References to published papers, reports, etc.

Little is known regarding the long-term effects of caloric restriction (CR) on the risk for atherosclerosis. We evaluated the effect of CR on risk factors for atherosclerosis in individuals who are restricting food intake to slow aging. We studied 18 individuals who had been on CR for an average of 6 years and 18 age-matched healthy individuals on typical American diets. We measured serum lipids and lipoproteins, fasting plasma glucose and insulin, blood pressure (BP), high-sensitivity C-reactive protein (CRP), platelet-derived growth factor AB (PDGF-AB), body composition, and carotid artery intima-media thickness (IMT). The CR group were leaner than the comparison group (body mass index, 19.6 +/- 1.9 vs. 25.9 +/- 3.2 kg/m(2); percent body fat, 8.7 +/- 7% vs. 24 +/- 8%). Serum total cholesterol (Tchol), low-density lipoprotein cholesterol, ratio of Tchol to high-density lipoprotein cholesterol (HDL-C), triglycerides, fasting glucose, fasting insulin, CRP, PDFG-AB, and systolic and diastolic BP were all markedly lower, whereas HDL-C was higher, in the CR than in the American diet group. Medical records indicated that the CR group had serum lipid-lipoprotein and BP levels in the usual range for individuals on typical American diets, and similar to those of the comparison group, before they began CR. Carotid artery IMT was approximately 40% less in the CR group than in the comparison group. Based on a range of risk factors, it appears that long-term CR has a powerful protective effect against atherosclerosis. This interpretation is supported by the finding of a low carotid artery IMT.

Fontana L, Meyer TE, Klein S, Holloszy JO. Proc Natl Acad Sci U S A. 2004 Apr 19 (Epub ahead of print)"Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans".

A long-standing challenge to evolutionary theory has been whether it can explain the origin of complex organismal features. We examined this issue using digital organisms—computer programs that self-replicate, mutate, compete and evolve. Populations of digital organisms often evolved the ability to perform complex logic functions requiring the coordinated execution of many genomic instructions. Complex functions evolved by building on simpler functions that had evolved earlier, provided that these were also selectively favoured. However, no particular intermediate stage was essential for evolving complex functions. The first genotypes able to perform complex functions differed from their non-performing parents by only one or two mutations, but differed from the ancestor by many mutations that were also crucial to the new functions. In some cases, mutations that were deleterious when they appeared served as stepping-stones in the evolution of complex features. These findings show how complex functions can originate by random mutation and natural selection.

Lenski, R. E., C. Ofria, R. T. Pennock, and C. Adami. 2003. The evolutionary origin of complex features. Nature 423:139-144.

Brief discussion of the complete technical problem of cryonics, including application after cardiac arrest, and the high quality of brain preservation now achievable with vitrification.

Lemler J, Harris SB, Platt C, Huffman T, in: Annals of the New York Academy of Sciences, (2004, in press), "The Arrest of Biological Time as a Bridge to Engineered Negligible Senescence".

First detailed discussion of the application of nanotechnology to reverse human cryopreservation.

Merkle RC, in: Medical Hypotheses (1992, vol. 39), "The technical feasibility of cryonics", pg. 6-16.

Paper showing that dogs can be recovered after three hours of total circulatory arrest ("clinical death") at 0°C (32°F). This supports the reversibility of the hypothermic phase of cryonics.

Haneda K, Thomas R, Sands MP, Breazeale DG, Dillard DH, in: Cryobiology (1986, vol. 23), "Whole body protection during three hours of total circulatory arrest: an experimental study", pg. 483-494.

First paper showing that large organs can be cryopreserved without structural damage from ice.

Fahy GM, MacFarlane DR, Angell CA, Meryman HT, in: Cryobiology (1984, vol. 21), "Vitrification as an approach to cryopreservation", pg. 407-426.

First paper suggesting that nanotechnology could reverse freezing injury.

Drexler KE, in: Proceedings of the National Academy of Sciences (1981, vol. 78), "Molecular engineering: An approach to the development of general capabilities for molecular manipulation", pg. 5275-5278.

Follow-up paper showing partial recovery of brain electrical activity after 7 years of frozen storage.

Suda I, Kito K, Adachi C, in: Brain Research (1974, vol. 70), "Bioelectric discharges of isolated cat brain after revival from years of frozen storage", pg. 527-531.

First paper showing recovery of a mammalian organ after cooling to -196°C (liquid nitrogen temperature) and subsequent transplantation.

Hamilton R, Holst HI, Lehr HB, in: Journal of Surgical Research (1973, vol 14), "Successful preservation of canine small intestine by freezing", pg. 313-318.

First paper to propose cryonics by neuropreservation.

Martin G, in: Perspectives in Biology and Medicine (1971, vol. 14), "Brief proposal on (life extension): an interim solution", pg. 339.

Paper showing recovery of brain electrical activity after freezing to -20°C.

Suda I, Kito K, Adachi C, in: Nature (1966, vol. 212), "Viability of long term frozen cat brain in vitro", 268-270.