Since my previous post was mostly background on IGF-1 and did not present much in the way of opinions in relation to longevity, pro or con, I wanted to address the pro and con with some studies in this post. So far there does seem to be a general conclusion that IGF-1 reduction seems to play a part in calorie restriction, but the magnitude has yet to be determined.

The first paper I want to mention considers the possibility of IGF-1 affecting mortality in general, and not only in the confines of anti-aging research. I wanted to present this because while it is possible lowering IGF-1 may help longevity, moderate or even somewhat elevated levels may not be a health risk. Maybe, maybe not. Lots of maybes here.

This study sought to analyze IGF-1 levels with overall mortality. The authors do note that the IGF-1/ IGFBP-3 relation to human disease is complex. High IGF-1 levels have been correlated with a moderate increase of cancer risk, but the opposite is seen with heart disease. The data for this study was obtained from the Third National Health and Nutrition Examination Survey Mortality Study that passively followed participants from 1988 to 1994. The survey included a physical exam, lab work, and questionnaires. At randon, 6226 people were selected for analysis of IGF-1 and IGFBP-3 levels.

Additional variables taken into consideration: sex, race, smoking status, alcohol use, and BMI. The authors note that IGF-1 and IGFBP-3 often decline with age, and most of the fatalities occurred in the older subset. In the end, they concluded there was no significant association between IGF-1 or IGFBP-3 and all cause mortality risk. The main limitations of this study, as described by the authors, is that there were few deaths overall. Since this study is looking at mortality risk, if only a few people died, then observations become limited. They note that less than 200 deaths out of over 6000 people occurred. Also, there was only one reading of IGF-1/IGFBP-3 levels, so any change was not observed.

NOTES/ISSUES: The main issue with this study is that it is looking at OVERALL mortality, not health or diseases. So, for example (this is purely theoretical so I can make a point), say 4000 people out of 6000 got cancer and all had high IGF-1 levels, but only 10 died. Their data would only consider the 10 that died. Also, since they only used one data point per individual, potentially important fluctuations were not observed. Because of the possibility of very skewed data, I personally cannot stand behind this study as indicative that high IGF-1does not pose a mortality or health threat. However, I’m not saying it doesn’t; I just can’t use this study to come to my final conclusion.

Moving along…

I only had access to the abstract for this paper, but I felt it was worth mentioning. Obviously, I can not critique the methods, but wanted to present it nonetheless. The researches note animal and invertebrate models have established the IGF-1 signaling pathway as an aging modulator with research showing that reduced exposure to IGF-1 is associated with extended life spans.

Also noted: reduced IGF-1 activity in adulthood is associated with an an increased risk of developing cardiovascular disease, diabetes, osteoporosis, and neurodegenerative diseases while elevated IGF-1 has been linked to cancer risk.

The author theorizes of the possibility that lower levels of IGF-1 in adulthood followed by higher levels of IGF-1 later in life may be the  most beneficial.

NOTES/ISSUES: All I really want to say here, since I can’t critique the full study, is based on the complexity of IGF-1 signaling, I find it difficult to associate a definite causation to the correlation between high or low values in terms of diseases and cancer. I feel that in these cases, the IGF-1 is related to the nature of the disease rather than a part of the cause. Remember, correlation does not equal causation. This signaling pathway is very complex, and while data collection on correlation to disease is needed, the results are not so black and white.

To address the correlation of lower levels of IGF-1 with heart disease, diabetes, osteoporosis, and neurodegenerative diseases, I feel that most of these issues are mitigated by a healthy lifestyle that may or may not include CR. So, in the case of a health lifestyle, how does low levels of IGF-1 affect the body? This is the question!

Same consideration with the cancer risk. Since CR and/or a healthy lifestyle can lower ones cancer risk, how much will higher levels of IGF-1 affect the body?

Additional Thoughts:

I am realizing how much the complexity of the system muddles data. Since we know little about the mechanisms behind the longevity effects seen in animals, trying to apply these results to humans becomes difficult to do in a tangible rather than speculative way. The correlations for high or low IGF-1 so far seem to lack proof in causation. Heck, even dismissing causation and taking the approach that for a given condition low/high IGF-1 levels can aggravate a disease is difficult to prove. I just see correlation that has been isolated from a sea of affecting variables.

I want to see studies of IGF-1 levels in healthy individuals. The CR study in the previous IGF-1 post showed many CR people without low IGF-1 levels but with other bio-markers of amazing health. What I would like to see is CR people who keep low protein to induce low IGF-1 levels compared to CR people with moderate/high protein to induce moderate/high IGF-1 levels. I want to see the difference in bio-markers over the period of at least a year. This, sadly, is being research greedy. The logistics of such a study are difficult, although not impossible.