extropians: Re: mind control happened

If I read the following correctly, it seems to indicate that gross = oxidative stress (free radical damage?) leads to 5 1/2 times the rate of = telomeric shortening than normal cell doubling would. If true, doesn't = this suggest a direct causal connection between the free radical theory = of aging, and the telomeric/proliferative senesence apoptosis model? I = had been thinking that the rate of telomeric shortening was a constant, = and that the NUMBER of doublings was the only thing which invoked the = Hayflick limit. Now, if I interpret the below correctly, there is a = quintuple whammy when cell doubling occurs under free radical oxidative = stress such as in crush injuries etc. Am I getting this right?

Mild hyperoxia shortens telomeres and inhibits proliferation of = fibroblasts: a model for senescence?

von Zglinicki T, Saretzki G, Docke W, Lotze C Institute of Pathology, Humboldt University, Berlin, Germany.=20

Mild oxidative stress as exerted by culture of human WI-38 fibroblasts = under 40% oxygen partial pressure blocks proliferation irreversibly = after one to three population doublings. Hyperoxically blocked cells are = similar to senescent ones in terms of general morphology and lipofuscin = accumulation. Moreover, they, like senescent fibroblasts, are blocked = preferentially in G1 as evident from DNA content measurements by flow = cytometry. Southern blotting of AluI- and HinfI-restricted genomic DNA = shows an increase of the rate of telomere shortening from 90 bp per = population doubling under normoxia to more than 500 bp per population = doubling under hyperoxia. In every case, proliferation is blocked if a = telomere cutoff length of about 4 kb is arrived at. The fact that = telomere length correlates with the final inhibition of proliferation = under conditions of varied oxidative stress, while the population = doubling level does not, suggests that telomere shortening provides the = signal for cell cycle exit in senescence. In postmitotic cells, no = further telomere shortening occurs. However, the sensitivity of terminal = restriction fragments to S1 nuclease increases, indicating the = accumulation of single-strand breaks in telomeres of nondividing = fibroblasts. This effect is found both under normoxic and hyperoxic = culture, although it is more pronounced under conditions of higher = oxidative stress. It might be speculated that accumulation of = single-strand breaks and the resultant loss of distal single-stranded = fragments during replication could be a major cause of telomere = shortening, possibly more important than incomplete replication per se

If I read the following correctly, it seems to = indicate that=20 gross oxidative stress (free radical damage?) leads to 5 1/2 times the = rate of=20 telomeric shortening than normal cell doubling would. If true, doesn't = this=20 suggest a direct causal connection between the free radical theory of = aging, and=20 the telomeric/proliferative senesence apoptosis model? I had been = thinking that=20 the rate of telomeric shortening was a constant, and that the NUMBER of=20 doublings was the only thing which invoked the Hayflick limit. Now, if I = interpret the below correctly, there is a quintuple whammy when cell = doubling=20 occurs under free radical oxidative stress such as in crush injuries = etc. Am I=20 getting this right?

Mild oxidative stress as exerted by culture of human WI-38 = fibroblasts=20 under 40% oxygen partial pressure blocks proliferation irreversibly = after one to=20 three population doublings. Hyperoxically blocked cells are similar to = senescent=20 ones in terms of general morphology and lipofuscin accumulation. = Moreover, they,=20 like senescent fibroblasts, are blocked preferentially in G1 as evident = from DNA=20 content measurements by flow cytometry. Southern blotting = of=20 AluI- and HinfI-restricted genomic DNA shows an increase of the rate of = telomere=20 shortening from 90 bp per population doubling under normoxia to more = than 500 bp=20 per population doubling under hyperoxia. In every case, proliferation is = blocked=20 if a telomere cutoff length of about 4 kb is arrived at. = The=20 fact that telomere length correlates with the final inhibition of = proliferation=20 under conditions of varied oxidative stress, while the population = doubling level=20 does not, suggests that telomere shortening provides the signal for cell = cycle=20 exit in senescence. In postmitotic cells, no further telomere shortening = occurs.=20 However, the sensitivity of terminal restriction fragments to S1 = nuclease=20 increases, indicating the accumulation of single-strand breaks in = telomeres of=20 nondividing fibroblasts. This effect is found both under normoxic and = hyperoxic=20 culture, although it is more pronounced under conditions of higher = oxidative=20 stress. It might be speculated that accumulation of single-strand breaks = and the=20 resultant loss of distal single-stranded fragments during replication = could be a=20 major cause of telomere shortening, possibly more important than = incomplete=20 replication per se