Some Papers on IGF-1 And Insulin in Aging
Mainstream research on the biochemistry of aging and longevity - with an eye to slowing down aging rather than repairing it - is at this time primarily focused on a small number of areas. One is the cluster of mechanisms and signaling pathways associated with insulin and insulin-like growth factor 1 (IGF-1). You might recall that a tenfold increase in nematode life span was engineered via manipulation of IGF-1, for example:
Reis' team discovered that a mutant in the insulin/ IGF-1 pathway of C. elegans slows development but ultimately produces adults he described as "super survivors," able to resist levels of toxic chemicals that would kill an ordinary worm. Although the adult lifespan of C. elegans is normally only two to three weeks, half of the mutant worms were still alive after six months, with some surviving to nine months.
While perusing PubMed, I noticed a couple of papers on insulin, IGF-1, and aging:
In invertebrates, signaling pathways homologous to mammalian insulin and insulin-like growth factor (IGF-1) signal transduction have a major role in the control of longevity. There are numerous indications that these pathways also influence aging in mammals, but separating the role of insulin from the effects of IGF-1 and growth hormone (GH) is difficult.
In mice, selective disruption of the insulin receptor in the adipose tissue extends longevity. Increases in lifespan were also reported in mice with deletion of insulin receptor substrate 1 (IRS1) in whole body or IRS2 only in the brain. GH deficiency or resistance in mutant mice leads to hypoinsulinemia and enhanced insulin sensitivity along with remarkably extended longevity.
These characteristics resemble animals subjected to calorie restriction. Studies of physiological characteristics and polymorphisms of insulin-related genes in exceptionally long-lived people suggest a role of insulin signaling in the control of human aging.
Role of the GH/IGF-1 axis in lifespan and healthspan: Lessons from animal models
Consistently, two interventions, caloric restriction and repression of the growth hormone (GH)/insulin-like growth factor-1/insulin axis, have been shown to increase lifespan in both invertebrates and vertebrate animal model systems. Caloric restriction (CR) is a nutrition intervention that robustly extends lifespan whether it is started early or later in life. Likewise, genes involved in the GH/IGF-1 signaling pathways can lengthen lifespan in vertebrates and invertebrates, implying evolutionary conservation of the molecular mechanisms.
Specifically, insulin and insulin-like growth factor-1 (IGF-1)-like signaling and its downstream intracellular signaling molecules have been shown to be associated with lifespan in fruit flies and nematodes. More recently, mammalian models with reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have extended lifespans as compared to control siblings. Importantly, this research has also shown that these genetic alterations can keep the animals healthy and disease-free for longer periods and can alleviate specific age-related pathologies similar to what is observed for CR individuals. Thus, these mutations may not only extend lifespan but may also improve healthspan, the general health and quality of life of an organism as it ages.
With the level of interest presently devoted to this subject, I imagine that a decade from now researchers will fully understand how IGF-1, insulin, growth hormone, and calorie restriction all fit together into the bigger picture of the natural range of metabolic processes in response to circumstances. Your diet and exercise choices change the way your biochemistry operates: the biochemical mechanisms by which this happens have a deep evolutionary history.
It seems evident that some large portion of the research community will continue to forge ahead with strategies to shift your metabolism into a better state for your long term health - replicating calorie restriction, or mutations known to be beneficial. This is not a path to radical extension of the healthy human life span, however. It will only produce modest gains. To move beyond the small goals, we have to aim to repair the damage of aging rather than just slow down its accumulation. It will be no harder to achieve from where we are now, and the rewards are far greater.
Creatine boosts IGF-1 during/after exercise, creatine also support longevity(more or less). This seems a bit of a paradox with the findings in the article. I'm I oversimplifying things? Or mixing 2 different this?
It's just that in my reginme I'm boosting IGF-1, I'm wondering if this is pro-aging
I think it's far too early to conclude that IGF-1 pathways or effected genes in humans are totally analogous to that in mouse models. For example - your last posting:
More On CR Differences Between Species (October 23 2008)
As Ouroboros notes, researchers are beginning to uncover differences in the mechanisms of calorie restriction (CR) between species. This lends support to the evolutionary arguments that CR, while demonstrated to be very good for human health, isn't going to extend maximum human life span to the same degree it does in mice. "Decreased IGF-1 levels are associated with increased lifespan. Calorie restriction is also associated with increased lifespan. In rodents, CR is associated with decreased IGF-1 levels, leading to the (still unproven) hypothesis that the effects of CR are mediated by modulation of the IGF-1 axis. In humans, however, the situation is slightly different: As in rodents, the human IGF-1 pathway contains several genes that appear to regulate longevity. The longevity benefits of CR are still under study, but it does appear that certain types of fasting regimens have protective effects against e.g. tumor growth. According to this new study, however, CR has no effect on the levels of functional, circulating IGF-1 [in humans] - so while IGF-1 may regulate longevity and CR may protect against cancer and other age-related maladies, it doesn't appear that CR mediates its effects via IGF-1."
It seems like whatever makes you grow or speeds up transcription of DNA creates more errors - or a smaller window of opportunity for repair processes to take place.