Growth Hormone and Aging Continued: IGF-1 Levels and Longevity

As suggested in the last post growth hormone and its downstream partner IGF-1 have a somewhat controversial standing with regard to aging and longevity. Although observations of animals seem to suggest GH/IGF-1 shortens lifespan, such observations are not as clear with humans. Additionally, while GH/IGF-1 does seem to promote cancer it also to seems to prevent cardiovascular disease, depending on the context.

With that in mind I thought it would be informative to look at prospective cohort studies to see if more physiologically relevant deviations in IGF-1 are associated with variations in mortality rates.

In the Cardiovascular Health Study no association between IGF-1 and mortality was found in 1112 adults over the age of 65 (3). Mortality was non significantly higher in the group with the lowest IGF-1 levels.

The Rancho Bernardo Study examined the relationship between IGF-1 levels and death in 1185 adults between the ages of 51 and 98 (2). For every 40ng/mL increase in blood levels of IGF-1 risk of ischaemic heart disease (IHD) mortality was decreased by 38%. However no association between IGF-1 levels and total mortality was observed.

The Framingham Heart Study also observed a reduction in IHD mortality as well as a reduction in total mortality with increasing IGF-1 in 525 community dwelling adults between the ages of 72 and 92 (1). Mortality was lowest in subjects with the 2nd highest IGF-1 levels (out of 4 quintiles).

The Study of Health in Polynesia 4057 looked at adults between the ages of 20 and 79 (4). Low levels of IGF-1 were associated with a roughly 92% higher risk of mortality, but this association was only observed in men and no benefits were observed in women nor in men with highest IGF-1 levels.

Among 642 adults between 50 and 89 year old participating in the Fredrikberg Heart Failure Study it was observed that those with the highest IGF-1 levels had a 52% higher risk of death (5). Those with the lowest levels had lower mortality than those with the highest IGF-1, but higher than those with levels the two extremes.

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The DETECT study was the largest study of the bunch, looking at 6066 men and women between the ages of 18 and 95 (6). Those with IGF-1 levels either below or above average (the lowest and highest 10%) both had a greater risk of death. Further analysis revealed a U-shaped mortality curve with IGF-1 levels. These results were observed in women, but the results were not statistically significant.

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Thus it appears my initial suggestion that growth hormone has both positive and negative effects was correct. In further posts I’ll examine the association between GH/IGF-1 level variations on specific types of mortality, the influence of biochemically subtle GH/IGF-1 related gene mutations on health, theorize about why gender seems to play a role, and finally, propose what all this means with respect to certain elements of diet and nutrition.

References:

1. Roubenoff R, Parise H, Payette HA, Abad LW, D’Agostino R, Jacques PF, Wilson PW, Dinarello CA, Harris TB. Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study. Am J Med. 2003 Oct 15;115(6):429-35.

2. Laughlin GA, Barrett-Connor E, Criqui MH, Kritz-Silverstein D. The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo Study. J Clin Endocrinol Metab. 2004 Jan;89(1):114-20.

3. Kaplan RC, McGinn AP, Pollak MN, Kuller L, Strickler HD, Rohan TE, Xue X, Kritchevsky SB, Newman AB, Psaty BM. Total insulinlike growth factor 1 and insulin-like growth factor binding protein levels, functional status, and mortality in older adults. J Am Geriatr Soc. 2008 Apr;56(4):652-60.

4. Friedrich N, Haring R, Nauck M, Lüdemann J, Rosskopf D, Spilcke-Liss E, Felix SB, Dörr M, Brabant G, Völzke H, Wallaschofski H. Mortality and serum insulin-like growth factor (IGF)-I and IGF binding protein 3 concentrations. J Clin Endocrinol Metab. 2009 May;94(5):1732-9. doi: 10.1210/jc.2008-2138. Epub 2009 Feb 17.

5. Andreassen M, Raymond I, Kistorp C, Hildebrandt P, Faber J, Kristensen LØ. IGF1 as predictor of all cause mortality and cardiovascular disease in an elderly population. Eur J Endocrinol. 2009 Jan;160(1):25-31.

6. Friedrich N, Schneider H, Dörr M, Nauck M, Völzke H, Klotsche J, Sievers C, Pittrow D, Böhler S, Lehnert H, Pieper L, Wittchen HU, Wallaschofski H, Stalla GK. All-cause mortality and serum insulin-like growth factor I in primary care patients. Growth Horm IGF Res. 2011 Apr;21(2):102-6.

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