Calorie Restriction as the "Most Reasonable Anti-Aging Intervention"

The practice of calorie restriction slows aging in near all species and lineages tested to date. It produces significant health benefits in humans. Unfortunately the gain in life span scales down as species life span scales up. While calorie restriction extends maximum life span in mice and median life span in short-lived, small primates by 40% or more, it is not likely to have an effect size of more than five years when it comes to human life spans. That said, calorie restriction is by far the most robust and well tested of the few means available to adjust life span. Is it, however, as the authors of this paper would have it, the "most reasonable anti-aging intervention?"

Reliability is good, but size of effect is also important. Calorie restricted individuals still age and die on much the same schedule as the rest of us, just a fraction less rapidly. Good health practices can't add decades to life: three quarters of the healthiest people are dead by age 90, even given access to the best of medical technology over the course of the past half century. Calorie restriction, like exercise, is something that everyone should consider because it is essentially free, and has some benefit. But future life spans will be determined by new medical technology such as senolytic therapies, built on the SENS model of repairing the damage that causes aging, not by calorie restriction or recreation of some of its effects via pharmaceuticals.

Research on the biology of ageing has been conducted for centuries. Survival curves showing the surviving proportion of a population versus time are an intuitive means of illustrating the whole lifespan of a group of organisms and remain a key component of ageing research. Various anti-ageing interventions have been demonstrated to extend the lifespan of model organisms ranging from nematodes to fruit flies to rodents, with contradictory reports in rhesus monkeys. These interventions have mainly included calorie restriction (CR), genetic manipulations, and pharmaceutical administration.

However, whether these interventions extend the lifespan via universal or distinct patterns remains unclear. Traditionally, in ageing research, survival data from lifespan experiments are mainly analysed in the original study, and data are not collected and stored together. Meta-analyses are mainly limited to either sufficiently large subsets of survival data acquired under identical conditions or the application of methods accounting for varying additional factors. The published meta-analyses of survival data have mostly assessed CR. For example, reportedly, CR significantly extends lifespan, and the proportion of protein intake is more important for lifespan extension than the degree of CR. No study has demonstrated whether CR, genetic manipulation, or pharmaceutical administration is superior at extending lifespan and delaying ageing.

Here, we attempted to resolve this question by conducting a comprehensive and comparative meta-analysis of the effect patterns of these different interventions and their corresponding mechanisms via survival curves. We have focused our analyses on Caenorhabditis elegans and Drosophila, powerful model systems that are widely used in ageing research. We developed an algorithm that enabled us to combine multiple strains of these species from a large number of studies and to extract general trends from relevant results.

Our study indicated that CR and genetic manipulations are effective ways in delaying senescence. The effect pattern of CR is superior to that of genetic manipulation in Caenorhabditis elegans but similar to that of genetic manipulation in Drosophila. Genetic manipulation in mammals faces many problems and risks, and CR, including changes in diet composition, time-restricted feeding, or CR mimetics, could be a more feasible approach for humans. These considerations and our results support CR as a feasible and effective anti-ageing intervention.

Link: https://doi.org/10.1038/s41598-018-24146-z

Comments

The last paragraph de-emphasize if not directly contradicts the title. Probably the title should add "for the time being" and proven to be safe for human use.

Posted by: cuberat at April 16th, 2018 10:02 AM

Everything I have read about caloric restriction is that it increases autophagy, especially with regards to mitochondria. The other recent postings here suggests that mtDNA damage really is the root cause of aging. If so, it is easy to see what caloric restriction would help slow aging a little bit by reducing mtDNA by reducing the amount of calories being consumed at any given time. This, in turn, forces metabolic processes to run more efficiently, which is the very definition of autophagy.

Its interesting that the majority of the populace seems to be going the other direction, towards increased obesity. This, coupled with social "movements" such as fat acceptance, suggests that average human life expectancy will actually decline rather than increase. However, that should not "faze" any of us life extension people since we do not move in the same direction as the rest of society but rather, move in our own direction. Thus, average life expectancy will become as meaningless as average per capita GDP. Ours' will go up. The rest of society will decline.

Posted by: Abelard Lindsey at April 16th, 2018 11:38 AM

@Adelard,

Love your comments/observations. I always known about CR diet for more than a decade. Exercise have been a given and medical experts continue to find benefits of exercist. My favorite phrase (for myself), is "the best part of going to the gym, is leaving it, getting done" But, we must all persevere if we care for our health.

I always say, it is ok to feel hungry, enbrace it:) Buffets are our enemy.

Posted by: Robert at April 16th, 2018 4:47 PM

For anyone who chooses to pursue longevity, what advice is there?
The first would (or should) be to NOT practice anything that takes years away from life. An example would be smoking tobacco takes about 10 years off of lifespan and ruins health span as well as accelerates cosmetic aging (wrinkles).
However, I read of a man in Cuba who smokes cigars and has lived over 100 years. This practice would suggest something mildly toxic (cigar smoking) would activate Nrf2 gene transcription to produce endogenous antioxidants (glutathione, SOD and catalase) which would represent a preconditioning effect against damage caused by strokes, heart attacks, etc.
Population advice on how to live long (e.g. Mediterranean diet) needs to be distinguished from individual advice. There are individuals who live exceptionally long within these populations. Countries at the bottom of the list in regard to life expectancy appear to have malnourished populations. That should be distinguished from calorie restriction, which in the laboratory is accomplished by provision of essential nutrients but limited calories.

In fact, it appears it is not limited calories per se but limited minerals (iron, copper, calcium) that switches genes and favorably extends lifespan. An over mineralization theory of aging has been proposed and never dismissed. Molecules that control over mineralization (chelators) such as IP6 phytate, quercetin (iron), resveratrol (copper) are of primary interest. In general, humans don't biologically age in the first 18 years of life (the growth years) when iron is needed to make more red blood cells (hemoglobin), copper for connective tissue and calcium for bones. But when full growth is achieved, minerals begin to accumulate, first iron and calcium in males. Females menstruate and expel iron in their monthly flow (akin to blood letting) and as baby-makers, this protects them from disease and aging (but induces anemia in about a third). By age 40 men have twice as much iron and 4 times as much calcium stored in their bodies and have double the rate of diabetes, cancer and heart disease as an age-equivalent female. Women who undergo early hysterectomy incur the same rate of disease as males.

There are three speeds of aging: (a) no biological aging during growth years, only chronological (calendar) aging occurs; (b) progressive aging as minerals accumulate, first in males, then females with the onset of menopause; (c) leveling off of the rate of aging that correlates with reaching a steady state of minerals.

Posted by: Bill Sardi at April 22nd, 2018 9:01 AM

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