"Mortality of an organism is clearly associated with terminal specialisation in sexual reproduction."
And:
"Destructive effects of stochastic events are visible only when allowed by the specific life program of an organism."
So it's both, but some of the stochastic events are better prevented by the asexual programs. Or it may be more correct to say that sexual programs work better when destruction is deliberately permitted. Eventually you do get hit by some sort of bus, though—whether that be an actual bus or a retrovirus that messes up your program. Much later in the program, all it takes is pneumonia. Stochastic events act as part-of/input-to a genetic algorithm to select for a better program when you get to step #3 and create a new program via sexual reproduction and genetic recombination. We're all the program. Duh.
I'm really not sure why people argue over whether death is programmed. Life in general is programmed, centered about sexuality, reproduction, and child rearing for the next stochastic experiment (said: "baby:")
- You're born.
- You hit puberty (menses or lots more muscle/hair/deeper voice).
- You reproduce.
- You hit menopause ("F" program only).
- You help raise grandkids (more recent to the species).
- You die.
The male program is slightly more flexible—lacking step #4—probably because women having babies too late is provably really bad for the species, so that's programmed to stop. Whether menopause is "strongly" caused by stochastic events or actually programmed to happen after N days is an interesting question.
This is the same program in every human population. #1 obviously never occurs after #2 or #3. But #4 always happens around the same time in women according to a program of gene expression. I really wonder why people doubt this sometimes.
If you don't buy this theory, ya'll are trying to beat #6 without noticing it's always steps #1-5 in that order prior to #6. In a computer program it would look like this:
Human logjam = new Human(T_MALE);
logjam->puberty();
logjam->bowchikabowwow();
logjam->playwithgrandkids();
delete logjam;
Now in real life it's much more complicated and not declarative like that. According to that paper, stochastic events make it look random. Instead it looks more like:
Human logjam = new Human(T_MALE);
logjam->puberty();
logjam->bowchikabowwow();
logjam->stochastic->decline(TD_PHYSICAL);
logjam->playwithgrandkids();
logjam->stochastic->decline(TD_PHYSICAL);
logjam->stochastic->decline(TD_MENTAL);
Then it takes an increasingly small insult to wipe me out after each ->decline(). The ->decline() in lieu of actual declaratives is what makes it all look random, but it really probably isn't at all. It takes a smaller and smaller "stochastic bus" until it's "just" pneumonia, and then you die. Pneumonia was always in your nostrils, but stochastic->decline didn't do enough to let the pneumonia bus through.
To make it even more confusing, all the systems are connected through feedback loops and the train eventually leaves the station on your death. The fact that you're metabolically alive is powering several feedback loops—esp. endocrine—that are killing you with the same ATP you need to stay alive.
That kind of unifies why caloric restriction can work (fewer stochastic events and a slower clock), but only does so much. Entropy and stochastic events happen no matter what. They're part of the (input to the) program. Things like RAGE receptors may have a purpose—to help us get hit by a bus. Sometimes I have no better explanation. You can argue that all of these mechanisms are to help a sick cell die, and sometimes that's true. Some mechanisms are less convincingly so.
Telomeres may be a clock and a stopgap anti-cancer heuristic and very high upper bound on program length. There is clearly statefulness in our program—and more than just general ordering—some steps never occur before other steps. I don't believe you can achieve a sequence like that without a clock. Telomeres may be one of those:
We demonstrate that chromosome looping brings the telomere close to genes up to 10 Mb away from the telomere when telomeres are long and that the same loci become separated when telomeres are short. Furthermore, expression array analysis reveals that many loci, including noncoding RNAs, may be regulated by telomere length.
It's also completely possible that the "metabolic memory" perpetuated by AGEs are one of many parts of a clocking mechanism, but they can't enforce program execution order nearly as well as a clock like (perhaps) a telomere—that's much too random. The fact that a telomere looks sort of like the original programs like these: https://en.wikipedia...ki/Punched_tape shouldn't be lost on anyone in computer science. They'd be functioning more like a complicated register that almost-monotonically decreases, but it's difficult for me not to see this analogy.
I do doubt making a telomere longer would directly cause cancer because telomere dysfunction is only 1 of hundreds of subsystems in human physiology that cause senescence — like p53, for example. Telomere dysfunction itself causes termination via p53! It's just an additional checkpoint to stop unnecessary replication (an upper bound in addition to everything else) in the event that a cancerous program materializes. So longer telomeres might enable a few thousand more cell cycles but also yield gene expression that stops it more effectively if you believe that.
If cells replicated full time you'd be gray goo. Telomere dysfunction only stops the bad programs that try to turn you into gray goo. The idea that simply lengthening them somewhat through some sort of transient mechanism will cause cancer is far-fetched. On the other hand, disallowing telomerase to be expressed chronically will kill lots of cancers because they'll need to lengthen telomeres to keep creating gray goo. That's what Geron is actually working on doing after giving up on cycloastragenol awhile ago.
Wow, you're all over the place. So disorganized.
AGE accumulation is [...] unavoidable! ROS generation is also not random... it's a consequence of our human chemical constitution.
really? a consequence of our human chemical constitution? 
Well, thanks! That explains it all.
Furthermore, do a little research on AGE accumulation and its effects on normal tissue function......... i.e. stem cell activity, maintenance/healing. AGE accumulation leads to the aging phenotype.
As for negligible senescent animals..... Do you think the biochemistry of a lobster or rockfish is comparable to a mouse or a human?
Oh! so you're saying that AGEs is actually responsible for aging?! Explain please why does not it accumulate in animals with negligible senescence.
And if you don't like lobster or rockfish, take an albatross, a whale, or a turtle.
Better yet, explain why a lab mouse and a naked mole-rat have such vastly different lifespans. According to you, due to their very similar ratty "chemical constitutions" they should have the same levels of AGEs and ROS in the same timeframe. Why don't they?
So it's both. Random. By design. Both.
Well, it depends. There was a good article posted recently on this very topic. You guys should read it. It discussed a wide variation in how different animals age, if at all. Exactly this wide difference in aging phenotypes among various species proves that aging is controlled genetically. Think about it. If it were otherwise, everyone would age at about the same rate, depending on their metabolic rate and exposure to environmental stresses. And, while overall, various species of about the same size would have about the same lifespans, at the same time, there would be a wide variation in natural lifespan among individuals of the same species (depending on their individual "rate of living"). Instead, an aging species lifespan is tightly controlled genetically. But read for yourselves: Principles of alternative gerontology, 2016
Edited by Logjam, 02 May 2016 - 12:27 AM.
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