Study: Living longer? Eat less!

Geschatte leestijd: 5 minutenLiving Longer by Eating Fewer Calories? Nice, but Can You Fake It?

Table of Contents

• Fewer Calories, Longer Life
• Fewer Calories, Less Aging Damage to DNA
• Yay, Eating Less!
• Faking Calorie Restriction with Ketones

Fewer Calories, Longer Life

What a crappy article. Winter is coming, time to bulk up, and then I start talking about calorie restriction, limiting the amount of calories you eat. With that, you won’t have to show up in Las Vegas this weekend, where the Mr. Olympia participants eat on average between 6000 and 10,000 calories a day.

Don’t kill the messenger, as they say.

About 80 years ago, initial research showed that calorie restriction can significantly increase the lifespan of rats [1]. More recent work has replicated these results in various types of mice and monkeys [2,3]. However, it is not clear why eating fewer calories (sometimes less than a normal nutritional requirement) extends lifespan.

However, since last year, several studies have emerged offering various explanations for the life-extending effect of calorie restriction.

Let’s start with the most recent research, the findings of which were published this month in Nature Communications [4].

Fewer Calories, Less Aging Damage to DNA

Why do humans live longer than monkeys and monkeys longer than mice? Researchers at Temple University explain this by differences in DNA methylation. That sounds complicated, and it actually is, sorry. We’ve discussed this before in an article about the hereditary damage a father can cause to his offspring by drinking too many energy drinks. We’re talking about epigenetics, reversible heritable changes in genes without changes to the DNA sequence itself. DNA methylation is one form of this, involving the addition of methyl groups to DNA, altering its function.

In essence, as age increases, larger epigenetic changes occur, epigenetic drift, as the researchers call it. In their research, they showed that these changes occur much faster in mice than in monkeys and much faster in monkeys than in humans. According to them, this explains why mice live an average of only 2 to 3 years, monkeys about 25 years, and humans 70 to 80 years. They reached this conclusion by comparing these DNA changes due to aging among these three life forms.

In other words, the greater the amount of epigenetic change — and the more quickly it occurred — the shorter the species’ lifespan. Our next question was whether epigenetic drift could be altered to increase lifespan.

Dr. Issa, Temple University

Next, the researchers experimented by giving young mice 40% fewer calories and older mice 30% fewer. Both led to a significant reduction in epigenetic changes. To such an extent that these adjustments in older mice were comparable to those in young mice.

The impacts of calorie restriction on lifespan have been known for decades, but thanks to modern quantitative techniques, we are able to show for the first time a striking slowing down of epigenetic drift as lifespan increases.

Previous studies have shown a correlation between higher epigenetic changes and age-related diseases such as cancer. Temple University’s research shows that targeting these changes could be a way to reduce the risk of diseases.

The researchers hope to find more factors that can explain the differences in the speed of epigenetic drift in different individuals.

Yay, Eating Less!

I did say it was a crappy article. No one wants to hear the message that you have to eat less to live longer, except perhaps the less fortunate in this world.

It is important to realize, however, that when researchers talk about calorie restriction to extend lifespan, they are mainly referring to calories and not nutritional value. In these studies, as many “empty” calories as possible are cut out. Food that provides a lot of calories but few nutrients. Simply starving yourself is not a good method for living longer, of course. Eating less junk, that’s the key.

To make this article a bit more cheerful, however, I can also mention a more pleasant-sounding alternative to eating less (junk).

Faking Calorie Restriction with Ketones

Epigenetic changes are not the only explanation scientists offer for the effect of reducing calories on lifespan.

A theory that has been known for a while has to do with digestive processes such as the action of insulin (and IGF-1), oxidative stress, and the formation of free radicals [5,6]. Earlier this year, the results of researchers who published a review in IUBMB Life appeared [7]. Like the later research on epigenetic changes, these researchers also wondered what explained this effect of calorie restriction in so many different life forms from yeast to fruit flies and the aforementioned mice, monkeys, and humans [1,2,3,8,9]. However, this team of researchers looked at the similarity in metabolic process when there are few calories coming in; ketosis.

In short: When the body does not have enough glucose (sugars) to burn, it switches to burning fats. This releases molecules called ketone bodies. Fats cannot supply energy to the brain, and the ketone bodies thus provide an alternative route to supply energy to the brain as carriers of fatty acids.

According to the team of researchers, these ketone bodies could provide an explanation for why calorie restriction extends lifespan. However, there are also synthetic (esters of) ketone bodies that have been tested in research for combating Alzheimer’s, among other things [10]. The fact that such ketone bodies, which are not produced by the body itself, could mimic its effect was shown in a study with roundworms. When such a ketone body, d-βHB, was administered to the roundworms, it extended their lifespan [11]. Other studies with mice and rats showed that d-βHB reduces blood sugar and insulin, one of the possible explanations for its lifespan-extending effect.

So now we just have to wait until this source of eternal youth is sold for $49.95 on Tel Sell.

References

1. McCay, C. M., Crowell, M. F. & Maynard, L. A. The effect of retarded growth upon the length of life span and upon the ultimate body size. Nutrition 5, 63–79 (1935).
2. Swindell, W. R. Dietary restriction in rats and mice: a meta-analysis and review of the evidence for genotype-dependent effects on lifespan. Ageing Res. Rev. 11, 254–270 (2012).
3. Colman, R. J. et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325, 201–204 (2009).
4. Shinji Maegawa, Yue Lu, Tomomitsu Tahara, Justin T. Lee, Jozef Madzo, Shoudan Liang, Jaroslav Jelinek, Ricki J. Colman, Jean-Pierre J. Issa. Caloric restriction delays age-related methylation drift. Nature Communications, 2017; 8 (1) DOI: 10.1038/s41467-017-00607-3
5. Masoro, E. J. (2009) Caloric restriction-induced life extension of rats and mice: a critique of proposed mechanisms. Biochim. Biophys. Acta. 1790, 1040–1048.
6. Junfang Wu, Liu Yang, Shoufeng Li, Ping Huang, Yong Liu, Yulan Wang, Huiru Tang. Metabolomics Insights into the Modulatory Effects of Long-Term Low Calorie Intake in Mice. Journal of Proteome Research, 2016; 15 (7): 2299 DOI:
7. Veech, R. L., Bradshaw, P. C., Clarke, K., Curtis, W., Pawlosky, R. and King, M. T. (2017), Ketone bodies mimic the life span extending properties of caloric restriction. IUBMB Life, 69: 305–314. doi:10.1002/iub.1627
8. Lee, S. H. and Min, K. J. (2013) Caloric restriction and its mimetics. BMB Rep. 46, 181–187.
9. Klass, M. R. (1977) Aging in the nematode Caenorhabditis elegans: major biological and environmental factors influencing life span. Mech. Age. Dev. 6, 413–429.
10. Veech R.L. and King, M.T. (2017) Alzheimer’s disease: causes and treatment. In: Ketogenic Diet and Metabolic Therapy (Masino, S. A., ed.). pp. 241–253,Oxford University Press, Oxford
11. Edwards, C., Copes, N., and Bradshaw, P. C. (2015) D-ss-hydroxybutyrate: an anti-aging ketone body. Oncotarget 6, 3477–3478.
12. Kashiwaya, Y., Pawlosky, R., Markis, W., King, M. T., Bergman, C., et al. (2010) A ketone ester diet increases brain malonyl-CoA and Uncoupling proteins 4 and 5 while decreasing food intake in the normal Wistar Rat. J. Biol. Chem. 285, 25950–25956.
13. 78Srivastava, S., >Kashiwaya, Y., King, M. T., Baxa, U., Tam, J., et al. (2012) Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet. FASEB J. 26, 2351–2362