03.30.08

Lose the Visceral Fat

Posted in Uncategorized at 3:57 pm by Luis

Carrying more visceral fat in your body than you need to get by - the standard result of a life involving too many calories and too little exercise - reduces your longevity. It also greatly increases the chances of your later years being unhealthy, painful and expensive. I've looked at a range of mechanisms by which this happens:

Knowing is half the battle, but putting the work in to shed that fat will pay great dividends over the years. Who wants to be frail and incapacited by diabetes and Alzheimer's at 70, versus fit enough to get out and play a game of tennis whenever you feel like it?

Continuing this examination of reasons not to be overweight, I noticed an interesting paper that demonstrates quite directly the cost of visceral fat (visceral adipose tissue in science-speak) on life span.

Visceral Adipose Tissue Modulates Mammalian Longevity

Caloric restriction (CR) can delay many age-related diseases and extend lifespan, while an increase in adiposity is associated with enhanced disease risk and accelerated aging. Among the various fat depots, the accrual of visceral fat (VF) is a common feature of aging, and has been shown to be the most detrimental on metabolic syndrome of aging in humans.

We have previously demonstrated that surgical removal of visceral fat (VF) in rats improves insulin action, thus, we set out to determine if VF removal affects longevity.

We prospectively studied lifespan in 3 groups of rats: ad libitum fed (AL), 40% caloric restriction (CR) and a group of ad libitum fed rats with selective removal of VF at 5 months of age (VF-). We demonstrate that compared to AL, VF- rats had a significant increase in mean and maximum lifespan and significant reduction in the incidence of severe renal disease.

CR animals demonstrated the greatest mean and maximum lifespan the lowest hazard rate of death as compared to AL rats. Taken together, these observations provide the most direct evidence to date that a reduction in fat mass, and specifically VF, may be one of the possible underlying mechanisms of the anti-aging effect of CR.

This conclusion seems likely - but note that sensibly practicing calorie restriction does much more under the hood than just lower the level of fat in your body. Also note that you don't need to be full-on calorie restricted to lose enough visceral fat to greatly benefit from its absence. The difference between an average, healthy body weight and what passes for the norm in much of the developed world today is large enough to make a big difference to health and longevity in later life.

The body is a complex machine, and like all machines, it ages more slowly if you take better care of it. That much should be common sense.

03.28.08

Leucine and Age-Related Muscle Loss

Posted in Uncategorized at 3:56 pm by Luis

Generally speaking, I'm not a big fan of the sort of hyperaggressive tinkering with supplements that passes for action amongst a large portion of the healthy life extension community. It's highly unlikely to improve significantly on simple exercise, calorie restriction and a sane multivitamin. You have no reliable tool to measure how effective your vitamin regimen is in any case, short of waiting for the necessary decades to see how your long term health goes. Furthermore, solid scientific support is sorely lacking for most of the recommendations you'll see out there - a situation far removed from the vast array of detailed support for exercise and calorie restriction. The waters are muddied by less than ethical marketeers with supplements to sell and money to make; it's very hard for the average fellow to figure out what's what.

Quite aside from all that, how exactly is that tinkering with supplements helping to advance the science of repairing age-related damage? Answer: it isn't. Perhaps your energies are better directed elsewhere...

There are, of course, exceptions to all rules. Leucine supplementation for older folk might just be one of those - although there's a little more work to be done to make an airtight case. Take a look back at the Longevity Meme archives:

Preventing Age-Related Muscle Loss:

Muscle in adults is constantly being built and broken down. As young adults we keep the two processes in balance, but when we age breakdown starts to win. However, adding the amino acid leucine to the diet of old individuals can set things straight again. ... After the age of 40, humans start loosing muscle at around 0.5-2% per year. ... The team of researchers believe that the age-related problem results from defective inhibition of ubiquitin-proteasome dependent proteoloysis, a complex degradative machinery that breaks down contractile muscle protein, and that leucine supplementation can fully restore correct function.

Sarcopenia As Dietary Issue

Sarcopenia, age-related muscle loss, is well known as a common result of aging - and the resulting lack of exercise hastens age-related decline in other ways. ... Since nutritional studies show that many elderly individuals eat less protein than the average person, researchers have reasoned that if the elderly simply increased their protein intake, they might slow down muscle loss -- as long as old age doesn't inherently interfere significantly with the ability to make muscles out of the protein in food. ... We wanted to know if there is some reason your grandmother's body, for example, can't stimulate muscle growth in response to eating the same protein-rich meal that you eat, which might over time contribute to muscle loss ... [however] older bodies are just as good as young ones at turning protein-rich food into muscle.

So, maybe leucine, maybe just protein deficiency. A more recent study caught my eye today; it manages to add support to both sides without actually resolving the question either way:

Supplementation with Dietary Leucine to a Protein-Deficient Diet Suppresses Myofibrillar Protein Degradation in Rats

Muscle mass is regulated by the synthesis and degradation of muscle protein, which in turn are affected by aging, several catabolic diseases, and malnutrition. Amino acids, particularly leucine, are known to stimulate muscle protein synthesis and suppress muscle protein degradation, although their long-term effects are unclear. The objective of our research was to elucidate whether long-term feeding of a protein-free or low-protein diet supplemented with leucine suppresses myofibrillar protein degradation.

...

These results suggest that long-term feeding of leucine suppresses the rate of myofibrillar protein degradation and muscle weight loss in rats fed a protein-deficient diet.

Which supports the use of leucine supplementation in a low-protein diet to slow the rate of muscle loss over time, but doesn't tell us whether simply increasing the amount of dietary protein is a better solution. This is probably of interest to folk practicing calorie restriction, given that their intake of protein is reduced (indeed, reduced protein intake may be the driving mechanism for the beneficial metabolic changes brought on by calorie restriction). As I said above, however, this all needs more weight of research.

A Gentle Reminder That Fat Will Eat Your Mind

Posted in Uncategorized at 3:56 pm by Luis

That excess visceral fat you're carrying causes chronic low-level inflammation, which damages you in all sorts of ways. One of those ways is atherosclerosis, which tends to up and kill you without warning. In fact, eating all the food required to gain a large amount of visceral fat causes a feedback loop in your metabolism that spirals down into insulin resistance and diabetes - both of which make the effects of having a lot of visceral fat that much worse and that much more rapid.

But that extra fat won't just make you much more prone to be frail, and it won't just try to kill you - it'll also eat your mind. Researchers are coming to view Alzheimer's disease as analogous to diabetes, a result of lifestyle choices for most, touching on many of the same metabolic processes as diabetes, and the risk factors seem to be much the same.

Big Bellies Linked to Alzheimer's Disease:

The study of more than 6,000 people found the more fat they had in their guts in their early to mid-40s the greater their chances of becoming forgetful or confused or showing other signs of senility as they aged. Those who had the most impressive midsections faced more than twice the risk of the leanest.

Surprisingly, a sizable stomach seems to increase the risk even among those who are not obese, or even overweight

...

The research is the latest evidence that fat in the abdomen is the most dangerous kind. Previous studies have linked the apple-shaped physique to a greater risk of diabetes, heart disease and even cancer. Researchers suspect that those fat cells are the worst because of their proximity to major organs. They ooze noxious chemicals, stoking inflammation, constricting blood vessels and triggering other processes that might also damage brain cells.

"There is a lot of work out there that suggests that the fat wrapped around your inner organs is much more metabolically active than other types of fat right under the skin," Whitmer said. "It's pumping out toxic substances. It's very potent toxic fat."

Another excellent reason to take care of the health basics - a responsible level of diet and exercise - before your body sabotages your mind. The longer you leave it, the more damage you're creating, and the more you're cutting from your likely healthspan.

03.26.08

On Biofabrication

Posted in Uncategorized at 3:55 pm by Luis

Researchers are working their way closer to a grail of tissue engineering: a fabricator that can print out living organs in three dimensions just like the rapid prototyping devices used today in a variety of industries. Plastics and inks become cells and biomaterials, and the whole works much the same way. Organs are many magnitudes more complex in structure than the plastic prototypes turned out by fabricators in the design industry, but the cells used to build those organs can - in theory - be induced to do most of the small-scale organization for you. Roland Piquepaille notes one of the latest technology demonstrations:

"We will never be able to print a liver with all of its many details," says Forgacs. "But it is not necessary. If you initiate the process, nature will do it for you."

According to MU, "the team used bio-ink particles, or spheres containing 10,000 to 40,000 cells, and assembled, or 'printed,' them on to sheets of organic, cell friendly 'bio-paper.' Once printed, the spheres began to fuse in the bio-paper into one structure." Nature adds that "when they printed out cardiac and endothelial cells, the cells fused into a tissue after 70 hours, and began beating in time like regular heart tissue after 90 hours."

Nature also explains why this project is different from previous ones. "What makes this work different from that done in most other tissue-engineering labs is that Forgacs's team does everything without a scaffold - they don’t start with an object shaped like the tissue or organ they are aiming to create, but instead plan to print the whole thing from scratch, from the vasculature up. This should make it easier to print any type of organ, they say, as they don’t have to develop different scaffolds for each tissue type. 'Often when you implant a scaffold you get inflammation,’ says Forgacs.'"

Researchers are still building the components of organs in the technology demonstrations - we're a few years away from fabrication of even "simple" organs, such as the heart or liver. As I've noted previously, the big hurdle of the moment is getting the blood vessels - the vasculature - right. Blood transport is vital to building living tissue of any meaningful size, and it's a hard problem if all the blood vessels, from microscopic capillary networks on up, have to be designed by hand into the tissue you're printing.

On Attitudes Towards Longevity

Posted in Uncategorized at 3:55 pm by Luis

Some interesting material from a scientific study of attitudes to healthy life extension and enhanced longevity is posted to Cryonet:

The age of the respondent was related to life-extension attitudes [with] the older respondents tilting in the pro-longevity direction.

Pro-longevity attitudes were strongest in the separated-divorced group and weakest in the single group.

From a utilitarian, economic action viewpoint, that is much as I would expect. I think there's ample circumstantial evidence to suspect that those who claim to be fine with aging and dying will mostly change their minds when they get there. The unpleasant future is all to easily hand-waved away for another day - until that day finally comes home to roost.

The study presented subjects with a range of positive and negative viewpoints on healthy life extension. The viewpoints vary widely in validity, with those on the economic side of the house being particulary bad, but I don't think that's too important when it comes to drawing conclusions from the reactions of study participants:

I. Personal Emotional Rejection (PER) reflects a harsh rejection of life extension with endorsement of items focused on pointlessness and waste, and contrary-to-nature aspects of extending life span. Other items reflect the personal cost of life extension (e.g., delaying commitments or prolonging goals, inducing boredom).

II. Utopian Vision (UV) points to the many advantages of life extension for older people and for society at large.

III. Social Economic Burden (SEB) highlights the economic burdens on the individual and the health-care system flowing from life extension. The highest loading items stress preference for health over longer life and a fear of financial dependency for the individual, and exhaustion of resources for the society.

Age was significant for each of the factors. ... The older the adult, the more likely is he or she to reject the harsh negativity toward life extension reflected by the items loading on factor I. Correspondingly, chronological age is positively associated with endorsement of items that promise a Utopian future with life extension (Factor II). Finally, the outcome for Factor III is somewhat counterintuitive as we observe that older adults are significantly more disposed to endorse anti-longevity items. These items concern the added costs of health-care and social welfare and hence raise the possibility of exhaustion of financial resources.

That last point only reinforces my conviction that economic ignorance is one of the greatest threats to the future of healthy life extension (and indeed to all meaningful advancements in technology). It is a strange world when so many believe that more healthy people working away to produce value and trade with one another will somehow make us all poorer:

The points that found the most favor in the study might lead us to a little more optimism, however:

Of the positive survey items, these were the most stable across the studies:

Longevity improving life more time for goals
Extending life giving respect to old age
Longevity research as duty to future generations
Long Term Relationship (LTR) quality will increase with longevity
Society will benefit from greater wisdom
Increase budget for this research

Other positive items from the LEQ:

Favor longevity research even if product unaffordable
Extend life to have more leisure time
Estimate satisfaction greater at age 110 than 75
Families benefit from cross-generation interaction

I'm sure you'll recognize a number of these in past material produced by longevity advocates, myself included. Biomedical gerontologist Aubrey de Grey in particular has argued for duty to those yet to live - in his view, who are we to decide that our grandchildren's lives must be as short as our own? By failing to heed the moral imperative to longevity research, we condemn future generations to have no choice in their own longevity.

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