Free Radical Theory of Aging: Increasing the Average Life Expectancy at Birth and the Maximum Life Span

Summary: The founder of the free radical theory of aging again summarising the results that back the theory, and theorising on what could help slow down this process.

Interestingness: 2

Paper by Denham Harman, MD, PhD, in the Journal of Anti-Aging Medicine, Volume 2, Issue 3, Fall 1999.

(((This is a rewrite of the paper two issues ago, summarised here: http://readingrejuvenationresearch.blogspot.com/2010/09/aging-minimizing-free-radical-damage.html, with better editing and slightly abridged (no cool graphs). It was more interesting the first time around, but this version is more polished.

This one puts more emphasis on substances that could slow down the aging process. There are a couple mentioned in this one that weren't mentioned in the first one, but nothing particularly intesting.
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Abstract follows:

Continued improvements in general living conditions—e.g., better nutrition, medical care, and housing—during the past two millennia have increased average life expectancies at birth from about 30 years in ancient Rome to almost 80 years in the developed countries with no change in the maximum life span. Current average life expectancies at birth will be increased little by further improvements. The rate of accumulation of damage inflicted on us by our inherent aging process limits average life expectancy at birth under optimal living conditions to around 85 years and the maximum life span to about 122 years. The inherent aging process is caused by chemical reactions that arise in the course of normal metabolism. Attempts to significantly increase average life expectancies at birth and the maximum life span in the future, unlike in the past, will require an understanding of aging. The free radical theory of aging postulates that this process is caused by free radical reactions, largely initiated by superoxide radicals arising from the mitochondria at an increasing rate with age. Some measures based on the free radical theory of aging may further increase the life span without interfering with the activities of normal life include: (a) caloric restriction, (b) compounds that decrease O2 access to "electron-rich areas" of the mitochondria, and (c) substances that help to minimize mitochondrial damage. The foregoing are discussed briefly along with the amelioration of damaging reactions in early life that predispose to life-shortening diseases. The feasibility of the measures suggested above needs to be evaluated. This task should be both interesting and rewarding.

Rest of volume 2, Issue 2

The rest of issue 2 of 1999 consists of:

Some book reviews:

• "Gray dawn: How the coming age wave will transform America and the world", by PG Peterson. Populist-sounding book warning that the US is getting old. Not reading it going by that review.
• "Living to 100: Lessons in living to your maximum potential at any age", by TT Perls, M Hutter Silver, JF Lauerman and M Hutter-Silver. Book about how life at 100 can still be good. Feel-good book? Not reading it going by that review.
• "Life without disease: The pursuit of medical utopia", by WB Schwartz. Using genes to predict and prevent disease. Sounds populist. Not reading it going by that review.
• "The causes of aging", by AP Wickens. Sounds like introduction to biology of aging. Maybe ok.
• "Super T: The complete guide to creating an effective, save, and natural testosterone enhancement program for men and women", by K Ullis, J Shackman, and G Ptacek. Guide on how to use testosterone as a supplement. Even though it sounds like marketing crap, it could be interesting.

The gerontology literature review:

• "The centenarians are coming", by CG Wagner, in The Futurist. Usual Futurist content. Sounds similar to the "Living to 100" book above.
• "Longevity: The ultimate gender gap", by HB Simon, in Scientific American. Reviewer didn't like it and mostly gave differing explanations and recommendations for the reasons of why men and women have different life expectancies. I don't like the alternative explanations offered.
• "Aging: A message from the gonads", by DL Riddle, in Nature. Burning bits of somatic gonadal tissue in some worms extended their lifespan by 60% compared to standard. Paper-suggested theoretical background: fecundity and longevity are inversely proportional, controlled by hormones. IGF-1 signals lots of food. Interesting. (Further below *).
  
• "Analysis of telomere lengths in cloned sheep", by PG Shiels, AJ Kind, KHS Campbell, D Waddington, I Wilmut, A Colman, and AE Schnieke, in Nature. Dolly, and two other cloned sheep, have 20% shorter telomeres than expected for their age. Theorised that telomere length not reset. Other people (that the reviewer contacted?) not convinced the result is not a fluke, or just experimental error (supposedly hard to distinguish telomeres 19kB long from ones 24 kB long)

The usual other sections: web watch, literature watch and calendar.

* On reading the article/letter, the description above is a bit wrong. The note is a theoretical justification for the gonad ablation result from another group. The 60% longevity expansion effect only happens when they get rid of the germline precursor cells (that generate sperm and eggs) and leave the gonad precursor cells alone, but not when they blast both sets. He interprets this as sperm shortening life and gonads extending it (I didn't get the teleological reasoning). There's more gene analysis ending with DAF-12 and DAF-16 upregulation extending lifespan, maybe through catalase upregulation, and DAF-2 shortening it by inhibiting DAF-16.

How Human Longevity and Species Survival Could Be Compatible with High Mutation Rates

Summary: Hypothesising that humans select against deadly mutations primarily at the zygote stage.

Interestingness: 4

Paper by Leonid A Gavrilov and Natalia S Gavrilova, in the Journal of Anti-Aging Medicine, Volume 2, Issue 2, Summer 1999.


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Another short note, this one on how come the human race still exists considering the large amount of mutations that occur during each generation. They quote a number from a different study claiming 1.6 new harmful mutations per person, per generation. Their suggested mechanism on how to select against deadly combinations is by being very sensitive at the zygote stage, so having the deaths happen early. Their evidence for this is that the time lag between marriage and first child is around 16-19 months, giving time for about 7-10 failures. Doesn't sound like impressive evidence to me, but the idea is appealing anyway. They don't offer a mechanism as far as I can see on how the zygote is made so sensitive to deadly mutations.

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Is Telomere Shortening Related to Progeria?

Summary: Telomere shortening probably doesn't cause Hutchinson-Gilford progeria

Interestingness: 6

Paper by W Ted Brown in the Journal of Anti-Aging Medicine, Volume 2, Issue 2, Summer 1999.


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This is a short note speculating on whether progeria is caused by telomere shortening. The author says unlikely. Hutchinson-Gilford progeria is a fucking rare disease (1 in 8 million) of the type that pop up through a dominant spontaneous DNA mutation. Progerias are diseases that look like accelerated aging. This one starts being noticeable in toddlers between one and two years old, then they start looking old very quickly, going bald and losing subcutaneous fat, and have an expected lifespan of 13 years. 80% of them die of heart attacks and congestive heart failure, but they don't seem to get cancer, cataracts, osteoporosis or Alzheimer's like regular old people.

Fibroblast cultures extracted from progeria patients have an almost normal lifespan, but one paper reported shorter telomeres in them. Studies from Werner's syndrome, a different progeria that hits during early adulthood, give mixed results for shorter telomeres, but maybe some indication of faster telomere shortening.

Mice with telomerase knocked out don't show too many problems and in one study, could reproduce for at least six generations. By the sixth generation, their telomeres were much shorter and there were a lot of chromosome fusions. Other studies on these telomerase knockouts showed slightly lower lifespan, lower wound healing capacity, and more cancer. From this, he says it seems unlikely that telomere shortening would cause progeria. From what I remember, though, mice have way longer telomeres than humans to begin with, which would hide the effect a bit, but he didn't discuss that

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Recovery of Circadian Body Temperature in Aged Persons

Summary: Some body temperature measurements of old people, with some rising

Interestingness: 1

Paper by Iwao Hirosawa, Susumu Iwamoto, Junko Yoneda, Yasuhiko Wada and Akio Koizumi in the Journal of Anti-Aging Medicine, Volume 2, Issue 2, Summer 1999.


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They measured the temperature of 10 old people that were put into aged care, mostly after having a stroke. They measured many times a day for about a year. In their analysis, they split the people into two groups, the first one, consisting of four people, in which their temperature went up after they entered the care place, and the other of the remaining six, whose temperature didn't go up. Their summary says that maybe the people in the first group were under caloric restriction prior to entering, which got fixed once entering, thus raising their temperature. From the weight numbers, they were probably all borderline CR anyway (40 kg for women, 43 for men, 1.40 and 1.49 metres. Small people). The graphs are not clear to me. It isn't clear either whether the rise in temperature for those four people was a good or bad thing.

There is some further analysis of seasonal changes split across time of day, but I don't understand what it showed
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Abstract follows:

The human diurnal body temperature rhythm does not differ significantly between aged and young subjects; the amplitude and mean level, however, decrease with age. In order to know whether the core body temperature of disabled elderly persons was influenced by environmental factors, we measured the tympanic temperature of nursing home patients. In 4 of 10 tested patients, there was a statistically significant upward shift of the core body temperature within 1 month of admission (P < 0.05). This restoration of body temperature was observed to occur without any relationship to the season of admission. The amplitude of circadian body temperature did not change. There were significant seasonal variations in the diurnal body temperature range between summer and winter, especially between 0900 and 1100 hours in 5 persons with, and without, an upward shift of body temperature. The persons who recovered their body temperatures were thought to have been had lower-than-normal-body temperature for age prior to admission. Body temperature recovery after admission may have been caused by an improvement in energy intake and nutritional balance.