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Showing posts with label caloric restriction (CR). Show all posts
Showing posts with label caloric restriction (CR). Show all posts

Sunday, 2 September 2012

NPR.org » Subtracting Calories May Not Add Years To Life

NPR.org » Subtracting Calories May Not Add Years To Life

reposted from:
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Steven Austad: "There are some people following near-starvation diets in an effort to mimic the dramatic results seen in rodents, but not that many, because most people couldn't face that kind of dietary deprivation. "Don't feel so bad that you can't get yourself to this phenomenally lean, you might say emaciated, body state," says Austad, "because there's not any evidence that that's really going to help you live a lot longer anyway." But he says there's still no doubt that exercising and avoiding being overweight or obese will keep you healthier for your normal life span.

Mark Mattson - Ageing Research

reposted from: 
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Mark Mattson Background and Research Summary: http://www.grc.nia.nih.gov/branches/irp/mmattson.htm and http://www.grc.nia.nih.gov/branches/lns/mcnu.htm
New Scientist Article 2008: http://www.grc.nia.nih.gov/branches/lns/BestinSmallDoses.pdf
Hormesis Project: http://www.grc.nia.nih.gov/branches/lns/linka.htm



Saturday, 1 September 2012

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 highlightskey pointscomments / 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.

Saturday, 25 August 2012

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:
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"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.

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:
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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.

Wednesday, 22 August 2012

Mark P. Mattson talks about Intermittent Energy Fasting

reposted from: http://mpegmedia.abc.net.au/rn/podcast/2012/05/hrt_20120507_1740.mp3 via https://twitter.com/DrMichaelMosley# 17th August 2012

crabsallover highlightskey pointscomments / links.

Prof. Mark P. Mattson (ChNat. Inst. Ageing in Baltimore): CR in animals reduces cancer, kidney disease, diabetes - all animals live longer. Animals in wild are geered to feast or famine so the human 3 meals a day is abnormal from evolutionary standpoint. Intermittent energy restriction (IER) (eg 2 days a week have low calorie intake) imitates evolution. IER v daily CR (calorie restricted every day): IER has more powerful effects for nerve cells to resist stress and disease.

With IER before animals become symptomatic can protect brain: reduces Amyloid accumulation (gunk ceases up the brain) of Alzheimers disease and preserves dopamine producing neurons which reduces Parkinsons disease. On alternate Day Fasting, before symptoms become symtomatic, mice live 30% longer on IER.

IER reduced Oxidative stress (reduces rusting of brain ie reduced free radicals), reduced local inflammation (reduced cytokines eg tumour necrosis factor TNF - immune system less active so brain ages less).

Fasting increases production of protein neurotrophic factors (causes nerve cells to grow), increases stem cell Brain Derived Neurotrophic Factor (BDNF wiki) which increases production of nerve cells (neurogenesis). With increased exercise AND IEF, BDNF:-

  1. Strengthens neuron synapses - maintains cognitive function
  2. Increases antioxidant enzymes (counteract free radicals), suppresses free radicals and inflammation

Muscle Analogy

This increase in stress in your brain is analogous to exciting muscle cells which make them stronger and contract. Nerve cells when exited send signal to next neuron, become more active when they are hungry.  With mild stress - nerve cells become more active and this is evolutionary important.

Downside of IER 

Reduced wound healing, increased risk of infection for cave men ancestors.

Human Trials

In breast tumour patients (with Michelle Harvie, Wythenshawe Hospital, Uni Manchester reported by Daily Mail), Press Release, full article Int. Journal of Obesity. 100 subjects split into 3 groups. 1) control diet ate normally, 2) 15% reduction in calories (CER) 3) 5:2 day fast diet (IER) - had less insulin resistance than other groups.

IER and CER are equally effective for weight loss, comparable reductions in: leptin, C-reactive protein, total and LDL cholesterol, triglycerides, blood pressure, increased IGFBP-1 and IGFBP-2, negligible changes in total and free IGF-1.

on IER:-
  1. sugar reaching breast cells decreased 
    1. breast cells divide less frequently, reducing chances of cancer
  2. had fewer cancer-causing hormones in their blood six months later 
    1. Leptin fell by 40 per cent 
    2. Insulin fell by 25 per cent
    3. C-Reactive Protein fell by 15 per cent

Wednesday, 15 August 2012

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

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

Sunday, 20 November 2011

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)

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Saturday, 22 January 2011

Charlie Rose - Calorie Restriction

reposted from:
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Part 2


Part 3

- monkeys on CR (30% calorie reduction) have reduced type 2 diabetes, reduced colon cancer, body fat reduced by 70%, 55 genes involved in inflamation have lowered expression

Part 4

- humans on CR have reduced heart disease
- nematode worms live 2 weeks
- resveratrol effects activity of sirtuins (anti-ageing genes)

Part 5

- polyphenols

Saturday, 20 November 2010

Study looks at 'anti-ageing' in mice

reposted from: http://www.nhs.uk/news/2010/11November/Pages/study-looks-at-anti-ageing-enzyme.aspx

This was a laboratory study on mice with age-related hearing loss

A pill that could add decades to the average lifespan moved a step closer yesterday,” reported the Daily Express. It said that scientists have found an anti-ageing enzyme that protects cells from decay.


This research looked at how a calorie-restricted diet and the action of a protein called Sirt3 affected the development of age-related hearing loss in mice. It found that mice that were capable of producing Sirt3 in response to having a calorie-restricted diet had slower development of age-related hearing loss than those unable to produce Sirt3.
This laboratory study gives us a new insight into how restricting calories may protect cells against some of the processes of ageing, through the role of Sirt3. However, it cannot tell us whether this process occurs or has the same effect in humans, nor does it give any indication of whether it is possible to develop an anti-ageing pill based on this knowledge.

Where did the story come from?

The study was carried out by researchers from the University of Wisconsin, University of Tokyo and University of Florida. It was funded by the US National Institutes of Health, National
Projects on Protein Structural and Functional Analyses from the Ministry of Education, Culture, Sports, Science, and Technologies of Japan, and the Marine Bio Foundation. The study was published in the peer-reviewed scientific journal Cell.
The story was covered by the Daily Express and Daily Mail, both of which overstated the implications of the current findings. While the results of this study may one day contribute to medical therapies, it is too early to announce that an anti-ageing pill is on the way, and the claim that it could “add decades” to life is speculative.

What kind of research was this?

This was a laboratory study on mice with age-related hearing loss. It is thought that a process called oxidative stress causes damage to the cochlear cells in the inner ear, which can lead to age-related hearing loss. Oxidative stress is a process in which substances called free radicals cause damage to cells. This is thought to contribute to ageing. Previous research in animals has suggested that calorific restriction (a reduction of food consumption by 25–60%) can protect cochlear cells from this damage, but it is not fully understood how. Here, the researchers used mice to explore how this protective mechanism might work.
The researchers looked at the role of a group of proteins called sirtuins, known to be involved in the regulation of cell specialisation in mammals. They specifically focussed on Sirt3. Pervious studies have found that levels of Sirt3 increased in response to calorific restriction, in processes that suggest it has a role in delaying the effect of oxidative stress on ageing.
Extreme calorific restriction has been associated with increased lifespan in animal studies, but few studies have been able to explore this relationship properly in humans. It is not known if equivalent extreme calorie reduction in humans would have a similar effect, and how beneficial such an effect would be. This study did not investigate the effects of calorific restriction on human health or lifespan.

What did the research involve?

The researchers fed mice a diet that contained only 75% of their usual calorific intake. Some of these mice were able to produce Sirt3, while others lacked the gene that enables Sirt3 to be made. The researchers then examined the development of age-related hearing loss in both sets of mice after 12 months of calorific restriction.
They then looked at oxidative damage to DNA in a variety of cell types from the normal and Sirt3-deficient mice. Further experiments were carried out in different cell types from both sets of mice to examine the biochemical processes by which Sirt3 might reduce levels of oxidative stress and the damage this may cause to cells.

What were the basic results?

The researchers found that calorific restriction slowed the progression of age-related hearing loss in mice, but only in the mice that were naturally able to produce Sirt3. Mice that were Sirt3-deficient had typical rates of hearing loss. Similarly, the protection against DNA damage caused by oxidative stress was detected in the mice with normal Sirt3 production on a calorie-restricted diet, but was not seen in the Sirt3-deficient mice on the same diet.
The researchers found that calorific restriction triggered Sirt3 to activate a biochemical process that decreased the levels of oxidative stress and gave some protection to inner-ear cells. In turn, this reduced the risk of age-related hearing loss in those mice. They said that Sirt3 appears to have an important role in helping calorific restriction protect against the effects of ageing processes.

How did the researchers interpret the results?

The researchers propose that the biochemical mechanism they observed “may be a major mechanism of ageing retardation” due to the effects of calorific restriction. They propose that artificial stimulation of Sirt3 activity using pharmaceutical therapies may have a similar protective effect against the damage caused to cells by ageing processes.

Conclusion

This interesting laboratory study gives us a new insight into how calorific restriction may protect cells against some processes of ageing through the role of Sirt3. However, it cannot reveal whether this process occurs or has the same effect in humans, nor does it give any indication of whether it is possible to develop an anti-ageing pill based on this knowledge. Much further research is needed before this would be possible.

Links to the headlines

Pill to arrest ageing on way. Daily Express, November 19 2010

Links to the science

Someya S, Yu W, Hallows WC, et al. Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction. Cell 2010

Sunday, 31 October 2010

The Future of Aging: Pathways to Human Life Extension, pub. August 2010

reposted from: Amazon.co.uk. 'Look Inside' for Contents, Index and sample pages. Price: £191

Chapter 1: Bridges to Life by Ray Kurzweil & Terry Grossman argues that we should adopt a bridge strategy to keeping healthy and extending healthy lifespan. Bridge 1 is things we can do right now including exercise, nutritional supplementation and caloric restriction CR ('...in rats optimal level of caloric restriction... is 2/3 of ad libitum feeding' & 'for humans eat 20% less calories than ad libetum'  eg 180 pound moderately active man uses 2700 calories ad libetum, a 20% CR diet is 2160 calories per day.)

Bridges 2 biotechnology and 3 Nanoscience will come later so we must use Bridge 1 strategies to have a chance of living long enough to benefit from later Bridges ('we are only 15 years from maturation of the second bridge'). This chapter reviews their 2009 book 'Transcend: 9 Steps to Living Well Forever'.



Friday, 29 October 2010

Caloric Restriction will only ever give 2-3 years extra life

reposted from: http://www.sens.org/node/106 | Full article pdf


The unfortunate influence of the weather on the rate of aging: why human caloric restriction or its emulation may only extend life expectancy by 2-3 years.

Author(s): 
de Grey ADNJ.
User Author(s): 
Citation: 
Gerontology 2005; 51(2):73-82.
Abstract: 
Much research interest, and recently even commercial interest, has been predicated on the assumption that reasonably closely-related species--humans and mice, for example--should, in principle, respond to ageing-retarding interventions with an increase in maximum lifespan roughly proportional to their control lifespan (that without the intervention). Here, it is argued that the best-studied life-extending manipulations of mice are examples of a category that is highly unlikely to follow this rule, and more likely to exhibit only a similar absolute increase in maximum lifespan from one species to the next, independent of the species' control lifespan. That category--reduction in dietary calories or in the organism's ability to metabolize or sense them--is widely recognized to extend lifespan as an evolutionary adaptation to transient starvation in the wild, a situation which alters the organism's optimal partitioning of resources between maintenance and reproduction. What has been generally overlooked is that the extent of the evolutionary pressure to maintain adaptability to a given duration of starvation varies with the frequency of that duration, something which is--certainly for terrestrial animals and less directly for others--determined principally by the weather. The pattern of starvation that the weather imposes is suggested here to be of a sort that will tend to cause all terrestrial animals, even those as far apart phylogenetically as nematodes and mice, to possess the ability to live a similar maximum absolute (rather than proportional) amount longer when food is short than when it is plentiful. This generalization is strikingly in line with available data, leading (given the increasing implausibility of further extending human mean but not maximum lifespan in the industrialized world) to the biomedically and commercially sobering conclusion that interventions which manipulate caloric intake or its sensing are unlikely ever to confer more than 2 or 3 years' increase in human mean or maximum lifespan at the most.
PubMed ID: 
15711074

Monday, 25 October 2010

Is Caloric Restriction an Answer to the Obesity Epidemic at Older Ages?

reposted from: http://longevity-science.org/Gavrilov-ILS-Bermuda.ppt (slide 43)


Professor John E. Morley is an authority in geriatric medicine. John E. Morley et al., Current Opinion in Clinical Nutrition and Metabolic Care (2010):

“Dietary restriction in rodents has not been shown to be effective when started in older rodents. Weight loss in humans over 60 years of age is associated with increased mortality, hip fracture and increased institutionalization. Calorie restriction in older persons should be considered experimental and potentially dangerous.

Exercise at present appears to be a preferable treatment for older persons.” 

Thursday, 14 October 2010

Why dietary restriction substantially increases longevity in animal models but won’t in humans

reposted from: sciencedirect via http://ageaction.ncl.ac.uk/AgeAction_book.pdf



 by John P. Phelan and Michael R. Rose
Abstract
Caloric restriction (CR) extends maximum longevity and slows aging in mice, rats, and numerous non-mammalian taxa. The apparent generality of the longevity-increasing effects of CR has prompted speculation that similar results could be obtained in humans. Longevity, however, is not a trait that exists in a vacuum; it evolves as part of a life history and the physiological mechanisms that determine longevity are undoubtedly complex. Longevity is intertwined with reproduction and there is a cost to reproduction. The impact of this cost on longevity can be age-independent or age-dependent. Given the complexity of the physiology underlying reproductive costs and other mechanisms affecting life history, it is difficult to construct a simple model for the relationship between the particulars of the physiology involved and patterns of mortality. Consequently, we develop a hypothesis-neutral model describing the relationship between diet and longevity. Applying this general model to the special case of human longevity and diet indicates that the benefits of caloric restriction in humans would be quantitatively small.

Processed carbohydrates may increase health risks more than saturated fat does

reposted from: Scientific American, May 2010 (download full article) - Original Source (subscription required)

Carbs against Cardio 
More data that refined carbohydrates, not fats, threaten the heart
BY MELINDA WENNER MOYER

Processed carbohydrates, which many Americans eat today in place of saturated fat, may increase the risk of obesity, diabetes and heart disease more than fat does.

In March 2010 the American Journal of Clinical Nutrition published a meta-analysis—combines data from several studies—compared the reported daily food intake of nearly 350,000 people against their risk of de-veloping cardiovascular disease over a period of five to 23 years. The analysis, overseen by Ronald M. Krauss, director of atherosclerosis research at the Children’s Hospital Oakland Research Institute, found no association between the amount of saturated fat consumed and the risk of heart disease.

Although saturated fat boosts blood levels of “bad” LDL cholesterol, it also increases “good” HDL cholesterol.

Saturated fats are not so bad; they indicate that carbohydrates could be worse.

A 1997 study Krauss co-authored in the Journal of the American Medical Association evaluated 65,000 women and found that the quintile of women who ate the most easily digestible and readily absorbed carbohydrates—that is, those with the highest glycemic index—were 47 percent more likely to acquire type 2 diabetes than those in the quintile with the lowest average glycemic-index score. (The amount of fat the women ate did not affect diabetes risk.) And a 2007 Dutch study of 15,000 women published in the Journal of the American College of Cardiology found that women who were overweight and in the quartile that consumed meals with the highest average glycemic load, a metric that incorporates portion size, were 79 percent more likely to develop coronary vascular disease than overweight women in the lowest quartile.

These trends may be explained in part by the yo-yo effects that high glycemic-index carbohydrates have on blood glucose, which can stimulate fat production and inflammation, increase overall caloric intake and lower insulin sensitivity, says David Ludwig, director of the obesity program at Children’s Hospital Boston.

Right now, Post explains, the agency’s main message to Americans is to limit overall calorie intake, irrespective of the source.

“We’re finding that messages to consumers need to be short and simple and to the point,” he says. 

Nobody is advocating that people start gorging themselves on saturated fats, tempting as that may sound. Some monounsaturated and polyunsaturated fats, such as those found in fish and olive oil, can protect against heart disease. What is more, some high-fiber carbohydrates are unquestionably good for the body. But saturated fats may ultimately be neutral compared with processed carbs and sugars such as those found in cereals, breads, pasta and cookies.

“If you reduce saturated fat and replace it with high glycemic-index carbohydrates, you may not only not get benefits—you might actually produce harm,” Ludwig argues. The next time you eat a piece of buttered toast, he says, consider that “butter is actually the more healthful component.”

Sunday, 10 October 2010

Is science on the brink of creating the elixir of life?

reposted from: Daily Mail

Is science on the brink of creating the elixir of life?

By MICHAEL HANLON Last updated at 5:00 AM on 9th October 2010

Once I had a very odd dinner with an elderly and distinguished scientist who told me how he planned to live for ever - or at least for a very long time indeed. We ate in his beautiful house by the sea in California. Our meal consisted of one bowl of rice each and a glass of water. With this extreme diet, my host said - limiting himself to 800-1,000 calories a day (the average male is recommended to consume 2,500) - he hoped to stave off death for many more decades.

Such a regime was based on the well-established theory that by reducing calorie intake, people can dramatically increase their lifespans. This had been shown, after numerous scientific investigations, to work in animals from fruit flies to mice. Professor Roy Walford, a biologist at UCLA, was 74 years of age when I met him. He had no doubt that extreme calorie restriction would work in people, too. However, despite his punishing diet, he was to die five years later from the auto-immune disorder Lou Gehrig’s disease. Seventy-nine years was a little better than the three score years and ten which have been approximated as the human lot since Biblical times - but his innings only matched the average lifespan for an educated, middle-class white California male of his generation. It is tempting, then, in the light of this story, to write off the theory that by eating the bare minimum we can slow the ageing process. But it seems Professor Walford was probably on to something, even if the fates conspired to ensure that he personally did not benefit from his diet thesis.

For there is a growing scientific consensus that ageing - against which humanity has been battling for millennia - might not be inevitable.


Of course, the quest for eternal youth has been led by charlatans, frauds and snake-oil salesmen through the ages. There is money to be made by promising the Holy Grail - as the questionable claims on the labels of countless anti-ageing beauty products will attest. For centuries, lotions and potions have been touted as elixirs of longevity. These have ranged from products containing monkey glands to injections of minced dog testicles. Unsurprisingly, all have failed. Still, the search continues.

We have been told that exercise, red wine, chocolate, Vitamin C and various cocktails of antioxidants are the answers. The latest elixir claim comes from scientists in Italy, who announced this week that mice given dietary supplements rich in three amino acids (similar to the concoctions favoured by human bodybuilders) lived on average 12 per cent longer than mice fed on ordinary food (see: ScienceLongLife). For humans, this would mean about an extra ten years of life. And yet the world still awaits its first 125-year-old. The record stands at 122 years - achieved by Frenchwoman Jeanne Calment, who died in 1997. But the truth is, charlatans apart, the ageing process may be more amenable to change than was thought.

For a start, life expectancy (the number of years a newborn is predicted to live) is increasing by five hours a day in Britain. This means a baby born in five years’ time should live a year longer than a baby born today. This is, for the most part, simply a result of better healthcare. For evidence we need only look at the first big jump in life expectancy, which took place in the 19th century when infant mortality rates dropped because of improved diets, better medicine and proper sanitation. We haven’t conquered age, it’s just that more and more of us are living to our full potential. But we may now be nearing a surprising breakthrough.

According to a new book, The Youth Pill, by health journalist David Stipp (Amazon.co.uk) with a selection of reviews on his book at DavidStipp.com, in a few decades a number of pills may be available, which will help delay the onset of most serious illnesses by up to ten years. This would give us at least five extra years of healthy old age and allow the 122-year barrier to be breached.

Until recently, those scientists working on increasing the longevity of fruit flies or mice have shied away from making claims that humans could benefit from their work on genetics. But now, as Stipp points out, this attitude seems to be changing; more and more experts now say that human lifespan can be increased - and what’s more, they agree that it would be a good idea.

How we grew old, and why, was a mystery until recently. It was commonly supposed that our bodies simply wore out, like machines. But this wasn’t a good analogy. Unlike most machines, our bodies are equipped with efficient repair systems that keep our cells healthy for decades. In fact, we do not really start to ‘age’ at all until we are into our 20s. So, discovering why these mechanisms stop working as we enter middle and old-age is the key to understanding the ageing process. Ageing is, after all, not entirely inevitable. Several organisms appear to hardly age at all and live for centuries.

Humans are among the longest-lived of all species, but our longevity is exceeded by some giant tortoises which can live for nearly 200 years. Bowhead whales have recently been found, alive and well, with antique harpoons embedded in their skulls which can be dated back to the 1790s. Some of these animals may be more than 300 years old. There is a pattern in all this. Big creatures tend to live longer than small ones. Anything that can fly or swim tends to live longer than animals stuck on the ground. Understanding these differences gives us our first clue as to how ageing works - and to what might be done to delay it.

The evolutionary theory of ageing states that animals age at a rate commensurate to their likely survival time in the wild. Mice age quickly because - being small and feeble - they are likely to be eaten, starve or perish due to cold before too long. Evolution has given the mouse a body that literally lives fast and dies young. It’s full of sex hormones turbocharging its chances of reproducing before it is eaten by predators. It makes little sense for a mouse to be equipped with, say, anti-cancer mechanisms, if the chances are that it will be an owl or cat’s dinner within a year or two.

On the other hand, elephants age slowly because, being big, they are hard to kill. It takes a long time for them to die of starvation and they cope well when times get tough. So elephant bodies have evolved complex DNA repair systems which can keep them going for half a century or more.

Birds also live a long time because, although small, they can fly and thus avoid predators. Bats live longer than mice for the same reason, and porcupines and tortoises are long-lived simply because they make a difficult meal. In each case, their bodies age slowly to make the most of their potential life spans. Still, knowing why we age tells us little about how we age - and even less about what we might be able to do about it. There is growing evidence, however, that the very hormones that enable us to reproduce - those which produce eggs and sperm - may in themselves contribute to the ageing process. ‘Death,’ said one biologist, ‘is the price we pay for sex.’

Advances in DNA analysis - reading the entire genetic codes of organisms - have opened up exciting new areas in ageing research, allowing scientists to pinpoint individual genes which may be be responsible for the breakdown in our bodies over time. Yet the reality is that many of the resulting ‘breakthroughs’ have proved to be dead ends. For decades, ‘free radicals’ (waste chemicals produced by our bodies as by-products of respiration, digestion and the action of muscles) have been suggested as possible drivers of the ageing process.

Big creatures tend to live longer than small ones. Anything that can fly or swim tends to live longer than animals on the ground.

Some scientists have claimed that we should take large quantities of free-radical neutralisers called antioxidants (which include Vitamin C and are best found in fruit and vegetables). Yet Vitamin C, it turns out, may actually increase free-radical damage and very large doses can interfere with the body’s natural repair mechanisms.

It is such contradictions that have led researchers to focus, instead, on calorific restriction. Mice placed on near-starvation diets have seen their life expectancies increase 20-35 per cent. If such results were achievable in humans, the average Briton’s life expectancy would rise to almost 100 - with the potential to carry on to 150. This is precisely what Professor Roy Walford was trying to achieve with his grimly tedious rice and water diet in California. And the truth is that research into whether calorie restriction will greatly extend our lifespans would take decades to reach firm conclusions - simply because we are so much larger than mice.

Even so, research on rodents has uncovered how extreme calorie restriction appears to switch on a genetic mechanism called a stress response. This has evolved to allow animals to survive tough conditions (such as a very hard winter when little food is available). It seems the bodies of mice - and possibly those of humans, too - react to starvation by boosting their repair mechanisms, triggering anti-inflammatory responses which slow the damage done to vital organs as they age.

The problem for humans is that near-starvation is unlikely to catch on. What people are much more likely to turn to are drugs which mimic the effects of extreme calorie restriction, without having to live on lettuce. And such drugs may soon be available. One could be based on the chemical resveratrol which is a plant compound found in red wine. In 2006, Harvard scientist David Sinclair found that this could activate a stress-response gene called Sir2 in mice which extended their lives.

Vast fortunes are being spent by the big drug firms on anti-ageing drugs

The happy fact that the elixir of youth is found in wine was suggested as the possible reason why the French, who eat a lot of supposedly unhealthy meat and cheese, smoke too much and drink a lot of alcohol, have one of the world’s highest life expectancies.

Then, last year, three teams of researchers in the U.S. reported that another chemical which mimics the effects of starvation, called rapamycin, makes mice live longer by suppressing the onset of cancer. The chemical was isolated from a fungus found on Easter Island in the Pacific. Unsurprisingly, the big drug firms are trying to exploit these discoveries. Vast fortunes are being spent on anti-ageing drugs which mimic calorie restriction. The problem, sceptics point out, is that the ageing mechanism in rodents may be quite different to the one in humans.

Therefore, resveratrol and similar chemicals may not prove to be the answer (the same may be true of the Mr Universe protein supplements trumpeted this week). But the likelihood is that, in a few years, pills will be developed that will be able chemically to copy the effects of a near-starvation diet and that may well increase lifespan in humans.

If this happens, what would a world of 130-year-olds be like? Of course, there is a big difference between being a healthy 130-year-old and someone who has spent the last 40 years of their life suffering from dementia. So what about the anti-ageing pioneer Roy Walford? Ironically, his death was caused by a rare disease that is exacerbated, not ameliorated, by a low-calorie diet. But if he was right, then by helping publicise what was once an obscure field of scientific research, his last, hungry years by the Pacific may not have been in vain.