1:22:43 – IGF-1 tradeoff. Dr. Patrick recalls a study performed on mice where growth hormone production was knocked out. In the study, the mice who produced less growth hormone also lived 50% longer. This is a very counter-intuitive result because we assume that growth hormone repairs muscle and would be good for longevity.
1:23:32 – People with polymorphisms in the IGF-1 receptor tend to live very long lives (92+). Dr. Patrick mentions that this may be due to the lower likelihood of cancer that comes from these polymorphisms.
1:29:05 – If you over express growth hormone in a mouse, it has been shown that the mouse’s lifespan will be cut in half. So this is the flip side of the study mentioned above.
1:32:55 – Joe brings up myostatin inhibitors. At this point they have discussed the tradeoffs associated with growth hormone and longevity. Yet the myostatin inhibitor examples presented make an interesting case because the subjects in these experiments and accidents tend to live longer (according to the information Joe presents) and have very large muscles.
1:43:30 – Studies on caloric restriction increasing lifespan. 27 year long study of monkeys where some subjects received 30% less food. The restricted monkeys, at near the end of their life, look significantly more healthy than their non-restricted counterparts. There are images pulled up during this section; the images are quite telling.
1:45:20 – Caloric restriction can change the expression in thousands of genes. It helps genes which are involved in protein degradation and synthesis and a number of other important pathways.
1:46:00 – Hormesis. One of the big theories regarding the effect of caloric restriction on lifespan is the concept of hormesis. When an organism feels a small amount of stress, that organism will change the expression of certain genes involved in stress to prepare for another possible moment of stress. It is a form of conditioning the body goes through. Dr. Patrick brings up polyphenols in plants which serve the same basic purpose in plants. Consumption of polyphenols is recommended by health experts. We are dealing with stress better when we are introduced to a small bit of it; exercise works on the same principle. Extrapolate this to 27 years and this could explain why some monkeys age very differently from others.
1:47:04 – Epigenetics. Things you do throughout our life can alter your genetic makeup and thus these altered genes get passed along to your offspring. The idea behind it is that there are markers present that ‘sit on top of’ genetic material – these are typically methyl groups or acetylation groups – which ‘turn genes on or off’. When genes are turned on they are known as expressed. Note, there is no change in the DNA, only a change in what is being expressed; this differs from a mutation which actually changes the sequence of DNA. Epigenetic markers are modulated, they determine what is active and what is not in the DNA; they are a result of our environment and we therefore have an influence on what we express on a genetic level.
1:48:30 – Swedish study on caloric restriction. Controlling for economic status, males ages 9-12 who were around during years of famine (caloric restriction) would produce offspring that lived 32 years longer. They were also a quarter less likely to get cardiovascular diseases and type II diabetes. Theories as to why this applies to boys ages 9-12 look to the fact that boys undergoing puberty are introduced to a bit of stress and the developing sperm will retain information from a conditioned individual so this may be passed along.
1:52:45 – Another study looked at the epigenetic effects of stimulating environments on mice with neural degenerative diseases. Mice offspring ended up having the same learning benefits without being exposed to the stimulating environment (as their parents were).