New study on CR in humans

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Re: New study on CR in humans

Postby JeffN » Sat May 11, 2013 6:06 am

A very long and detailed post on the opposing outcomes of the nonhuman primate CR studies at the Wisconsin National Primate Research Center (WNPRC) and at the National Institute on Aging (NIA). It is also one of the most comprehensive reviews of the available data on CR.

http://www.sens.org/research/research-b ... d-mimetics

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Re: New study on CR in humans

Postby JeffN » Wed Apr 02, 2014 7:51 am

A new paper in Nature Communication by the University of Wisconsin CR researchers that reinforces their previous finding that CR does indeed extend lifespan in rhesus monkeys.

Monkeys fed ad lib were 2.8 times as likely to die of age-related causes at any point in time, and 1.8 times as likely to die of all causes at any point in time relative to the CR-fed animals.

*Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys*
Nature Communications 5, Article number: 3557doi:10.1038/ncomms4557

http://www.nature.com/ncomms/2014/14040 ... s4557.html

Abstract

Caloric restriction (CR) without malnutrition increases longevity and delays the onset of age-associated disorders in short-lived species, from unicellular organisms to laboratory mice and rats. The value of CR as a tool to understand human ageing relies on translatability of CR's effects in primates. Here we show that CR significantly improves age-related and all-cause survival in monkeys on a long-term ~30% restricted diet since young adulthood. These data contrast with observations in the 2012 NIA intramural study report, where a difference in survival was not detected between control-fed and CR monkeys. A comparison of body weight of control animals from both studies with each other, and against data collected in a multi-centred relational database of primate ageing, suggests that the NIA control monkeys were effectively undergoing CR. Our data indicate that the
benefits of CR on ageing are conserved in primates.


The authors acknowledge their results contrast with the recently-reported results of the NIA study of CR in rhesus monkeys, and attributes the discrepancy to the NIA control monkeys being slightly calorie restricted, making them statistically indistinguishable from the CR group.

http://www.nytimes.com/2014/04/02/scien ... evity.html

"The upshot is that even their control animals had a diet that was restricted in calories, at least to a moderate extent, Rozalyn M. Anderson and colleagues from Dr. Weindruch's team say in the new report. So no wonder the Baltimore test monkeys fared little better than the controls -- both were benefiting from caloric restriction, Dr. Anderson says. Moreover, the Baltimore study indicates that the minor restriction of calories may be just as effective as significant restriction. If so, "this would be an extremely important discovery," Dr. Anderson writes."

If this finding is correct and applies to humans the implications are important and are inline with the perspective I have been expressing here in this forum on CR-ON, which is moderate restriction is as good as it gets. No need to restrict more. This is not about some extreme form of calorie restriction, nor putting oneself at risk, nor having to go hungry all the time.

viewtopic.php?f=22&t=37450

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Re: New study on CR in humans

Postby JeffN » Sat Apr 19, 2014 6:20 am

Calorie Restriction in Rhesus Monkeys and Humans: A short review of the effects on health and lifespan.

Wednesday, April 16, 2014
Matthew Lake

http://matts-cr.blogspot.com/2014/04/ca ... s.html?m=1

Since the 1980s researchers have been conducting an experiment on rhesus monkeys by restricting their calories to see if CR is beneficial in improving their health and ultimately slowing down ageing, as it does in other species such as yeast, worms, flies, spiders, rats, mice, dogs, cows, among others the diet has been tested on. Rhesus monkeys live around 27 years on average, and are thought to be the most similar physiologically to humans — so it's believed the results would be more translatable to humans. Pending the final results, I'll go into what the current findings are, what they could mean, and whether or not the work is likely to be translatable to people.
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Re: New study on CR in humans

Postby JeffN » Tue Jan 17, 2017 2:46 pm

Caloric restriction improves health and survival of rhesus monkeys
Nature Communications 8, Article number: 14063 (2017)

Published online:
17 January 2017
http://www.nature.com/articles/ncomms14063

Abstract

Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late 1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity. We describe differences in study design that could contribute to differences in outcomes, and we report species specificity in the impact of CR in terms of optimal onset and diet. Taken together these data confirm that health benefits of CR are conserved in monkeys and suggest that CR mechanisms are likely translatable to human health.




Calorie restriction lets monkeys live long and prosper
https://medicalxpress.com/news/2017-01- ... osper.html
January 17, 2017

Settling a persistent scientific controversy, a long-awaited report shows that restricting calories does indeed help rhesus monkeys live longer, healthier lives.

A remarkable collaboration between two competing research teams—one from the University of Wisconsin-Madison and one from the National Institute on Aging—is the first time the groups worked together to resolve one of the most controversial stories in aging research.

The findings by the collaboration—including Senior Scientist Ricki Colman of the Wisconsin National Primate Research Center and UW-Madison Associate Professor of Medicine Rozalyn Anderson; and NIA Staff Scientist and Nonhuman Primate Core Facility Head Julie Mattison and Senior Investigator and Chief of the Translational Gerontology Branch Rafael de Cabo—were published today (Jan. 17, 2017) in the journal Nature Communications.

In 2009, the UW-Madison study team reported significant benefits in survival and reductions in cancer, cardiovascular disease, and insulin resistance for monkeys that ate less than their peers. In 2012, however, the NIA study team reported no significant improvement in survival, but did find a trend toward improved health.

"These conflicting outcomes had cast a shadow of doubt on the translatability of the caloric-restriction paradigm as a means to understand aging and what creates age-related disease vulnerability," says Anderson, one of the report's corresponding authors. Working together, the competing laboratories analyzed data gathered over many years and including data from almost 200 monkeys from both studies. Now, scientists think they know why the studies showed different results.

First, the animals in the two studies had their diets restricted at different ages. Comparative analysis reveals that eating less is beneficial in adult and older primates but is not beneficial for younger animals. This is a major departure from prior studies in rodents, where starting at an earlier age is better in achieving the benefits of a low-calorie diet.

Second, in the old-onset group of monkeys at NIA, the control monkeys ate less than the Wisconsin control group. This lower food intake was associated with improved survival compared to the Wisconsin controls. The previously reported lack of difference in survival between control and restricted groups for older-onset monkeys within NIA emerges as beneficial differences when compared to the UW-Madison data. In this way, it seems that small differences in food intake in primates could meaningfully affect aging and health.

Third, diet composition was substantially different between studies. The NIA monkeys ate naturally sourced foods and the UW-Madison monkeys, part of the colony at the Wisconsin National Primate Research Center, ate processed food with higher sugar content. The UW-Madison control animals were fatter than the control monkeys at NIA, indicating that at nonrestricted levels of food intake, what is eaten can make a big difference for fat mass and body composition.

Finally, the team identified key sex differences in the relationship between diet, adiposity (fat), and insulin sensitivity, where females seem to be less vulnerable to adverse effects of adiposity than males. This new insight appears to be particularly important in primates and likely is translatable to humans.
The upshot of the report is that caloric restriction does indeed seem to be a means to affect aging. However, for primates, age, diet and sex must all be factored in to realize the full benefits of lower caloric intake.




DAILY NEWS 17 January 2017
Calorie restriction diet extends life of monkeys by years
Eat less, live more?

By Clare Wilson

Put down the cake. Going on a permanent diet could make you live longer, if findings from monkeys hold true for people.

A long-running trial in macaques has found that calorie restriction makes them live about three years longer than normal, which would translate to about nine years in people.

Such a strict diet might not be for everyone, but understanding the mechanisms behind any benefits of calorie restriction may one day lead to anti-ageing medicines, says Julie Mattison at the National Institute on Aging (NIA) in Baltimore, Maryland. “The goal is to improve human health,” she says.

Many studies have shown that calorie restriction extends lifespan for lab organisms, from yeast through to worms, flies and mice. This has prompted a few thousand people to choose to restrict their calories to between 1500 to 1800 kcal a day (women and men are usually advised to consume 2000 and 2500 kcal, respectively). Their hope is it will give them longer and healthier lives, and there’s some evidence that such people have better blood cholesterol and glucose levels.

Age record breakers
But it’s unclear if the approach can really lengthen the lives of long-lived animals like us. Two trials of calorie restriction in macaques, which live around 26 years in captivity, have until now produced conflicting results.
The trials were set up in the late 1980s, and not all the monkeys have died yet. But an interim report from one group, based at the University of Wisconsin, previously found that the monkeys on a restricted diet were indeed living longer than the control group. However, the second study, run by the NIA, found there was no difference in the survival rates of their animals, which cast doubt on the entire premise.

Now the teams have compared their most recent results and their analysis backs the earlier trial that had positive findings. The NIA study, on the other hand, had several problems, including issues with the control group eating fewer calories than expected, and some of the animals beginning their restricted diet as juveniles – which reduces lifespan.
Even so, in the NIA trial, four of the monkeys that began the diet as adults lived to be over 40, breaking all known records for macaques – an observation which may cheer those who practise calorie restriction. However, picking out single results like this from a larger study isn’t good evidence, says Mattison.

Side effects
In the Wisconsin trial, animals did live significantly longer than controls – calorie-restricted males lived about two years longer, while calorie-restricted females lived about six years longer. There were also lower rates of heart disease and cancer in these monkeys. These are the major causes of death in people, lending support to the idea that the results apply to humans, says Luigi Fontana of the University of Brescia in Italy.

However, Brian Delaney, who is president of the Calorie Restriction Society, an organisation that supports the practice in people, says some who follow this diet are disappointed by the relatively modest benefits in monkeys compared with mice, which have lived up to 50 per cent longer than normal.

“Is it worth it?” asks Delaney. “My choice is to do it. But I’m so used to the diet that it really isn’t very difficult for me anymore.”

Delaney has been practising calorie restriction for 24 years. Until someone is used to it, the diet involves planning every meal with precision, and side effects can include feeling cold and reduced libido.
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Re: New study on CR in humans

Postby geo » Wed Jan 18, 2017 12:05 am

Until someone is used to it, the diet involves planning every meal with precision...


You mean like a big plateful of rice and beans with some veggies and an apple for desert and a big glass of water to wash it down?
That kind of planning and precision?

...and side effects can include feeling cold...


You mean like being in a Michigan winter when its 10 F and 40 MPH winds? Dress in layers :-)

...and reduced libido.


Uhmmmm, I don't think so...and neither does my wife...yes, I speak from experience :nod:

Why not just do the MWL, the REAL CRON (TM)...all the ON without the CR, no side effects (except the increased libido) or the need for planning or precision :lol:
geo

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Re: New study on CR in humans

Postby Doug_ » Sat Feb 25, 2017 7:19 am

Thanks Jeff for posting the recent study. And the reminder of why the basic guidelines remain sufficient and unchanged. This will be interesting to follow as the experiments and reports continue.
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Re: New study on CR in humans

Postby JeffN » Tue Apr 11, 2017 2:08 pm

Simpson, S.J., et al., Dietary protein, aging and nutritional geometry. Ageing Res. Rev. (2017),
http://dx.doi.org/10.1016/j.arr.2017.03.001

https://www.ncbi.nlm.nih.gov/pubmed/28274839

Highlights

•Aging is delayed by restriction of calories, protein and specific amino acids.
•Nutritional geometry provides new perspectives on the relationship between nutrition and aging.
•Low protein, high carbohydrate diets generate longest lifespan in ad libitum fed animals.

Abstract
Nearly a century of research has shown that nutritional interventions can delay aging and age- related diseases in many animal models and possibly humans. The most robust and widely studied intervention is caloric restriction, while protein restriction and restriction of various amino acids (methionine, tryptophan) have also been shown to delay aging. However, there is still debate over whether the major impact on aging is secondary to caloric intake, protein intake or specific amino acids. Nutritional geometry provides new perspectives on the relationship between nutrition and aging by focusing on calories, macronutrients and their interactions across a landscape of diets, and taking into account compensatory feeding in ad libitum-fed experiments. Nutritional geometry is a state-space modelling approach that explores how animals respond to and balance changes in nutrient availability. Such studies in insects and mice have shown that low protein, high carbohydrate diets are associated with longest lifespan in ad libitum fed animals suggesting that the interaction between macronutrients may be as important as their total intake.

Conclusions
A large number of nutritional interventions have been reported to increase lifespan in laboratory models. These interventions include caloric restriction, protein restriction, low protein high carbohydrate diets, and restriction of various essential amino acids. The results confirm that aging is malleable and provide a platform for dietary guidelines and drug development in order to harness the ‘longevity dividend’. However, diet is complex with interactions between macronutrients, compensatory feeding responses and uncertainty about reference diets influencing interpretation of outcomes. Nutritional geometry provides an approach to unravelling some of the complexities that link diet, aging and health.

From the article

"Using this Geometric Framework approach, it is possible to pin- point the optimum diet (‘sweet point’) for any outcome including lifespan or reproduction that takes into account the macronutri- ents, their interactions and energy intake (Le Couteur et al., 2016a; Simpson and Raubenheimer, 2012). There have been at least seven of these studies evaluating lifespan (and in some cases reproduc- tion) in insects and one in mice (Le Couteur et al., 2016a; Solon-Biet et al., 2014). The results are consistent across the studies. Longest lifespans are generated by diets that are low in protein and high in carbohydrates (LPHC) where the optimum ratio of protein to carbo- hydrates is about 1:10, with the protein content of the diet as low as 10% or less.

...

Interestingly, the longest living population in the world, the Japanese citizens of the island of Okinawa, have traditionally eaten a diet where the protein intake is 9%, and the macronutrient ratio of protein to carbohydrates is 9:85, almost identical to the ratio found to optimize lifespan in the Geometric Framework animal studies (Le Couteur et al., 2016b).
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Re: New study on CR in humans

Postby JeffN » Sun May 28, 2017 12:44 pm

Change in the Rate of Biological Aging in Response to Caloric Restriction: CALERIE Biobank Analysis
J Gerontol A Biol Sci Med Sci glx096.
DOI: https://doi.org/10.1093/gerona/glx096
Published: 22 May 2017

Abstract
Biological aging measures have been proposed as proxies for extension of healthy lifespan in trials of geroprotective therapies that aim to slow aging. Several methods to measure biological aging show promise; but it is not known if these methods are sensitive to changes caused by geroprotective therapy. We conducted analysis of two proposed methods to quantify biological aging using data from a recently concluded trial of an established geroprotector, caloric restriction. We obtained data from the National Institute on Aging CALERIE randomized trial through its public-access biobank (https://calerie.duke.edu/). The CALERIE trial randomized N=220 non-obese adults to 25% caloric restriction (n=145; 11.7% caloric restriction was achieved, on average) or to maintain current diet (n=75) for two years. We analyzed biomarker data collected at baseline, 12-, and 24-month follow-up assessments. We applied published biomarker algorithms to these data to calculate two biological age measures, Klemera-Doubal Method Biological Age and homeostatic dysregulation. Intent-to-treat analysis using mixed-effects growth models of within-person change over time tested if caloric restriction slowed increase in measures of biological aging across follow-up. Analyses of both measures indicated caloric restriction slowed biological aging. Weight loss did not account for the observed effects. Results suggest future directions for testing of geroprotective therapies in humans.




Caloric Restriction May Slow Biological Aging
May 25, 2017

http://www.empr.com/news/aging-caloric- ... le/664118/

(HealthDay News) — Limiting calorie intake may slow aging, according to a study published online May 22 in the Journals of Gerontology, Series A: Biological Sciences and Medical Sciences.

The researchers looked at 145 people who achieved a 11.7 percent reduction in calorie intake over two years and a control group of 75 people who did not restrict calories. At the start of the study, the average biological age of participants in both groups was 37, and their chronological age was 38.

Using two biological age measures, Klemera-Doubal Method Biological Age and homeostatic dysregulation, the researchers report that caloric restriction appeared to slow biological aging. They further noted that weight loss did not account for the observed effects.

"Ours is the first study to test if caloric restriction can slow measured biological aging in humans in a randomized setting," study author Daniel Belsky, Ph.D., an assistant professor of medicine at the Duke University School of Medicine in Durham, N.C., said in a Duke news release. "Our findings suggest a template for developing and evaluating therapies designed to mimic the effects of caloric restriction to ultimately prevent chronic diseases."
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Re: New study on CR in humans

Postby JeffN » Thu Jun 01, 2017 11:09 am

A fairly good MMA article on CR

The secret to a long and healthy life? Eat less
Permanently cutting the daily calories you consume may turn out to have a profound effect on your future life, according to some tantalising scientific studies.
BBC
By Alex Riley
1 June 2017

http://www.bbc.com/future/story/2017060 ... e-eat-less

"But the latest results suggested that significant health benefits can be garnered in an already healthy body – a person who isn’t underweight or obese. That is, someone whose BMI lies between 18.5 and 25."
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Re: New study on CR in humans

Postby JeffN » Mon Apr 23, 2018 9:02 am

Why context and perspective matter and why breaking news and single studies do not.

https://www.crsociety.org/topic/11699-w ... e/?p=28679

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