22.

Eat, Fast and Live Longer by BBC Horizon with Michael Mosley

reposted from: http://www.bbc.co.uk/iplayer/episode/b01lxyzc/hd/Horizon_20122013_Eat_Fast_and_Live_Longer/ (view until 17th September 2012) or thereafter on http://documentaryheaven.com/eat-fast-and-live-longer/ (accessed August 21st, 2017)

my comments and links in blue. 

Summary

http://www.bbc.co.uk/news/health-19112549 - BBC

Michael J. Mosley (wikipedia) fasted for two days every week

Michael Mosley says 'Scientists are uncovering evidence that short periods of fasting if properly controlled, could achieve a number of health benefits, as well as potentially helping the overweight.'


The Horizon editor assured me there was great new science and that I might see some dramatic improvements to my body. So, of course, I said, "yes".

I am not strong-willed enough to diet over the long-term, but I am extremely interested in the reasons why eating less might lead to increased life span, particularly as scientists think it may be possible to get the benefits without the pain. 


How you age is powerfully shaped by your genes. But there's not much you can do about that.

Calorie restriction, eating well but not much, is one of the few things that has been shown to extend life expectancy, at least in animals. We've known since the 1930s that mice put on a low-calorie, nutrient-rich diet live far longer. There is mounting evidence that the same is true in monkeys.' Source: BBC

Synopsis

From Start: Taster of this hour long Michael Mosley Horizon programme first broadcast on 6th August 2012.

Fauja Singh

@ 2 minutes: London Marathon - Fauja Singh is 101 years and the oldest marathon runner. Unknowingly he has been testing the reduced calorie diet by eating child size (ie half) portion meals for most of his life.

9m: in 1930s at Cornell University [Clive McCay] showed that mice live longer on a restricted diet

Luigi Fontana

10m: Prof. Luigi Fontana (profile & research papers eg  http://www.ncbi.nlm.nih.gov/pubmed/17482403 & http://ajpendo.physiology.org/content/293/1/E197.long, also http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673798/ & CR Society Research (cited in The Longevity Diet by Brian Delaney and Lisa Walford) of BJC Institute of Health at Washington Uni & Salerno school of medicine studies people on severe calorie restricting diets ('these people look like a new species!') aka CRONies Calorie Restriction with Optimal Nutrition (CRON-Diet Wikipedia). Joe Cordell (twitter) has 11.5% body fat typical of a super athlete, has a 1 in a million chance of CVD (nb. myocardial infarction, stroke or heart failure are responsible for 40% deaths in UK/USA) and eats lots of fruit and veg. He only eats apple skins which have 95% of apple nutrition, the rest of an apple is sugar! Living a healthy lifestyle is fun, claims Joe!

Joe has eaten 1900 calories a day, weighs 134 pounds (cf Mike Mosley 190 pounds, 27% body fat, abdominal fat 30% - not good for his age - higher risk of CVD, stroke, cancer). If Mosley went on Joes Calorie Restriction lifestyle he would be 'cured within a year'.

[There are 100,000 CRONies worldwide (who eat food rich in nutrients but low in calories) I presume members of the CR Society International. CRONies say that body fat content should be 6-9% for men, 10-15% for females (The Anti-Aging Plan: Strategies and Recipes for extending your Healthy years by Lisa and Roy Walford, page 19)].

Valter Longo

Professor Longo has investigated growth hormone deficiency in humans

19m: Prof. Valter Longo, Uni Southern California, LA (profile & example). Experiments with a tiny mouse give 40% increased lifespan (equiv. to 120-year-old human) with genetically engineered low levels of Insulin-like Growth Factor 1 (IGF-1).

'Growth Hormone: The world record for extending life expectancy in a mammal is held by a new type of mouse which can expect to live an extra 40%, equivalent to a human living to 120 or even longer. It has been genetically engineered so its body produces very low levels of a growth hormone called IGF-1, high levels of which seem to lead to accelerated ageing and age-related diseases, while low levels are protective.' source: BBC

A 32-year-old community leader and artist who has the rare dwarfism condition (Laron Syndrome), with his bride, 17.
Source:  http://www.nytimes.com/2011/02/17/science/17longevity.html?_r=2&hpw

21m 45s: Equador - Laron Syndrome (wikipedia) & (research paper) dont get diabetes or cancer (Longo research, Sci Transl Med. 2011 Feb 16;3(70):70ra13) with images in paper.

Michael Mosley says 'Professor Longo has investigated growth hormone deficiency in humans - a similar, but natural, genetic mutation has been found in humans with Laron syndrome, a rare condition that affects fewer than 350 people worldwide. The very low levels of IGF-1 their bodies produce means they are short, but this also seems to protect them against cancer and diabetes, two common age-related diseases.

The IGF-1 hormone (insulin-like growth factor) is one of the drivers which keep our bodies in go-go mode, with cells driven to reproduce. This is fine when you are growing, but not so good later in life. There is now evidence suggesting that IGF-1 levels can be lowered by what you eat. 

Studies on calorie restrictors suggest that eating less helps, but it is not enough. As well as cutting calories you have to cut your protein intake. Not entirely - that would be a very bad idea. It's about sticking to recommended guidelines, something most of us fail to do. The reason seems to be that when our bodies no longer have access to food they switch from "growth mode" to "repair mode". 

As levels of the IGF-1 hormone drop, a number of repair genes appear to get switched on according to ongoing research by Professor Valter Longo of the University of Southern California.' source: BBC

NY Times article: 'physiology of Laron patients links up with the longevity studies that researchers have been pursuing with laboratory animals. IGF-1 is part of an ancient signaling pathway that exists in the laboratory roundworm as well as in people. The gene that makes the receptor for IGF-1 in the roundworm is called DAF-2. And worms in which this gene is knocked out live twice as long as normal.'

The single point mutation produces individuals that have very low levels of the growth hormone IGF-1. (Is IGF-1 hormone reduction good for you?) . Our cells are constantly made to divide by IGF-1 (24m) but with low levels of IGF-1 our body stops making new cells and repairs instead existing cells, DNA damage is more likely to get fixed which is why the mice and the villagers are protected from age-related diseases. High levels of protein make high levels of IGF-1 (the body is in go-go mode) (25m) and body is growing too fast for cancer and diabetes to be repaired. Eating less is not enough (26m) - you also have to cut your protein intake. You don't have to be a CRONe to lower IGF-1. Instead, fasting (plenty of water, black tea & 50 calories Cuppa-soup) for 3.5 days lowers IGF-1 and glucose levels. Michael Morley's IGF level was 210ng/ml before the fast (could increase prostate cancer risk) (33m) (normal range for humans 80-230ng/ml). After 3.5 days fast MM IGF-1 level was 110 ng/ml. MM blood glucose levels 110mg/dl (pre-fast) dropped to 80mg/dl after 4 day fast (34m). But effects will not last unless switch to a lower protein plant based diet and fast once a month to maintain benefits.

IGF-1 levels are tested by LabTestsOnline.

Krista A. Varady

Krista A. Vardy with Michael Mosley

38m: Assistant Prof. Dr Krista A. Varady (profile) the University of Illinois at Chicago. Has done research on Alternate Day Fasting (ADF) which involves 500-600 calories for men (400-500 calories for women) (25% of normal intake) on a fast day. On feed days you could eat 'whatever you want'. This ADF can result in decreased LDL, triglycerides and blood pressure levels. On the feed days, no difference in levels was found among people who had low or high-fat diets (41m). Actual consumption on feed days was only 110% of normal calorie intake (not 175% or a gorge as might be expected!) so, surprisingly, you can really tell people to eat 'whatever you want' [and however much you want] on feed days.

http://www.ajcn.org/content/86/1/7.full - Krista Vardy Review of Intermittent Fasting IF (accessed 13th August 2012) via http://www.huffingtonpost.com/andrew-weil-md/fasting-health_b_1557043.html (accessed 13th August 2012).

Vardy concluded inter alia:-

"both human and animal experiments indicate that Alternate Day Fasting ADF may effectively decrease the risk of CVD, whereas results from animal studies suggest a protective effect on cancer risk. In terms of diabetes prevention, animal data suggest a beneficial effect, but human data have been equivocal. However, it is important to note that the human studies examined in this review are limited; they all lacked control groups and used short trial lengths. Future studies with longer trials and including control groups are needed to answer these important questions.

Moreover, human ADF trials in modestly overweight persons, who are at greater risk of chronic disease, are warranted. In this context, it is important to note that the control animals in both the CR and ADF studies are likely to have been obese because they were fed ad libitum.

ADF regimens also may be as efficacious as daily Calorie Restriction CR in improving certain indexes of the risk of type 2 diabetes and CVD. Further analysis of the mechanisms responsible for beneficial effects of ADF is clearly warranted. Finally, it seems intuitively likely that persons will find it easier to fast or reduce intake on alternate days than to reduce their intake every day. For this reason, ADF regimens may allow better compliance than would CR regimens and may represent an attractive area for investigation.

It will also be important to understand whether the mechanisms by which ADF protects against chronic disease risk are similar to those of CR. Indirect evidence suggests that the 2 regimens may share mechanisms. For instance, the study of Descamps et al (26) reported increases in spleen mitochondrial Superoxide Dismutase (SOD) activity accompanied by decreases in the mitochondrial generation of Reactive Oxygen Species (ROS) as a result of ADF. Such findings suggest that ADF may act by increasing resistance to oxidative insult, which is a key feature of the stress resistance hypothesis.

In summary, this still nascent literature suggests that ADF may effectively modulate metabolic and functional risk factors, thereby preventing or delaying the future occurrence of common chronic diseases, at least in animal models. The effect of ADF on chronic disease risk in normal-weight human subjects remains unclear, however, as do the mechanisms of action. Much work remains to be done to understand this dietary strategy fully."

'Intermittent fasting (IF) (wikipedia)
Michael Mosley says 'One area of current research into diet is Alternate Day fasting (ADF), involving eating what you want one day, then a very restricted diet (fewer than 600 calories) the next, and most surprisingly, it does not seem to matter that much what you eat on non-fast days. Dr. Krista Varady of the University of Illinois at Chicago carried out an eight-week trial comparing two groups of overweight patients on ADF. "If you were sticking to your fast days, then in terms of cardiovascular disease risk, it didn't seem to matter if you were eating a high-fat or low-fat diet on your feed (non-fast) days," she said.' source: BBC

Mark P. Mattson

43m: National Institute of Ageing, Baltimore Mark P. Mattson (profile & papers) - effects of ageing on the brain. Fasting may slow onset of diseases (Alzheimers, dementia and memory loss). Mice on Intermittent Energy Restriction (IER) (Feast / fast) have equivalent to 30 years (in human terms) slower onset of Alzheimer's.

new brain neurons develop when IF regime is followed

Fasting mice have newly born brain neuron cells (46m) which are an evolutionary survival advantage if you are hungry and you can remember where the location of the food source is. Fasting exercises your brain like exercise stretches your muscles. Hunger makes you sharper. Alternate day fasting has a better outcome on the brain than daily Calorie Restriction (at least in mice, but human trials are needed to prove its true in us). Mark P. Mattson recommended MM try a 5:2 diet (48m) (5 days normal & 2 days 600 calories/day fast. Eat anytime (ie breakfast /lunch or breakfast/dinner or lunch/dinner) during the fast day (50m) for 5 weeks to see if get results (49m).

'Science is not belief, but the will to find out' (50m 34s)

5:2 feed:fast trial

In the period of filming (~5+ weeks) Mosley lost over a stone (~190 pounds to 174 pounds), total body fat reduced (27% to 19%) (53m). Luigi Fontana gave 5-week results (54m): IGF-1 reduced by 50% - enough to reduce the risk of prostate and colon cancer, blood sugar was borderline diabetic (110mg/dl) reduced to 90mg/dl (normal), total cholesterol reduced and higher HDL cholesterol. Same results as the 3.5 days fast. 

Drs Michael & Clare Mosley

Michaels wife Clare (a GP) was also delighted with his results (56m)! But more trials are needed to see whether Intermittent Energy Restriction is safe and effective. With diabetes and obesity timebomb set to explode we need as a nation a means to reverse the effects. Fasting could be the means.


Michael Mosley says 'I decided I couldn't manage ADF, it was just too impractical. Instead, I did an easier version, the so-called 5:2 diet [suggested by Mark Mattson]. As the name implies you eat normally 5 days a week, then two days a week you eat 500 calories if you are a woman, or 600 calories, if you are a man. There are no firm rules because so far there have been few proper human trials. I found that I could get through my fast days best if I had a light breakfast (scrambled eggs, thin slice of ham, lots of black tea, adding up to about 300 calories), lots of water and herbal tea during the day, then a light dinner (grilled fish with lots of vegetables) at night.  On my feed days, I ate what I normally do and felt no need to gorge. 

I stuck to this diet for 5 weeks, during which time I lost nearly a stone and my blood markers, like IGF-1, glucose, and cholesterol, improved. If I can sustain that, it will greatly reduce my risk of contracting age-related diseases like cancer and diabetes. 

Current medical opinion is that the benefits of fasting are unproven and until there are more human studies it's better to eat at least 2000 calories a day. If you really want to fast then you should do it in a proper clinic or under medical supervision, because there are many people, such as pregnant women or diabetics on medication, for whom it could be dangerous. I was closely monitored throughout and found the 5:2 surprisingly easy. I will almost certainly continue doing it, albeit less often. Fasting, like eating, is best done in moderation.' source: BBC

Info

1. http://en.wikipedia.org/wiki/Calorie_restriction (Accessed 12th August 2012)
2. http://www.theiflife.com/intermittent-fasting-101-how-to-start-part-i/  (Accessed 13th August 2012)
3. Letter to BBC from Paul McGlothin at CR Society - Mosley did not take account of his 'happiness biochemistry'!

Worm lifespan doubled - Cynthia Kenyon

reposted from: http://www.facebook.com/ajax/sharer/?s=99&appid=2309869772&p%5B0%5D=680125715&p%5B1%5D=239216616142237

Refs: Unlocking the Secrets of Longevity Genes; March 2006; Scientific American Magazine; by David A. Sinclair and Lenny Guarente; 8 page(s)

crabsallover highlights, key points, comments / links.

Eat less, live longer? Or Just eat less protein or methionine (become a Vegan) and live longer?

reposted from: New Scientist

• 03 June 2010 by Laura Cassiday
• Magazine issue 2762. Subscribe and save
• For similar stories, visit the Food and Drink Topic Guide

IN GREEK mythology, the tale of the Trojan prince Tithonus is a tragic one. His lover, the goddess Eos, asks Zeus to grant him eternal life, but forgets to specify eternal youth. Time passes, and while the goddess of dawn stays young and beautiful, Tithonus degenerates into bedridden senility. Eventually Eos shuts him in a chamber of her celestial palace, where his feeble voice can be heard begging for death.

Dreams of eternal youth feature in many cultures throughout history, but it was only in the 20th century that research into longevity really began. Much about ageing is still mysterious - we don't even know the underlying reasons why we journey into old age. There are many lines of enquiry into how to live longer, though, with one of the most intriguing being calorie restriction: in effect, going on a lifelong diet.

Calorie restriction dramatically extends not only the lifespan of laboratory animals, but also their "healthspan" - how long they live free of disease. On the assumption that it has the same effect in people, some individuals have already adopted a restricted diet. The latest evidence suggests that while calorie restriction is indeed beneficial for humans, when it comes to lifespan extension, it may not be the whole story.

The good news is that we might be able to delay ageing without cutting our food intake. "There's a definite possibility that if you balance the diet correctly, a longer lifespan can be achieved without full food restriction," says Matthew Piper, a researcher into ageing at University College London.

There is a definite possibility that if you balance the diet correctly, a longer lifespan can be achieved without full-on food restriction

Interest in calorie restriction began in 1935, when scientists made the surprising discovery that rats on a reduced-calorie diet lived longer, provided they were supplemented with sufficient vitamins and minerals. The idea sounds counter-intuitive; after all, a state of starvation is not usually conducive to health. But there seems to be a window of benefit. While lifespan is reduced if calories are cut too drastically, it can be extended by cutting them moderately (see graph).

Calorie restriction has since been shown to extend the lives of other organisms including yeast, nematode worms, fruit flies and mice. Mice, for example, live up to 50 per cent longer if their calorie intake is cut by 30 to 50 per cent. What's more, mammals are protected from a number of age-associated maladies such as cancer, heart disease, type 2 diabetes and Alzheimer's disease.

It is unclear why eating less should make animals live longer. While a restricted diet triggers numerous changes at the molecular and genetic levels, only some of these are common across all the species tested. 

However, there does seem to be a general principle that a dearth of nutrients causes organisms to divert resources away from growth and reproduction and towards basic survival functions. From an evolutionary perspective, these adaptations could help an organism survive famine.

Longevity pioneers

The million-dollar question is whether calorie restriction has a similar effect in people. Humans are longer-lived and clearly harder to study than flies or mice, but recently two sources of evidence have hinted that it does.

The first comes from a 20-year study of rhesus macaques, a species obviously closer to humans than worms and mice. When the macaques were about 10 years old, equivalent to young adulthood in humans, half the group were placed on a diet in which they received 30 per cent fewer calories than the others. While none has yet beaten the record for the longest-lived macaque in captivity (about 40 years), the latest results, reported last year, look promising. 

About 80 per cent of the calorie-restricted monkeys were still alive when the study was published, beating the control group's survival rate of 50 per cent. And the dieting animals were one-third less likely to have died from an age-related disease (Science, vol 325, p 201).

The second strand of evidence comes from studying people who are practising calorie restriction. The first enthusiasts banded together through an email forum in the early 1990s. The group has since evolved into the Calorie Restriction Society International, which now has over 3000 members who refer to themselves as "CRONies", short for Calorie Restriction with Optimal Nutrition.

Needless to say, this lifestyle is not for everyone. Some people report struggling with hunger pangs, and the society warns on its website that side effects can include feeling cold, poor wound-healing and temporary infertility. But many CRONies insist that hunger is not a big problem and that they actually feel happier and healthier on their frugal diet (see "A day in the life of a CRONie").

CRONies typically cut calories by 10 to 30 per cent of the recommended intake, and most hover around the lower limit of "normal" body mass index, at 18.5 kilograms per height-in-metres squared. 

To ensure they get all the nutrients they need without busting their calorie quota, their diet is mainly vegetable-based and must be carefully planned, often with the help of a computer program. "People think calorie restriction involves tiny portions, but these people are eating huge amounts of low-calorie, nutrient-dense food," says Luigi Fontana, a professor of medicine at Washington University in St Louis and head of the Division of Nutrition and Aging at the Italian National Institute of Health, who has studied CRONies for the past eight years.

As with the macaques, it is too soon to tell if calorie restriction extends lifespan. The oldest people in Fontana's studies are only in their 70s - the average life expectancy for Americans. But there is evidence suggesting that it extends healthspan. In 2007, Fontana showed that CRONies have optimal metabolic profiles, and low blood pressure and cholesterol levels (Experimental Gerontology, vol 42, p 709). "They have hearts that are 15 years younger than those of typical Americans their age," he says.

So far, so good. But Fontana has found a notable difference in the way people and animals respond to calorie restriction, and it is not great news. It involves a hormone made by the liver called insulin-like growth factor 1.

IGF-1 (wikipedia) has emerged as an important promoter of ageing. IGF-1 levels are lower than normal in worms, flies and mice on a restricted diet, and this is thought to be at least partly responsible for their longer lifespan. When it comes to people, however, CRONies have the same IGF-1 levels as the rest of us.

The explanation for this anomaly may lie in a new theory about how diet affects ageing. This says that it may not only be the drop in calories that is responsible for lifespan extension - in some species at least, perhaps it is also the accompanying drop in dietary protein.

One piece of evidence for this idea comes from studies in fruit flies and rodents. If these animals are fed special diets with less amino acids - the building blocks of proteins - they can eat as many calories as they want and still live longer. "These results clearly show that you don't need to restrict calories as a whole to get lifespan extension," says Piper, an author of the study on flies (Nature, vol 462, p 1061).

Further support for this idea comes from studying the molecular pathways inside cells that affect lifespan. A molecule called TOR (TOR in wikipedia) has been found to set off a chain of reactions that boost cell growth at the expense of longevity. Blocking TOR increases lifespan in all organisms studied to date, including yeast and mice (Aging Cell, vol 9, p 105). Crucially, the most potent activators of TOR are amino acids.

Where does the protein theory leave the CRONies? Fontana noticed that the people in his study group were eating high levels of protein, about 1.7 grams per kilogram of body weight per day. This is more than the US government-recommended intake of 0.8 g/kg/day, and higher than that in a typical American's diet, about 1.2 g/kg/day.

Accelerated ageing

So Fontana asked six CRONies to cut their protein intake to 0.95 g/kg/day while maintaining their usual calorie intake. After only three weeks on the low-protein diet, the CRONies showed a 25 per cent drop in their levels of IGF-1 (Aging Cell, vol 7, p 681). "Even if the CRONies are restricting their calories severely, if they're eating a high-protein diet, they're probably negating some of the most important beneficial effects," says Fontana.

If the new theory is right, then the whole concept of calorie restriction needs to be rethought. The very term would be misleading; Fontana and others have started referring to dietary restriction instead. As news of the study has spread, some CRONies have already reduced their protein intake.

The protein theory is bad news for people on low-carbohydrate weight-loss plans like the Atkins diet. "I'd be wary of diets that put a heavy emphasis on protein," says Piper. "It's hard to see how that could be healthy." Fontana goes one step further, saying that high-protein diets could risk accelerated ageing and cancer.

It's good news, however, for people already on low-protein diets, like vegans, who avoid eating meat, eggs and dairy products. In 2007, Fontana showed that vegans have lower levels of IGF-1 than meat-eaters (Rejuvenation Research, vol 10, p 225).

There may be another reason for vegans to celebrate. Studies on flies and rodents suggest that cutting intake of one particular amino acid, called methionine, lengthens life to a similar degree as calorie restriction. Proteins in meat and other animal products have high levels of methionine, so a vegan diet would score well by that measure, too (Medical Hypotheses, vol 72, p 125).

If calorie restriction would be hard for most people, calorie and protein restriction would be doubly so. Those determined to live to 130 may want to give it a shot, but for the rest of us, simply sticking to recommended dietary protein levels could have benefits for both lifespan and healthspan. "Protein restriction is much less difficult to maintain than [calorie] restriction and may be more powerful in reducing IGF-1 in humans," Fontana said in a recent review (Science, vol 328, p 321).

For those who don't fancy changing their diet, a more tempting prospect is a pill that replicates the effects without the hard work. Drug firms have taken a keen interest in trying to find such calorie-restriction mimetics, as they are sometimes called.

A decade ago the main focus was on signalling molecules called sirtuins (wikipedia) that reduce the expression of several ageing-related genes. Reports that resveratrol (wikipedia), a compound found in red wine, extended lifespan in some species by activating sirtuins boosted sales of red wine and resveratrol supplements. Resveratrol still has supporters, but inconsistent animal data have since dampened much of the enthusiasm.

The focus has lately switched to finding compounds that block TOR. One such agent is a drug called rapamycin (wikipedia), an immunosuppressant given to recipients of organ transplants. Last year rapamycin was found to extend the lifespan of mice, even in those started on the drug in later life, equivalent to 60-year-old humans (Nature, vol 460, p 392). However, because people don't live in a sanitised lab environment, rapamycin's strong immunosuppressive effects make it an unlikely candidate for a practical anti-ageing drug. Similar compounds that are less toxic would be more promising.

Another candidate is a drug called metformin (wikipedia), already used to treat type 2 diabetes. Metformin also blocks TOR, and lengthens lifespan in worms and mice (Cell Metabolism, vol 11, p 390). Does metformin slow ageing in people too? Studies published earlier this year suggest that diabetics taking metformin do get less cancer (Diabetes Care, vol 33, p 322). "The major risk factor for cancer, above all others, is ageing," says David Gems at University College London. He calls the studies a "smoking gun of a more generalised effect of metformin on ageing, rather than just strictly diabetes".

While metformin is less toxic than rapamycin, it, too, can have side effects, such as nausea and diarrhoea. So researchers may have a way to go before they find the perfect longevity pill.

And it would be premature to consider the case proven for the protein theory of lifespan extension. Even Fontana acknowledges there may be other nutrients that play a role, such as fatty acids or cholesterol. Others have speculated that it may be the ratio of calories to protein that is key.

In the meantime, the best bet for warding off ageing and disease could still be the time-honoured advice to eat your greens. Perhaps if vegetables had been the food of the gods, Tithonus could have enjoyed a few more quality years with Eos.

A day in the life of a CRONie

Paige Collins-Rideout, a 39-year-old medical transcriptionist in Blue Ridge, Georgia, does not look like she needs to diet, but that is exactly what she is doing. Collins-Rideout is a CRONie (which stands for Calorie Restriction with Optimal Nutrition), a member of a group who believe that eating a carefully controlled diet with 10 to 30 per cent fewer calories than recommended is key to a longer, healthier life.

For the past year-and-a-half, Collins-Rideout has been limiting her food intake to 1500 calories per day. At 1.7 metres (5 feet, 6 inches) tall, she weighs only 50 kilograms (110 pounds = 7st 12 pounds).

Vitamin-rich foods such as sweet potatoes, broccoli, spinach, eggs and whole grains are staples of Collins-Rideout's diet. Perhaps surprisingly, she says she is rarely hungry, although she admits to occasionally succumbing to unhealthy snacks like fried jalapeños. "Once in a great while I'll have something like that," she says. "Then I'm ready to go back to healthy eating."

There are downsides. Because it is hard to get the recommended levels of vitamins and minerals without supplements, which CRONies generally avoid, calorie restrictors often invest a great deal of time in planning and tracking their diet. To avoid becoming too underweight, Collins-Rideout has also cut back on her running - she used to jog 5 kilometres per day. She also says that social eating can be difficult.

But she says benefits of her diet include improved mood, sleep, mental clarity and memory. She has no desire to live to be 100, though. "My goal is to slow the ageing process so that when I get to retirement, I'll have the energy and vitality to actually live," she says. "I can't imagine going back to any other way of life."

Laura Cassiday is a science journalist based in Denver, Colorado