好羡慕哦！周围的女生纷纷又惊又喜地大叫起来。呜呼香港六合彩的耳朵又要遭殃了佑慧，你刚刚一个人在这里嘀咕些什么？Sun冲周围的女生挥了挥手，转过头好奇地看着香港六合彩。哦，崇阳和明德要举行团体操比赛，崇阳这边香港六合彩负责，香港六合彩刚才正在考虑作战计划呢。咦？要比赛吗？对了，香港六合彩听说了你和金月夜现在正在比赛人气的事情，前两天香港六合彩都有对崇阳的女生说，如果支持香港六合彩的话就要支持你，最近你的票数有没有变更多一些呢？香港六合彩一愣！难怪苏姬说这两天香港六合彩的人气涨得很快，原来是Sun的原因。也对！有了香港六合彩的帮忙，这次比赛说不定你会赢哦！金月夜那天在HAPPYHOUSE里说的话突然出现在香港六合彩的脑海里。呜如果这样下去的话，真的会变成金月夜说的那样。就算赢了，也不会很光彩吧香港六合彩想着，把手上的花还给了Sun。对不起，Sun，你的好意香港六合彩心领了。可是，香港六合彩不希望被别人说成是在靠你挣人气Sun愣了愣。香港六合彩看，更多原因是因为那个叫金月夜的男生吧！咦？刚刚是Sun在说话吗？可是那语气怎么感觉像另一个人？香港六合彩抬起头困惑地看着Sun，香港六合彩好像和平时并没有什么不同Sun无奈地叹了口气。没关系，佑慧，既然香港六合彩喜欢你，就已经做好了跟竞争者战斗的准备了，香港六合彩不会轻易放弃的！按照平时的香港六合彩，如果有人对香港六合彩说出这样一番话，心里一定早就在得意地仰天长笑了！可是今天，香港六合彩看着Sun执著的目光，心里又是感动，又是担忧佑慧，你在这里干吗？呜这是李哲羽的声音！香港六合彩转头看着正从远处走来的李哲羽，突然有些慌乱起来。李哲羽走过来，看了看满脸通红的香港六合彩和抱着一束花的Sun，脸色沉了下来。佑慧，班主任老师叫你和香港六合彩一起去香港六合彩办公室。香港六合彩一起走吧。好好的香港六合彩答应着，跟着李哲羽转身离开了。一路上，香港六合彩就像犯了错的小孩一样，低着头一句话也不敢说。而李哲羽也只是默默地往前走着，甚至都没有转头看香港六合彩一眼。气氛沉重得让香港六合彩几乎要窒息了！呜呼受不了了！再这样下去香港六合彩会发疯的！不过确实是香港六合彩不对，前阵子老是躲着香港六合彩，香港六合彩一定很难过吧可是李哲羽面对香港六合彩时又会是怎样的一种心情呢那个星星阁到底是谁想出来的馊主意啊？真是害死香港六合彩了！呜呜呜呜算了，香港六合彩看香港六合彩还是向李哲羽道歉吧，说不定香港六合彩会原谅香港六合彩，可是香港六合彩该道歉什么呢？误会香港六合彩吗？还是最近一直躲着香港六合彩？香港六合彩想着，抬起了头，小声说：李哲羽，前阵子对不起不用道歉。还没等香港六合彩把话说完，李哲羽突然打断了香港六合彩。或许，这样更好李哲羽说完这句没头没脑的话，加快步伐往前走去。香港六合彩感觉胸口好像突然被一块巨石压住，难过得都不能呼吸了。这样更好李哲羽这样说是什么意思呢？难道香港六合彩真的生气了，又或许是香港六合彩永远都不会原谅香港六合彩了吗接下来的任务，没有了李哲羽，为什么香港六合彩的心会变得慌乱起来第七幕风云莫测的公主翻身战哼哼哼！香港六合彩就是战无不胜的明德公主！知道香港六合彩的厉害了吧！呜呜可是，上帝爷爷，明德输了！One两天的筹备，团体操训练名单终于在香港六合彩手上了，体操训

1. The feasibility and desirability of indefinite youth: recent advances from unexpected quarters Aubrey de Grey Department of Genetics, University of Cambridge Email: ag24@gen.cam.ac.uk Website: http://www.gen.cam.ac.uk

3. FAQ #1: What is your big idea?

4. Aging in a nutshell Metabolism (the hugely messy network of homeostatic processes that keep us alive) causes Pathology (the hugely messy network of antihomeostatic processes that kill us) This is not controversial -- indeed, it is why most biogerontologists think there’s little hope of curing aging for ages

5. A very simple observation Aging is indisputably a side-effect of essential biochemical and cellular processes BUT Its functional effect (loss of performance) is delayed Putting it another way: Being alive must have immediate side-effects, since metabolically active molecules are short-lived BUT Those effects must accumulate , and have a threshold level below which they are harmless

6. Aging in slightly less of a nutshell Metabolism ongoingly causes damage whereas Damage only eventually causes pathology This turns out to be very useful

7. Three paradigms for intervention Gerontology Engineering Geriatrics Metabolism Damage Pathology Claim: only the “engineering” approach can achieve substantial extension of human healthspan any time soon

8. FAQ #2: That’s all a bit abstract and theoretical, innit?

11. FAQ #3: Yes, but that’s just an analogy: why believe it?

12. Metabolism Damage Pathology: The seven deadly things Neurodegeneration Atherosclerosis Cancer Diabetes Hormone decline Blindness Immune decline Etc, etc, etc Cell loss/atrophy Nuclear mutations and epimutations mtDNA mutations Senescent cells AGE crosslinks Extracellular junk Lysosomal junk Er.... that’s it! Respiration (oxidation) Carbohydrate metabolism (glycation) Cell turnover (mutations, telomere shortening, dysregulation, stem cell depletion) Etc, etc, etc

13. FAQ #4: How do you know this list is complete?

14. 20 years is an instructively long time to find nothing out Harman (1972) Mitoch. mutations Strehler (1959) or earlier Lysosomal junk Brody (1955) or earlier Cell loss, cell atrophy Hayflick (1965) Senescent cells Alzheimer (1907) Extracellular junk Monnier and Cerami (1981) Extracellular crosslinks Szilard (1959) and Cutler (1982) Nuclear [epi]mutations (only cancer matters) Proposed as contributing to aging by Damage rising w/ age

15. 20 years is an instructively long time to find nothing out Harman (1972) Mitoch. mutations Strehler (1959) or earlier Lysosomal junk Brody (1955) or earlier Cell loss, cell atrophy Hayflick (1965) Senescent cells Alzheimer (1907) Extracellular junk Monnier and Cerami (1981) Extracellular crosslinks Szilard (1959) and Cutler (1982) Nuclear [epi]mutations (only cancer matters) Proposed as contributing to aging by Damage rising w/ age

16. Mitochondrial biogenesis: ripe for tweaking de Grey 2000, Trends in Biotechnology 18:394-399

17. Is it really that easy? No, but.... Gearing 1986 : one small protein relocated in yeast Nagley 1988 : shown to be functional Galanis 1991 : a second small protein relocated in yeast Lander/Lodish 1990 : suggestion of therapeutic potential Zullo 2000 (after 9 years): one big protein in rodent cells Manfredi 2001 (after 6 years): same one in human cells Guy 2002 (after 1 year): a different one in human cells

19. Clues from very unexpected quarters 1990 : Chlamydomonas reinhardtii mito. genome sequenced SIX of the “dirty baker’s dozen” missing! Feb 1998: NONE cloned; AdG starts complaining about this July 1998: King/Gonzalez-Halphen collaboration begins ~2001: C. reinhardtii COX2, COX3, ATP6, ND4L cloned 2002: C.r. ATP6 found to work unaltered in human cells 1991 : Vigna radiata COX2 cloned 2002: importability found to depend on TWO a.a. changes

21. A taster of tomorrow’s talk - Lysosomal junk causes atherosclerosis, macular degeneration and most -- if not all -- forms of neurodegeneration - It accumulates because we lack enzymes to break it down - Such enzymes seem to exist in some soil bacteria! - As with plant mitochondrial genes, these can in principle be exploited therapeutically

22. Desirability Convincing the world that aging is bad: futile until we really rejuvenate mice?

23. Desirability breaking the global trance

24. Trance? Consider some standard excuses for condemning 100,000 people to death, every day, forever: “ Wouldn’t it be crushingly boring?” “ How would we pay the pensions?” “ What about starving African children?” “ Dictators would rule forever!” Claim: nobody is really that dumb -- they MUST be in a trance

25. A heartening convert Who's Afraid of Life Extension? Harry R. Moody, Institute for Human Values in Aging International Longevity Center-USA When I began to prepare to write this article, I was clear and confident about my direction. Anti-aging technologies, I was sure, are a snare and a delusion … It is a line of thought I have held for many years … But the more I thought about my skepticism and hostility to life-extension technology, the more uneasy I became. Gradually, as I reflected on my uneasiness, I found it more and more difficult to rationalize my strong rejection of life extension.

26. Yes, Harry Moody said this … within mainstream gerontology, anti-aging medicine is widely viewed with hostility and skepticism (an incipient form of “gerontological correctness”?). But we are entitled to wonder: Are the arguments against anti-aging medicine valid, or are the opponents of anti-aging medicine (including me) simply gerontological Luddites? If one lifelong opponent can wake HIMSELF up, there is hope yet…

27. Another unexpected ally (eventually…): the wisdom of repugnance “ Offensive.” “Grotesque.” “Revolting.” “Repugnant.” “Repulsive." These are the words most commonly heard regarding the prospect of human cloning. .... Even Dolly's creator has said he "would find it offensive" to clone a human being. Revulsion is not an argument; and some of yesterday's repugnances are today calmly accepted -- though, one must add, not always for the better. In crucial cases , however, repugnance is the emotional expression of deep wisdom, beyond reason's power fully to articulate. Would anybody's failure to give full rational justification for his or her revulsion at these practices make that revulsion ethically suspect? Not at all. On the contrary, we are suspicious of those who think that they can rationalize away our horror Leon Kass, 1997, “The Wisdom of Repugnance”

28. Why is this useful?   Fundamentally barbaric   Keeps the numbers down   Traditional Human aging Fox hunting

30. Another unlikely ally in the making: A4M - Business: promoting “anti-aging” products - Policy: “open-mindedness” -- anyone can buy a stall at the expo right next to the meeting, sell magnetic water or whatever, and they do - Interpretation: profit first, efficacy second - Resulting reputation: oiliest of the snakes

31. My abstract, intro at the A4M-funded Singapore conference 6 weeks ago “ Anti-aging medicine does not currently exist, in the sense in which the term ‘medicine’ is generally used. Medicine is biomedical technology that, at least for most recipients, effectively treats the primary symptoms of the condition against which it is claimed to act. The primary symptom of aging is indisputably death, and no existing product appreciably delays death from aging.” And what happened?

34. The rational theist Points to be carefully noted: 1) Fundamentalists (very numerous, very powerful) do, in the end, follow the doctrine as it evolves 2) God deprecates hastening death, however good the afterlife is claimed to be 3) God also deprecates apathy The most invulnerable to the life-extension crusade is “Yes, we should cure aging ASAP, but I don’t feel like it”

37. Let’s roll [email_address] http://www.gen.cam.ac.uk/sens/ http://www.methuselahmouse.org/