March 21, 2008

A Lesson from the Worms

Two related findings have come out recently that point to the role of insulin and insulin-like growth factor (IGF) in longevity.

One was the finding from the Albert Einstein School of Medicine's Longevity Study that longevity was associated, at least in females, with the presence of a gene that decreased the secretion of IGF. They discovered this after noting that female offspring of female centenarians tended to be about an inch shorter than normal.

Functionally significant insulin-like growth factor I receptor mutations in centenarians. Yousin Suh et al.

The other was the finding in the worm, c. elegans, that, as Science Daily reports, "insulin inhibits a master gene regulator protein known as SKN-1, and that increased SKN-1 activity increases lifespan. SKN-1 controls what is called the Phase 2 detoxification pathway, a network of genes that defends cells and tissue against oxidative stress -- damage caused by elevated levels of free radicals (byproducts of metabolism) -- and various environmental toxins."

Science Daily: Insulin Has Previously Unknown Effect that has Role in Aging and Lifespan

I was a subject in the centenarian study since my dad was a centenarian, but because they only looked at the genes of the children of female centenarians I don't have any data about whether I carry this gene. Still, this is the first time I've ever heard anything suggesting that all those years of being called "shrimp" on the playground and of always being the shortest kid in my class might pay off, big time.

Scientists have long known that you can extend the lifespan of most organisms by cutting way back on their food. But perhaps these findings mean the eat-less longevity approach it isn't about cutting down on food so much as it is about cutting back on foods that stimulate insulin secretion. Those foods are, of course, carbohydrates and to a much lesser extent proteins.

So once again, we get a very good reason to embrace eating fat and back off those "healthy grains and fruit" nutritionists insist are "good for us."

But what about those of us, self-included, who inject insulin or take drugs that increase insulin production? Well, it's a matter of trade offs. We know that high blood sugars damage our bodies, so whatever longevity benefits there might be in cutting back on insulin are going to be balanced by the life-shortening effects of clogging our capillaries and killing our nerves when our blood has become glucose-laden sludge.

We should also be very careful about taking drugs that increase our insulin resistance, most notably the SSRI antidepressants. These drugst raise insulin resistance and hence raise insulin levels in people who take them, no matter what their blood sugar level might be.

What lowers insulin resistance?

1. Keeping blood sugars at normal levels. When your blood sugar goes up to 200 mg/dl you get a lot more insulin resistant no matter what your fundamental level of insulin resistance might be.

2. Exercise--for many people. (Not all, but that's another blog post!) But be careful about what kind of exercise you pursue. If you work up a huge appetite when you exercise and end up eating more than you otherwise would have, you'll undo any benefit of that exercise because more food will mean more insulin. This may be one reason that brisk walking or modest amounts of biking, which aren't likely to cause dramatic blood sugar swings and the resulting hunger might be more healthy, long term, than more heroic exercise routines.

3. Weight loss in people who are seriously overweight. And if you are insulin resistant, the research suggests that you are much more likely to lose weight on a low carb diet, though the same research suggests that people who are NOT insulin resistant can lose equally well on any diet that reduces calories.

4. Metformin.

5. Avandia and Actos, though they appear to cause so many undesirable side effects long term, including osteoporosis, that they are probably not going to increase your longevity.

If you are doing all you can and are, like many people with diabetes still insulin resistant and still dependent on large amounts of insulin to control your blood sugar, should this data ruin your day?

No. One other thing that the Albert Einstein Med School longevity research has proven is that longevity is mostly a matter of getting lucky genes. In a CNN interview, Dr Barzilai, the chief researcher on the longevity project said in regards to the population of centenarians he's following, "We don't have yoga teachers. We don't have vegetarians. Thirty percent of them were overweight or obese in the 1950s. We don't have anybody that's exercising. There are several people who smoked. So for those people, the environment didn't matter. They had something else that we think is genetic."

So taking heroic efforts to extend your own life is usually futile. Don't forget the fate of Dr. Roy Walford, the most famous proponent of the Life Extension diet, dead at 79 of ALS. Or my mom, whose fasting blood sugar at age 92 is 81 but who got dementia from cancer chemotherapy a decade ago. It isn't all about blood sugar. . .


Anna said...

Nice to see research using c. elegans in your post. We have a fondness for this worm in our household; my husband's apoptosis research uses this worm quite a bit.

Anonymous said...

My grandmother was 4' 10" tall and lived to be a little over 101. She used to eat bologna and onion sandwhiches for lunch and always ate butter. She always said "no fat, no taste". Being male I probably won't live that long, but you never know.