1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
|
This is Greg saying why Aubrey is too pessimistic about longevity. Aubrey is often critized. Aubrey is too pessimistic. I'm here representing Interbean Biomodical today. Intervene Biomedical. I'm trying to figure this out. Is this the pointer? Yes. Um. What I'm going to tell you about today is taken from the chapter in the book "Future of Aging" coming out in March of next year. There's human aging; different methods. Aubrey has a chapter in the book.
What I disagree with Aubrey is that in many ways, aging is not primarily damaging, but it's actually biological choice. The result of gene expression that is inappropriate. He's right about the pointer not working. There's an aging phenotype. I'm sorry if I go a little technical in this talk, even if you're not a biologist. The reason this exists is that it has to do with reproduction. So if aging is a choice, we can make a different choice, and block the expression of the genes that lead to the aging phenotype. This is an example of why this is true.
Chooses aging in C. elegans. This is the lifespan of normal c. elegans. The mean life span is 10 days, and if you knock out one gene. This is how long they live. They live 10 times longer. None of them are dead at an age at which all of the control worms are dead. Aging is a choice. This is a fact as far as I'm concerned. This is a major system for effecting this choice. Why should life be set up this way? I can't explain it, I just recognize it. If we're going to try to explain it, unbrittled reproduction in the wild could lead to overpopulation, niche exhaustion and so on; with aging you can try out gene mixing and have a longer chance of surviving. Whether this is true or not is unknown.
Aging does not happen under a large number of different conditions. In many species, there is no aging before sexual maturation. The c. elegans has a mean life span of 10 days. We can push it up to 70 days by prolonging the time that the worm stays in the premature stage. You can keep it in the pre-mature stage for 6x longer than the normal lifespan. This horizontal life span is actually the adult life span, it's not shortened regardless of how long they spend in the juvenile span. Later, it would effect reproductive ability. You get an absolute one to one relationship. The longer you spend in your entire life. This is not just for worms, it's also in marine molluscs. Larval period can be extended, and then you add in 21 days to the mean life span. No problem with the 2nd generation life span either. There's no damage accumulated over the period of time that is the normal mean life span. Aging is chosen at the age of maturation. Life chooses to not age beings before they choose to exist. These are Carrion beetles. You can make them live 2 weeks longer. If you intercept them when they are juveniles, you completely withdraw food. Their size diminishes. They reverse their aging process. They go to immature larval stages. If you let them eat for a while, for 4 weeks, they regrow, and the development proceeds in the normal direction, and you can repeat this over and over again. They never do age.
How are these choices mediated? In higher organisms they are connected to methods related to reproduction. In salmon, if you castrate salmon they live longer. With normal salmon, if you remove the testes from male salmon, you find that a few of them do not regenerate the testes. And those few animals remain juvenile. Their maximum lifespan is extended by 60%. Octopus situation is even more dramatic. A female octopus will die like clockwork after 10 days after she hatches her eggs. There are two endocrine glands in the octopus, the "optic glands", if you remove one of them. The female lives 40 days after egg hatching. And 140 days if you remove both of them, which is 14x the normal life span. We're interrupting aging. This happens in worms as well. This is the normal life span of c. elegans, this is one of the longevity mutations that I showed before. On top of this mutation, you use a laser beam to wipe out the gonads. They live 6x longer. Only the germline cells are responsible for this effect. You still have lifespan extension. You're getting rid of this machine because of germline cells. Now, it's not just for animals. This works in humans as well. If you're a mental patient in an asylum, with a 65 year mean life span. That would pertain well to this crowd. Gonad-driven aging in humans. If you're male and they remove your testicles at age 12, you will live about 11 years longer. If they delay this process, you will live longer, but not as much. There's another piece of evidence. The normal human male is sentenced to death early because of something on the Y chromosome. This is a group of Amish families that have a pedigree tracing back a few generations. The females were not effected by this, they didn't have Y chromosomes. The males with the deletion would live 12 years longer than the males that didn't have the deletion.
What other evidence is there for programmed aging? CoQ10 is needed for aging. Most tissues, as you're older if you're a mouse, there's a bit of a dip in some types of muscles. In the heart, there's a 2/3rds decline and CoQ10 synthesis, shortly before the age before you find half the animals dead; you find it spiking. According to George Webster, he looked at global rates of protein synthesis as a function of age in many tissues, he found that protein synthesis crashes between 20 to 21 months. The mRNA, the nuclear signal, which you need to make proteins globally, falls dramatically, right about around global synthesis falls. This is a programmed aging change. It shuts off protein synthesis. And protein synthesis is ind of important. Her'es another thing that is important. Bruce Aimes was the first to show the accumulation of DNA damage accumulation with aging. There's a 6-fold drop in repair in DNA damage. The drop is much more powerful than the increase in damage. Once again this is a choice, this is biologically controlled either by intent or not. Same thing happens with DNA. Developmentally, there's this massive drop-off. These are in animals that are really quite young. This precedes the results of DNA damage/delete in mitochondria that essentially involve apoptosis. Apoptosis is programmed cell death. Okay.
Here's the way I see human aging. And aging in general. And why the deck is stacked against us. And how we have to intervene to do something about it. The game of life is to be hatched or be born and produce germline cells, and reproduce, we have to do that or else the species goes extinct. Insulin, insulin-like growth factor 1, you can't do that unless you eat. You can't do much with calories unless you have insulin. Eating shuts down your DNA repair. Shuts down anti-oxidants and stress resistance, as do these hormones. You can't survive without them, and you can't survive with them. You need growth hormone to grow and maintain the muscles in your organs. We told into little old men and women. Our internal organs atrophy. This is not a good thing. In order to prevent that, we would have to incure a lot of DNA damage and so forth. The game is stacked against us. There is no way to escape from this under natural conditions. The germline, in one way or another, produce aging in of itself. There's more, because maturing leaves to 3 gratuitous changes that happen that are not needed at all; one wipes out your immune system. Another one is adrenal involution, it's the death of cells selectively in your adrenal gland; and there's another one that causes an over-reduction in growth hormone. And you need that.
Making a different choice. There are people that do on some level. Here's your immune system function if you're a normal person. If you have lower than normal thyroid hormone levels; if you have hyperthyroid, you can have normal immune system function up to the age of 90. Thymic involution is where your thymus shrinks. Here's an older thymus with growth hormone. It grows back. A thymus plus zinc can grow it back in a mouse. This is your old thymus, plus a male contraceptive, growing back the thymus in a rat model. And this is a human CT scan showing no thymus before growth hormone, and growing it back after growth hormone treatment. You can reverse an 80% reduction.. as long as you're at 80% less.. mean life span. If we can get rid of immune system aging, we can do a lot of other neat things. Your ability to synthesize DNA in response to drug stimulation goes way down if you're a mice. A thymus transplant brings that back. Your thyroid levels go down, but those are corrected as well. Your brain beta receptors go down. That's corrected as well, but I don't know why. You become pre-diabetic, and insulin goes up; that's corrected too. The liver cells have 2x DNA as they should, and this is corrected by a thymus transplant for some reason. There are master switches. What about adrenal involution? This is an experiment that I did that shows if you take a drug that allows you to make your own DHA, your exercise can be improved. Your lean body mass goes down with aging, your fat mass goes up, your organs are withering and atrophying. If you give growth hormone all of that is reversed. CoQ10 goes down close to death. If you give it to animals they look more energetic and their maximum life span is extended. Not making RNA, not making protein? You can reverse the effects of loss of transcription, and in muscle, growth hormone increases protein synthesis. If you get acetlycarnitine, your ability tyo transfer cyt c is corrected.
No need to re-engineer mitochondria. I only have 2 minutes here. 97-year-old fiberglass mitochondria show an 80% drop in protein synthesis. Acetlycarnitine will reverse this as well. If you restore the turn over in the cell. If you look at all liver cells with an electron microscope, you see they become normal as well. There are systems in the body that export lipofuscin in the cell. You find it in many different species. This is stimulated by.. which reverses lipofuscin accumulation throughout the brain. It's also removed by many other agents. In terms of mammals, this is a single change mutation. The females only begin to die at the age at which the control animals are dead. In humans you see much the same thing. Aging seems to stop at which you hit 110. And it seems to imply that aging is a choice. One last slide. We've talked about the relationship life and sex, it's not really true that living longer means no sex. The mole rate turns this upside down. The breeders and non-breeders: the breeders live 2x long.
Let's make another choice. Block the genes that cause aging. Rev-up the genes that cause an anti-aging phenotype. Contact me at greg@intervenebio.com or intervene@sbcglobal.com
|
