doug@feedme.UUCP (Doug Salot) (06/10/88)
In pondering good topics of conversation for dinner parties, I
suddenly realized that I don't know what that branch of science
is called in which aging and death are studied (I don't believe
gerontology is considered a research discipline). Could someone
enlighten me? (I'm sure many of you could, but I mean specifically
about the study of death.)
Before I run out and subscribe to Death Today or Popular Dying,
does anyone want to give a rundown of current theory on the
subject? What cellular organelles are depletable (assuming
suitable nutrients are available from the environment)? Have
the mechanisms which determine whether (or how) a cell becomes
specialized and stops dividing been elucidated?
Oh, and while I'm at it, what is the standard definition of human
death these days? Is it flatline for some time span? If so, what
area of the brain is being monitored? Are there estimates for the
amount of cellular damage as function of CNS (or CV) inactivity time?
Thanks for your indulgence.
--
Doug Salot || doug@feedme.UUCP || {trwrb,hplabs}!felix!dhw68k!feedme!doug
Feedme Microsystems:Inventors of the Snarf->Grok->Munge Development Cyclechiaravi@silver.bacs.indiana.edu (Lucius Chiaraviglio) (06/12/88)
In article <36@feedme.UUCP> doug@feedme.UUCP (Doug Salot) writes: >In pondering good topics of conversation for dinner parties, I >suddenly realized that I don't know what that branch of science >is called in which aging and death are studied (I don't believe >gerontology is considered a research discipline). Actually, I was under the impression that gerontology is supposed to be considered a research discipline, but not many people seem to be doing extensive (or any) work on it. > Could someone >enlighten me? (I'm sure many of you could, but I mean specifically >about the study of death.) I don't know about this one, but maybe thanatology would be the appropriate term? >Before I run out and subscribe to Death Today or Popular Dying, >does anyone want to give a rundown of current theory on the >subject? What cellular organelles are depletable (assuming >suitable nutrients are available from the environment)? Have >the mechanisms which determine whether (or how) a cell becomes >specialized and stops dividing been elucidated? No, these mechanisms have not been determined, although it is definite that aging occurs at the cellular level. Many people have thought that aging is the result of accumulated DNA damage, but this theory absolutely fails to explain how accumulation of DNA damage can lead to aging of individuals yet allow them to give rise to perfectly young offspring. A modification of this theory which has some experimental evidence for it (proposed by Robin Holliday) states that aging is the result of loss of epigenetic information about cell differentiation which is stored as methylation of cytosines in cytosine-guanosine sequences in the DNA -- this information is reset to zero in the germ line (which is "undifferentiated," or more properly at the ground differentiated state). Holliday believes that recombination in meiosis is responsible for this; could be, but I don't see why recombination should be required for this. At any rate, when the epigenetic information about differentiation is reset, damage to the epigenetic information would also be reset. I propose that the reason for aging (whatever the specific mechanisms) is that even in the absence of aging the ranks of any generation of most organisms are quickly reduced (by predation, starvation, disease, accidents, etc.) to numbers too small for selective pressures that affect them alone to have a significant effect on the evolution of species as a whole. Therefore, mutations whose deleterious effect is considerably delayed (Huntington's disease is a clinically-characterized example) will incur so little selective disadvantage that they will appear in the population faster than they are removed by negative selection. (Eventually, this will reach an equilibrium so that they are removed as fast as they appear.) Taken together, the effects of these delayed-effect deleterious mutations constitute aging. >Oh, and while I'm at it, what is the standard definition of human >death these days? Is it flatline for some time span? If so, what >area of the brain is being monitored? Are there estimates for the >amount of cellular damage as function of CNS (or CV) inactivity time? I'm not sure if the legal definition of human death has been entirely settled, although the trend has been to define it as corresponding to brain death. I'm not sure how long the EEG has to read flat for a patient to be pronounced legally dead, but a few minutes without oxygen destroys all but the most rudimentary functions of the human central nervous system; also, at least most types of neurons seem to die off if they are not stimulated sufficiently, but I don't know what the time frame is for this. -- Lucius Chiaraviglio chiaravi@silver.bacs.indiana.edu lucius@tardis.harvard.edu (in case the first one doesn't work) "NO DYING ALLOWED." -- The Maytag coin-operated washing machine instruction poster. "This would be nice!" -- graffitti seen on the Maytag coin-operated washing machine instruction poster in the Daniels laundry room in Currier House at Harvard University.
chiaravi@silver.bacs.indiana.edu (Lucius Chiaraviglio) (06/12/88)
In article <1894@silver.bacs.indiana.edu> I wrote: > No, these mechanisms have not been determined, although it is definite >that aging occurs at the cellular level. That should read as ". . .it is definite that some aspects of aging occur at the cellular level." That refers to the fact that mammalian cells can only divide for a limited number of times before senescing, and then die. I don't know if these experiments have been done for other vertebrates, but I would presume that the results would be similar. Note that mammalian cells can become immortalized by mutation; this is a necessary step for the attainment of a cancerous state but does not itself constitute a cancerous state. Incidentally, this is a good place to point out that treatments which reduce the level of methylation of DNA in mammalian cells, such as exposure to 5-aza-cytidine or 5-aza-deoxycytidine, reduce the lifespan (measured in terms of number of divisions) of mammalian cells in tissue culture; even without such treatment, loss of methylation correlates with aging, and occurs more rapidly in cells of short-lived species, but not at all in immortalized cells. Interestingly, an animal which has no methylation of its DNA in the first place, Drosophila melanogaster, does age; however, imaginal disks (precursors of the adult body which are stowed inside the larval body) can be serially transferred from one larva to another indefinitely, and never quit growing as long as this type of maintainance is kept up. -- Lucius Chiaraviglio chiaravi@silver.bacs.indiana.edu lucius@tardis.harvard.edu (in case the first one doesn't work) "NO DYING ALLOWED." -- The Maytag coin-operated washing machine instruction poster. "This would be nice!" -- graffitti seen on the Maytag coin-operated washing machine instruction poster in the Daniels laundry room in Currier House at Harvard University.
briscoe-duke@CS.YALE.EDU (Duke Briscoe) (06/12/88)
In article <1894@silver.bacs.indiana.edu> chiaravi@silver.UUCP (Lucius Chiaraviglio) writes: >No, these mechanisms have not been determined, although it is definite >that aging occurs at the cellular level. Many people have thought >that aging is the result of accumulated DNA damage, but this theory >absolutely fails to explain how accumulation of DNA damage can lead to >aging of individuals yet allow them to give rise to perfectly young >offspring. ... I don't think this is a valid point against the DNA damage accumulation theory. Some damage does occur to eggs and sperm as individuals age. People do become sterile with age (for various reasons, some of which may be related to DNA damage to germ cells). Germ cells with too much damage may result in miscarriages. Less damage may result in viable mutations, which may be harmful, neutral, or beneficial. Also, note that testicles are kept outside of the main body cavity where the temperature is slightly lower, which I believe is an adaptation to lower the rate of chemical mutagenic reactions. Perhaps this is related to the extended fertility of men versus women (once again, there can be other factors involved in this phenomenon). Has anyone seen this theory for the evolution of external testicles before?
chiaravi@silver.bacs.indiana.edu (Lucius Chiaraviglio) (06/13/88)
In article <31342@yale-celray.yale.UUCP> briscoe-duke@CS.YALE.EDU (Duke Briscoe) writes: |In article <1894@silver.bacs.indiana.edu> chiaravi@silver.UUCP (Lucius |Chiaraviglio) writes: | |>No, these mechanisms have not been determined, although it is definite |>that aging occurs at the cellular level. Many people have thought |>that aging is the result of accumulated DNA damage, but this theory |>absolutely fails to explain how accumulation of DNA damage can lead to |>aging of individuals yet allow them to give rise to perfectly young |>offspring. ... | |I don't think this is a valid point against the DNA damage |accumulation theory. Some damage does occur to eggs and sperm as |individuals age. People do become sterile with age (for various |reasons, some of which may be related to DNA damage to germ cells). This appears not to be due to DNA damage, although certain kinds of damage (such as chromosomes getting stuck to each other so that they nondisjoin) do hit progressively more eggs (because no more are made) as time passes. Animals become less fertile or infertile with age as the gametes quit functioning due to somatic aging, and also in females because of running out of eggs (no more eggs are made after the early part of life (before birth in humans)). |Germ cells with too much damage may result in miscarriages. Less |damage may result in viable mutations, which may be harmful, neutral, |or beneficial. The miscarriage selection mechanism does take place, but it wouldn't work quite well enough to prevent pre-aged offspring from being born -- offspring that are much sicker than mere aging (unless it were extreme) would do can be born, even if their genome is significantly damaged, such as aneuploidy of the sex chromosomes (including but not limited to Turner's Syndrome and Klinefelter's Syndrome), trisomies of chromosomes 13, 18, and 21 (Down's Syndrome), possibly trisomy 22, and monosomy of a piece of the short arm of chromosome 5 (Cri du Chat syndrome), as well as various mutations damaging much smaller pieces of the genome. | Also, note that testicles are kept outside of the main |body cavity where the temperature is slightly lower, which I believe |is an adaptation to lower the rate of chemical mutagenic reactions. The lowering of temperature that testicles experience relative to the body (a couple of degrees Centigrade) is not enough to lower the rate of chemical mutagenesis greatly. Also, if that were a significant factor, female mammals would likely have external ovaries. |Perhaps this is related to the extended fertility of men versus women |(once again, there can be other factors involved in this phenomenon). No, females of diverse animals become infertile first because they run out of (or at least run low on) eggs (no more are being made, as stated above) and due to accompanying hormonal changes that are also caused by somatic senescence (which may stop ovulation before every last egg has been depleted). Incidentally, a lot of animals die of old age before either males or females become sterile (although in nature something else gets them before old age does). |Has anyone seen this theory for the evolution of external testicles |before? I haven't seen this theory for the evolution of external testicles before, but it doesn't seem to wash in light of the above information. However, it is known that some step in spermatogenesis is significantly more heat-sensitive than everything else. Therefore, it seems that external testicles evolved when mammals (and maybe their immediate precursors) became warm-blooded, as a kludgy solution to this problem (would have been better to just fix the process to be less sensitive to heat, but evolution does not always produce the best possible result -- but what do you expect from something that depends on random mutations?). -- Lucius Chiaraviglio chiaravi@silver.bacs.indiana.edu lucius@tardis.harvard.edu (in case the first one doesn't work) Better active today than radioactive tomorrow. . . . . .but better radioactive today than inactive tomorrow. :-)
lmann@jjmhome.UUCP (Laurie Mann) (06/13/88)
In article <36@feedme.UUCP>, doug@feedme.UUCP (Doug Salot) writes: > In pondering good topics of conversation for dinner parties, I > suddenly realized that I don't know what that branch of science > is called in which aging and death are studied (I don't believe > gerontology is considered a research discipline). Could someone > enlighten me? (I'm sure many of you could, but I mean specifically > about the study of death.) Y'know, I'm not so sure there IS a "branch of science...in which aging and death are studied." However, the branch of sociology/religion in which death and dying are "studied" is called "eschatology." Back in college 10 years ago, I took a college course called "On Death and Dying" which was very interesting. Perhaps since biology is literally "the science of life," scientists are leery to formally study "death." Mengele may have been the last to study it with human subjects....... :-( \* This is the way the future is... Hacking net address: {harvard,ulowell}!m2c!jjmhome!lmann ** lmann@jjmhome.UUCP Working net address: harvard!anvil!es!Laurie_Mann (Stratus Computer) uS(n)ail: Laurie Mann, Stratus, M22PUB, 55 Fairbanks Blvd, Marlboro, MA 01752
blais@ut-emx.UUCP (Donald Blais) (06/13/88)
If you are interested in the biology of aging then the key words to look
for are GERONTOLOGY, LONGEVITY, and PROLONGEVITY. QP 85 and QP 86 are
the Library of Congress call numbers for these titles.
GERIATRICS is concerned with medicine for the aged. THANATOLOGY shows
up in some titles related to death.
--
Donald E. Blais ARPA: blais@emx.utexas.edu
Computation Center BITNET: blais%emx.utexas.edu@cunyvm.cuny.edu
University of Texas UUCP: {...}!ut-sally!ut-emx!blais
Austin, TX 78712 VOICE: (512) 471-3241heather@blia.BLI.COM (Heather Mackinnon) (06/14/88)
In article <1898@silver.bacs.indiana.edu>, chiaravi@silver.bacs.indiana.edu (Lucius Chiaraviglio) writes: > In article <31342@yale-celray.yale.UUCP> briscoe-duke@CS.YALE.EDU (Duke > Briscoe) writes: > |In article <1894@silver.bacs.indiana.edu> chiaravi@silver.UUCP (Lucius > |Chiaraviglio) writes: > > Animals become less fertile or infertile with age as the gametes quit > functioning due to somatic aging, and also in females because of running out > of eggs (no more eggs are made after the early part of life (before birth in > humans)). Human females are some of the only animals who outlive their time of sexual fertility. I can't believe that running out of eggs is a cause of menopause. Human females are born with some 100,000 eggs. If you assume that 25 eggs are used per year (2 per menstrual cycle, a very high estimate), a human female still has enough eggs for about 4,000 years of fertility. Also, if running out of eggs was a major cause of menopause, we would expect that women with a large number of children (each pregnancy causes a cessation of ovulation for roughly 2 years) to enter menopause significantly later than women who have fewer children. In fact, women tend to enter menopause at roughly the same age that their mothers did, regardless of the number of children borne. Hormone levels stop dropping in human females around the age of 25. They continue to drop until the hormone levels are insufficient to cause follicle ripening, ovulation and menstruation. The reasons for this are not well understood. The above is fact, as far as I understand. Conjecture follows. It may be that menopause is programmed to occur at a certain point in a woman's life, much as menarche occurs. Late childbearing is a risk to the mother and puts her other living children at risk also. Since human children are dependent upon their parents for such a long time, menopause may be a way of helping to insure that the parents stick around long enough for the children to achieve independence.
hes@ecsvax.UUCP (Henry Schaffer) (06/14/88)
I know I've seen the term "thanatology" (from the Greek root for "death".) However this compound word is not in my dictionary. --henry schaffer n c state univ
chiaravi@silver.bacs.indiana.edu (Lucius Chiaraviglio) (06/14/88)
In article <4810@blia.BLI.COM> heather@blia.BLI.COM (Heather Mackinnon) writes: >In article <1898@silver.bacs.indiana.edu>, chiaravi@silver.bacs.indiana.edu >(Lucius Chiaraviglio) writes: >> Animals become less fertile or infertile with age as the gametes quit >> functioning due to somatic aging, and also in females because of running out >> of eggs (no more eggs are made after the early part of life (before birth in >> humans)). > >Human females are some of the only animals who outlive their time of >sexual fertility. I can't believe that running out of eggs is a cause >of menopause. Human females are born with some 100,000 eggs. If you >assume that 25 eggs are used per year (2 per menstrual cycle, a very >high estimate), a human female still has enough eggs for about 4,000 >years of fertility. Problem is that not all of the oocytes have a chance to be used -- before puberty occurs, the great majority of them die. I forget the percentage that survives, but it is something horrendously small. In rats, this has been shown to be preventable (or at least reducible) by giving very young rats (some time fairly close to birth) extra amounts of some hormone (I forget the name of it -- this is from a Scientific American article of *many* years ago) which is ordinarily limiting for oocyte survival; the problem with this is that then too many eggs are released at each ovulation (conceivably this problem might be less severe in humans, which have stricter control over the release of eggs so that normally only one is released at a time). Nevertheless, untreated rats do (as you say below) die of old age before menopause. > Also, if running out of eggs was a major cause >of menopause, we would expect that women with a large number of children >(each pregnancy causes a cessation of ovulation for roughly 2 years) to >enter menopause significantly later than women who have fewer children. >In fact, women tend to enter menopause at roughly the same age that >their mothers did, regardless of the number of children borne. Good point. I don't know the answer to this one; however, if my memory serves me right, the supply of eggs is running low by the time menopause occurs. However, I shouldn't have said that it is a major cause. >Hormone levels stop dropping in human females around the age of 25. They ^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^ >continue to drop until the hormone levels are insufficient to cause follicle ^^^^^^^^^^^^^^^^ >ripening, ovulation and menstruation. The reasons for this are not well >understood. Huh? Which one do you mean? >The above is fact, as far as I understand. Conjecture follows. > >It may be that menopause is programmed to occur at a certain point in a >woman's life, much as menarche occurs. Late childbearing is a risk to >the mother and puts her other living children at risk also. Since human >children are dependent upon their parents for such a long time, menopause >may be a way of helping to insure that the parents stick around long enough >for the children to achieve independence. This might be a case for menopause in humans, but some animals (such as chickens) that normally do not survive long enough to attain menopause, and whose offspring grow up fast enough for menopause not to be a factor, do attain menopause if maintained under conditions suitable for unusually long survival. Back in very primitive times, this would have been the case for humans as well to a fair extent, since the life expectancy was something well under 30; my memory is fuzzy on the situation with respect to menopause for other primates, but I think they have a lifespan marginally long enough to reach menopause under conditions unusually favorable to survival (read carefully-maintained captivity). -- Lucius Chiaraviglio chiaravi@silver.bacs.indiana.edu lucius@tardis.harvard.edu (in case the first one doesn't work) Better to open your mouth and prove yourself a fool than to leave people hanging in suspense.
bzs@bu-cs.BU.EDU (Barry Shein) (06/14/88)
>I know I've seen the term "thanatology" (from the Greek root for >"death".) However this compound word is not in my dictionary. >--henry schaffer n c state univ I think "thanatology" has become a euphemism for funerary sciences, the preparation of corpses for display and burial. I once was involved in an occupational medicine research project at the New England Institute for Thanatology (or something like that), exposures to all the chemicals they use, particularly respiratory exposures. Very weird business that, I do suggest their trade rags, astounding, hints about increasing business during flu epidemics etc (the best one I read is put out by the Dodge Chemical Company, a major purveyor of thanatologicals (?!?!).) -Barry Shein, Boston University
jfh@cup.portal.com (06/15/88)
Henry Schaffer (HES@ECSVAX.UUCP) writes:
* I know I've seen the term "thanatology" (from the Greek root for
* "death".) However this compound word is not in my dictionary.
* --henry schaffer n c state univ
I don't know if that's a complaint or a question, but it's in my
dictionary (Webster's Ninth New Collegiate), and is defined as "the
description or study of the phenomena of death and of psychological
mechanisms for coping with them".
"Geriatric" gets "(plural but singualr in construction): a branch of
medicine that deals with the problems and diseases of old age and aging
people - compare gerontology",
"Gerontology" is "a branch of knowledge dealing with aging and the
problems of the aged".
haffer n c state univroot@bio73.unsw.oz (Karl Redell ) (06/15/88)
In New Scientist 29 October 1987 Pg. 39 in article titled: Faulty genes
lead to old age - Janet Mohun writes:
"...Biologists now know that methyl groups (-CH3) attached to a cell's DNA
can in some way control whether or not a particular gene is expressed. Any
change in methylation results in a corresponding change in control of gene
expression..."
"...Sebastion Fairweather suggested that the loss of methyl groups is a
normal part of ageing. This is because genes will remain "silent" or
unexpressed so long as specific cytosine bases within that gene remain
methylated. A gradual loss of methyl groups early in development is
therefore necessary to allow the normal pattern of gene expression to follow.
Fairweather, of the Radcliffe Infirmary in Oxford, said there is now
strong evidence that the rate at which methyl groups are lost from an
animal's cellular DNA is directly related to that animal's lifespan. DNA
from human cells loses methyl groups slowly as the cells age..."
"...Why should the loss of DNA methylation shorten a cell's life? The
theory is that, as cells age, some methyl groups are lost, perhaps because
the enzyme methylase is less active or because there is damage to the DNA.
This allows the expression of genes that previously were silent. The result
is that cells may produce proteins that are harmful to them, perhaps
activating oncogenes or inhibiting systhesis of DNA..."
"...In a review of the inheritance of epigenetic defects Holliday says
that defects in the cell would tend to appear after the loss of several
methyl groups, rather than just one, because genes tend to have a cluster
of methylated cytosine residues and not just one(Science,vol238,p163).
"It would be possible, therefore, to have many silent epigenetic
defects which produce a deleterious phenotype only after a given period
of time or a given number of cell divisions," he said."...pell@boulder.Colorado.EDU (Anthony Pelletier) (06/18/88)
The latest issue of cell (June 3. Vol 53.5) has a review of a new book on the mechanisms cell death that covers everything from the "Hayflick" limit to loss of membrane potential etc. It did not seem that Cell thought the book was great, but the mentioned a few other books that they thought were. Perhaps some real experts should be consulted here? The original poster (whose name escapes me) might find these books have some of the information he wants. happy reading tony
chiaravi@silver.bacs.indiana.edu (Lucius Chiaraviglio) (06/21/88)
Sorry if you have seen this before, but it appears to have gotten nuked the first time. Hit 'n' or whatever now if you have seen this before. In article <4810@blia.BLI.COM> heather@blia.BLI.COM (Heather Mackinnon) writes: >In article <1898@silver.bacs.indiana.edu>, chiaravi@silver.bacs.indiana.edu >(Lucius Chiaraviglio) writes: >> Animals become less fertile or infertile with age as the gametes quit >> functioning due to somatic aging, and also in females because of running out >> of eggs (no more eggs are made after the early part of life (before birth in >> humans)). > >Human females are some of the only animals who outlive their time of >sexual fertility. I can't believe that running out of eggs is a cause >of menopause. Human females are born with some 100,000 eggs. If you >assume that 25 eggs are used per year (2 per menstrual cycle, a very >high estimate), a human female still has enough eggs for about 4,000 >years of fertility. Problem is that not all of the oocytes have a chance to be used -- before puberty occurs, the great majority of them die. I forget the percentage that survives, but it is something horrendously small. In rats, this has been shown to be preventable (or at least reducible) by giving very young rats (some time fairly close to birth) extra amounts of some hormone (I forget the name of it -- this is from a Scientific American article of *many* years ago) which is ordinarily limiting for oocyte survival; the problem with this is that then too many eggs are released at each ovulation (conceivably this problem might be less severe in humans, which have stricter control over the release of eggs so that normally only one is released at a time). Nevertheless, untreated rats do (as you say below) die of old age before menopause. > Also, if running out of eggs was a major cause >of menopause, we would expect that women with a large number of children >(each pregnancy causes a cessation of ovulation for roughly 2 years) to >enter menopause significantly later than women who have fewer children. >In fact, women tend to enter menopause at roughly the same age that >their mothers did, regardless of the number of children borne. Good point. I don't know the answer to this one; however, if my memory serves me right, the supply of eggs is running low by the time menopause occurs. However, I shouldn't have said that it is a major cause. >Hormone levels stop dropping in human females around the age of 25. They ^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^ >continue to drop until the hormone levels are insufficient to cause follicle ^^^^^^^^^^^^^^^^ >ripening, ovulation and menstruation. The reasons for this are not well >understood. Huh? Which one do you mean? >The above is fact, as far as I understand. Conjecture follows. > >It may be that menopause is programmed to occur at a certain point in a >woman's life, much as menarche occurs. Late childbearing is a risk to >the mother and puts her other living children at risk also. Since human >children are dependent upon their parents for such a long time, menopause >may be a way of helping to insure that the parents stick around long enough >for the children to achieve independence. This might be a case for menopause in humans, but some animals (such as chickens) that normally do not survive long enough to attain menopause, and whose offspring grow up fast enough for menopause not to be a factor, do attain menopause if maintained under conditions suitable for unusually long survival. Back in very primitive times, this would have been the case for humans as well to a fair extent, since the life expectancy was something well under 30; my memory is fuzzy on the situation with respect to menopause for other primates, but I think they have a lifespan marginally long enough to reach menopause under conditions unusually favorable to survival (read carefully-maintained captivity). -- Lucius Chiaraviglio chiaravi@silver.bacs.indiana.edu lucius@tardis.harvard.edu (in case the first one doesn't work) Better to open your mouth and prove yourself a fool than to leave people hanging in suspense.