13 replies to this topic

[Dorho]

Here are some fun facts:

-there are more bacterial cells in human body than human cells. Some bacteria, like H pylori, increase suspectibility to cancer and other age-related diseases.
-at least 8% of human genome comprises of endogenous retroviruses (ERVs), recent findings indicate that there are also non-retroviral virus insertions. ERVs are suspected to cause cancers and autoimmune diseases such as schizophrenia and multiple schlerosis.
-about 42% of human genome is comprised of retrotransposons, and about 2-3% of DNA transposons. Transposons, "jumping genes", may cause hemophilia, immunodeficiency, porphyria and predisposition to cancer.
-very little is known about some exotic life forms such as nanobacteria, nanobes and prions, which are probably present in humans in a lot higher numbers than currently is thought.

With all this knowledge, one would think that microbial life forms would be under greatest scrutiny in anti-aging circles, yet I have not noticed such an emphasis. Any thoughts on this?

Edited by Dorho, 04 April 2010 - 06:27 PM.

[s123]

You read the GRG mailing list? Because this was just pointed out in an e-mail yesterday.

The bacterial theory of aging was proposed by Elie Metchnikoff. However later research found that animals without bacteria in their gut didn't live longer (and sometimes lived less long). However more recently the connection between aging and inflammation due to chronic infection has been proposed to contribute to aging. Interesting is a recent investigation published in Plos One that showed that amyloid beta functions as a antimicrobial peptide. The paper speculated that amyloid beta overproduction in the brain of Alzheimers patients could be part of an immune response against a chronic infection.

Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, and Moir RD. The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide. PLoS ONE, 2010, 5(3): e9505.

[Dorho]

You read the GRG mailing list? Because this was just pointed out in an e-mail yesterday.

The bacterial theory of aging was proposed by Elie Metchnikoff. However later research found that animals without bacteria in their gut didn't live longer (and sometimes lived less long). However more recently the connection between aging and inflammation due to chronic infection has been proposed to contribute to aging. Interesting is a recent investigation published in Plos One that showed that amyloid beta functions as a antimicrobial peptide. The paper speculated that amyloid beta overproduction in the brain of Alzheimers patients could be part of an immune response against a chronic infection.

Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, and Moir RD. The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide. PLoS ONE, 2010, 5(3): e9505.

Thanks, that's all very nice info. I'm not on the GRG mailing list and I don't even know what GRG stands for, but I sure would like to know.

Mammals have coevolved to live in symbiosis with gut bacteria, which explains why we are better off with good intestinal bacteria than without bacteria at all. It's a bit worrysome though that there are also harmful bacteria in the gut and different bacterium species are able to exchange genes, meaning that 'bad' genes may end up in otherwise beneficial bacteria, and the new bacterium type then either multiplies or dies off, depending on what natural selection has to say. As an example, the highly dangerous E coli strain O157:H7 was born when a typical colibacterium received genes that enabled it to produce shiga-like toxins.

[s123]

Thanks, that's all very nice info. I'm not on the GRG mailing list and I don't even know what GRG stands for, but I sure would like to know.

Gerontology Research Group.
http://www.grg.org/

[Dorho]

Scientists who conducted a recent study on the connection between 'Long Terminal Repeats' and Hodgkin's lymphoma, suspect that these retroviral remains may drive the growth of other kinds of cancers too. Physorg's entry of the new study: http://www.physorg.c...s192013975.html

Most people probably don't consider retrovirus insertions as examples of life, but as somewhat autonomous replicators, they deserve more attention than they are now getting, imo.

[Logan]

Lithium and St. John's Wort both have antimicrobial properties.

[erzebet]

Here are some fun facts:

-there are more bacterial cells in human body than human cells. Some bacteria, like H pylori, increase suspectibility to cancer and other age-related diseases.
-at least 8% of human genome comprises of endogenous retroviruses (ERVs), recent findings indicate that there are also non-retroviral virus insertions. ERVs are suspected to cause cancers and autoimmune diseases such as schizophrenia and multiple schlerosis.
-about 42% of human genome is comprised of retrotransposons, and about 2-3% of DNA transposons. Transposons, "jumping genes", may cause hemophilia, immunodeficiency, porphyria and predisposition to cancer.
-very little is known about some exotic life forms such as nanobacteria, nanobes and prions, which are probably present in humans in a lot higher numbers than currently is thought.

With all this knowledge, one would think that microbial life forms would be under greatest scrutiny in anti-aging circles, yet I have not noticed such an emphasis. Any thoughts on this?

Sally Fallon is the first one that made me think of this aspect; her solution was to create competition between germs - so to consume foods high in probiotics.
Pasteur although established the germ theory of disease, concluded that"The germ is nothing; the terrain is everything" as life is competition for resources.

I said these because the mainstream approach of combating germs might do more harm than good according to the hygiene hypothesis.

[Sillewater]

Some interesting reviews, does anyone have access?

Curr Drug Metab. 2009 Jan;10(1):41-54.
Non-digestible food ingredients, colonic microbiota and the impact on gut health and immunity: a role for metabolomics.
Jacobs DM, Gaudier E, van Duynhoven J, Vaughan EE.

Gut Pathog. 2009 Dec 7;1(1):21.
A hundred-year-old insight into the gut microbiome!
Aziz RK.

Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, 11562 Cairo, Egypt. ramy.aziz@salmonella.org.
Abstract
ABSTRACT: As the National Institutes of Health-funded Human Microbiome Project enters its second phase, and as a major part of this project focuses on the human gut microbiome and its effects on human health, it might help us to travel a century back in time and examine how microbiologists dealt with microbiome-related challenges similar to those of the 21st century using the tools of their time. An article by Arthur I. Kendall, published in The Journal of Biological Chemistry in November 1909 (Some observations on the study of the intestinal bacteria J Biol Chem 1909, 6:499-507), offers a visionary insight into many of today's hot research questions.

[Medical Time Travel]

Human Microbiome Project (HMP)

http://hmp.jcvi.org/

http://nihroadmap.ni...initiatives.asp

WCG HPF2 is folding for the HMP:

http://www.worldcomm...pf2/overview.do

http://www.worldcomm...28940_offset,20

New BBC article covering the issue:

http://news.bbc.co.u...lth/8695673.stm

[ImmInst]

There's a range of research to indicate that gut bacteria are important in the relationship between metabolism and aging, though the situation in higher animals is probably far more complex than in nematode worms: "A powerful approach to understanding complex processes such as aging is to use model organisms amenable to genetic manipulation, and to seek relevant phenotypes to measure. Caenorhabditis elegans is particularly suited to studies of aging, since numerous single-gene mutations have been identified that affect its lifespan; it possesses an innate immune system employing evolutionarily conserved signaling pathways affecting longevity. As worms age, bacteria accumulate in the intestinal tract. However, quantitative relationships between worm genotype, lifespan, and intestinal lumen bacterial load have not been examined. We hypothesized that gut immunity is less efficient in older animals, leading to enhanced bacterial accumulation, reducing longevity. To address this question, we evaluated the ability of worms to control bacterial accumulation as a functional marker of intestinal immunity. ... We show that as adult worms age, several C. elegans genotypes show diminished capacity to control intestinal bacterial accumulation. We provide evidence that intestinal bacterial load, regulated by gut immunity, is an important causative factor of lifespan determination; the effects are specified by bacterial strain, worm genotype, and biologic age, all acting in concert. ... In total, these studies focus attention on the worm intestine as a locus that influences longevity in the presence of an accumulating bacterial population. Further studies defining the interplay between bacterial species and host immunity in C. elegans may provide insights into the general mechanisms of aging and age-related diseases."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22452899

View the full article

[ihatesnow]

http://www.genome.gov/27549400
http://benchmarks.ca...te-to-cancer-3/
http://www.newswise....d-breast-cancer
http://www.forbes.co.../?feed=rss_home

[ihatesnow]

:
www.genome.gov/27549400
benchmarks.cancer.gov/2012/06/...
www.newswise.com/articles/expl...
www.forbes.com/sites/matthewhe...
the human microbiome project commonfund.nih.gov/hmp/

[reason]

We possess a very large and diverse set of bacteria inside our bodies, and they play a vital role in process such as digestion. In effect they are the first link in the chain that leads from diet to metabolism to the pace of aging: a large portion of how environment influences natural variations in life expectancy. Researchers are still only in the very early stages of gaining a complete picture of human aging in terms of metabolism, genes, gene expression, and cellular mechanisms. It is enormously complex, but very little of this ongoing work has anything to do with our symbiotic bacteria - so by comparison next to nothing is known about how the intestinal microbiome fits into the big picture, and not much of a grasp on how important it might be in aging.

(As an aside: as soon as the research community can develop medical technologies like those envisaged in the Strategies for Engineered Negligible Senescence (SENS), natural aging and ways to influence it become a quaint old-time sideshow. We will be able to reverse the progression of aging, so why bother with those small details? To my mind that means we should all treat these discussions like a quaint old-time sideshow today, and focus more on how to make SENS happen faster).

But back to the plot: think about calorie restriction and the degree to which it (a) affects health and longevity, and (b) seems to hinge on levels of certain essential amino acids transported to cells. In that context, it seems likely that changes or differences in gut microbe populations - some of which are preprocessing your dietary intake - could have some influence. But again, there isn't much to go on in terms of solid data in comparison to research aimed at figuring out our own cells. You might look at these posts from the archives as a starting point:

• Investigating Intestinal Bacteria and Aging in Nematodes
• Becoming Aware of the Influence of Bacteria Upon Aging and Longevity
• Aging and Bacteria in the Body
• Intestinal Bacteria and Ageing

My attention was caught today by a post on changes in our gut microbiome over the past century - they have been very large indeed, now matter which causative mechanism you think might be the likely culprit:

Too Many Antibiotics? Bacterial Ecology That Lives On Humans Has Changed in Last 100 Years

[Researchers] analyzed microbiome data from ancient human fecal samples collected from three different archaeological sites in the Americas, each dating to over 1000 years ago. In addition, the team provided a new analysis of published data from two samples that reflect rare and extraordinary preservation: Otzi the Iceman and a soldier frozen for 93 years on a glacier.

"The results support the hypothesis that ancient human gut microbiomes are more similar to those of non-human primates and rural non-western communities than to those of people living a modern lifestyle in the United States. From these data, the team concluded that the last 100 years has been a time of major change to the human gut microbiome in cosmopolitan areas."

The past hundred years has also been a time of greatly increased life span expectancy, both at birth and adult life expectancy at any age. There are plenty of obvious candidate mechanisms to point to when explaining these gains: control of infectious disease; improved medical technology across the board; rapidly increasing wealth and all the benefits that brings to the individual.

So there is no great incentive or missing cause that might drive one to go digging around in the microbiome of the gut in search of the degree to which changes there might influence life span. But it is interesting to speculate on that topic in advance of the studies that might provide an answer one way or another - which I would expect to require a great deal of time and work, given that the effects of medicine and wealth are comparatively large. Teasing out smaller effects from population studies is a challenging task.

<br> <br>View the full article

[xEva]

Thanks for the interesting article This subject interests me greatly.

I have a question. On what data you base the following statements:

... bacteria inside our bodies... play a vital role in process such as digestion.

In effect they are the first link in the chain that leads from diet to metabolism...

...it seems likely that changes or differences in gut microbe populations - some of which are preprocessing your dietary intake....

You make it sound as if we are some ruminants or termites who wholly depend on their gut microbiome for digestion. Humans on antibiotics digest their food just fine (and some even better than before a course of antibiotics). For digestion we mostly rely on the enzymes produced by our pancreas and the small intestine; and while microbes certainly contribute a variety of metabolites --both good and bad-- their influence on our digestion per se is negligible (even though, true, some were implicated in aggravating the rampant in the western world hyperphagia and the resultant epidemic of obesity -- hardly a positive in this context).

As far as CR goes, I know for a fact that the population of the gut bacteria changes. First of all, their sheer numbers go down dramatically, which is a good thing: there is less policing for the immune system to do and less metabolites for the liver to process.

The worst of the metabolites produced by our gut commensals is lipopolysaccharide (LPS endotoxin). It does get absorbed into the bloodstream and it is the job of the liver to remove it. I read that patients with advanced liver disease are routinely given antibiotics, not because they have an infections, but to keep their gut bacteria --and their toxic metabolites-- down.

http://ajcn.nutritio.../86/5/1286.long

...bacterial endotoxin [lipopolysaccharide (LPS)] is a potently inflammatory bacterial antigen that is present in large quantities in the human gut (8). Endotoxin circulates in the plasma of healthy human subjects at low concentrations (between 1 and 200 pg/mL; 9&ndash;13), yet it is increasingly considered to play a proatherogenic role (reviewed in reference 14). Elevated concentrations of circulating LPS correlate well with an increased atherosclerosis risk (9), whereas in vitro studies have shown LPS to potently up-regulate atherogenic gene expression (15), cholesterol retention, and foam cell formation (16).

I wanted to bring this to your attention, because IMO you exaggerate the positive impact of gut bacteria on our health and appear largely unaware of the negatives. Overall, on the balance, we do better without them then with them, and people on antibiotics, for various reasons, prove it. (Of course, it is impossible in practice to live 'without them', but that would be another topic.)