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Health news:
 
June 2010 - Dec 2013

Minimizing breast cancer risk

May 2010

Time to move beyond salt ?

Salt hypothesis vs. reality

Is sodium bad?

April 2010

Salt studies: the latest score

From Dahl to INTERSALT

Salt hypothesis' story

March 2010

Salt war

Do bone drugs work?

Diabetes vs. drugs, 3:0?

February 2010

The MMR vaccine war: Wakefield vs. ?

Wakefield proceedings: an exception?

Who's afraid of a littl' 1998 study?
 

January 2010

Antibiotic children

Physical activity benefits late-life health

Healthier life for New Year's resolution

 

December 2009

Autism epidemic worsening: CDC report

Rosuvastatin indication broadened

High-protein diet effects

 

November 2009

Folic acid cancer risk

Folic acid studies: message in a bottle?

Sweet, short life on a sugary diet

 

October 2009

Smoking health hazards: no dose-response

C. difficile warning

Asthma risk and waist size in women

 

September 2009

Antioxidants' melanoma risk: 4-fold or none?

Murky waters of vitamin D status

Is vitamin D deficiency hurting you?

 

August 2009

Pill-crushing children

New gut test for children and adults

Unhealthy habits - whistling past the graveyard?

 

July 2009

Asthma solution - between two opposites that don't attract

Light wave therapy - how does it actually work?

Hodgkin's lymphoma in children: better alternatives

 

June 2009

Hodgkin's, kids, and the abuse of power

Efficacy and safety of the conventional treatment for Hodgkin's:
behind the hype

Long-term mortality and morbidity after conventional treatments for pediatric Hodgkin's

 

May 2009

Late health effects of the toxicity of the conventional treatment for Hodgkin's

Daniel's true 5-year chances with the conventional treatment for Hodgkin's

Daniel Hauser Hodgkin's case: child protection or medical oppression?

April 2009

Protection from EMF: you're on your own

EMF pollution battle: same old...

EMF health threat and the politics of status quo
 

March 2009

Electromagnetic danger? No such thing, in our view...

EMF safety standards: are they safe?

Power-frequency field exposure
 

February 2009

Electricity and health

Electromagnetic spectrum: health connection

Is power pollution making you sick?

January 2009

Pneumococcal vaccine for adults useless?

DHA in brain development study - why not boys?

HRT shrinks brains

NEWS ARCHIVE
2009
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November 2009

 Sweet, short life on a sugary diet

Imagine you are a tiny little worm, happily feeding on bacteria, and also got lucky to have some steady sugar added to your diet. Everything looks - or should we say tastes - great ... until it's time to go. The bad news is that for you it comes 3-4 days sooner than for your counterparts without extra sugar in their diet; they get to live all of their 18-day lifetimes.

This is a true story: it actually happened to undisclosed number of C. elegans (Caenorhabditis elegans, or roundworm), in an experiment by Dr. Cynthia Kenyon, molecular geneticist at the University of California, San Francisco. Worms who had small amount of glucose added to their daily diet, had their lifespan cut short by about 20%.

What did sugar do to them? A simplified scheme may look like this:

elevated blood glucose level stimulates production of insulin, needed for its entry into the cells

cells moderate overflow of glucose by developing lowered sensitivity to insulin

this further elevates both glucose and insulin blood levels, but cells' glucose supply may become insufficient due to their insulin insensitivity

chronically elevated insulin level creates complex signals affecting multiple metabolic pathways; among the consequences seen on C. elegans was downregulation of glycerol-transporting aquaporin channels (aquaglyceroporins), possibly restricting this alternate cellular fuel source as well

insulin signaling pathways include effects on genes, as well as special proteins - so called transcription factors - controlling gene expression; elevated insulin level promotes higher oxidation states, while reduced insulin promotes protective, stress-resistant metabolic states akin to those of dauer (hibernation-like mode of worm's existence during development induced by unfavorable conditions), but without actually going into it

The key gene involved in dauer-related processes in the worm is
Daf-2
(Dauer formation 2) gene, which does it by modulating endocrine signaling. It is, however, only one of the players involved; to exert its influence, it needs coordinate action of other regulatory proteins downstream, such as Daf-16, and HSF-1 heat shock factor. Worms without these two proteins were not affected by elevated glucose level.

In fact, it is a set of genes upregulated by Daf-16 that are directly involved in life extension. When their activity is purposely inhibited, the result is up to 20% reduction in lifespan, without exposure to elevated glucose levels.

On the other hand, suppressing Daf-2 activity will

more than double worm's average lifespan -

as Kenyon's studies from 1990s show - but not if glucose is added to its diet. Obviously, the final outcome is determined by the specifics of individual biochemistry, both, those significantly influenced by environmental factors (i.e. elevated glucose intake), and those that are not.

So how this worm story relates - if at all - to us humans?

Well, we're not all that different. Worm's Daf-2 gene is its lone member of the insulin receptor family; it belongs to the same family that our insulin receptor (IR) and insulin-life growth factor receptor (IGF-1R) do. To a good extent, its functions overlap with those of the other two.

Worm's Daf-16 gene, downstream from Daf-2, is a FOXO protein subgroup member. FOXO proteins are gene transcription factors belonging to the Forkhead Box, or FOX family of proteins, with the "O" subgroup sharing the characteristic of being influenced by the insulin/PI3K/Akt signaling pathway. The FOXO protein transcription factors in mammals, including humans, are FOXO 1, 3, 4 and 6. They were first identified in human cancer cells. Their basic functions is to

modulate genetic activity according to environmental inputs.

Activity of both, Daf-16 and mammalian FOXO proteins is directly influenced by the insulin/PI3K/Akt signaling pathway. Akt (serine-threonine kinase activated by PI3K, phosphoinositide 3-kinase or PDK1, phosphoinositide-dependent kinase 1) mediated phosphorylation of the FOXO proteins, resulting from intensified insulin and/or insulin growth factor signaling, causes them to move from cell's nucleus to the cytoplasm, preventing them from transcribing to their target genes.

Phosphorylation of FOXO proteins by other protein kinases (kinase=type of regulatory proteins), like JNK and Mst1, as a response to increased oxidative stress, has the opposing action, causing FOXO proteins to move from cytoplasm to cell's nucleus, where they can transcribe to their target genes.

What is it, exactly, that they do?

FOXO proteins modulate expression of genes regulating vital cellular processes like apoptosis (programmed cell death), cell-cycle progression, and oxidative protection, by activating free radical quenchers catalase and manganese-dependant superoxide dismutase (MnSOD) and by facilitating DNA-repair process. They are also involved in cellular differentiation, glucose metabolism and energy homeostasis, even in upregulation of neuropeptides in hypothalamus. More on their functions is to come, as more FOXO proteins target genes will be identified.

To make long story short,

you don't want your regulatory FOXO proteins possibly
kicked out of the nucleus due to chronically elevated
glucose levels.

They're too important.

The activity of worm's FOXO protein, Daf-16, prolongs lifespan by modulating gene expression toward increased resistance to oxidative stress, DNA damage and pathogens (bacteria that the worm eats ultimately overwhelm and eat up the worm; worms on glucose-enhanced diet get weaker and eaten up sooner). Inhibiting worm's insulin receptor, Daf-2, or PI3K, results in up to tripled lifespan - but only when Daf-16 is active.

In mice, inhibiting functions of insulin receptor or insulin growth factor 1, both downregulating mammalian FOXO proteins - and more so when glucose level is elevated - results in up to 30% life extension.

Chances are, our longevity also benefits from FOXO proteins doing their job. And a seemingly innocent attraction to sweets - among other environmental inputs - may as well be triggering an archaic cellular response deeply imbedded into the "blueprint" of our cells, compromising their function and

making the body less efficient, more vulnerable and perishable.

In addition, the role of FOXO proteins in apoptosis, cell-cycle progression and DNA repair makes them a likely balancing force between the two opposites with the same roots: cellular longevity and cancerous growth. As mentioned, they were first identified in cancer cells, at chromosomal translocations (i.e. fragments of broken chromosomes cross-linked to other chromosomes).

Knowing what we do about FOXO proteins function, they were there to help repair damaged DNA; the extent of damage indicates that too many of them were absent, sitting idle in the cytoplasm, possibly - at least in part - due to chronically elevated glucose level.

Anyway, Dr. Kenyon took the short sweet lives of C. elegans very seriously. She dumped sweets and switched to low-glycemic diet. In her own words, she feels great now - as if she is a kid again.

Sugar is sweet, but life is sweeter...

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