• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
- - - - -

SENS gaps, like a gerontologists reply


  • Please log in to reply
9 replies to this topic

#1 treonsverdery

  • Guest
  • 1,312 posts
  • 161
  • Location:where I am at

Posted 06 August 2005 - 01:36 AM


Word of courage there's a faint chance I might wipe the floor with sens n wilt here but as we know there are 40k year old plants that have functioning nDNA mtDNA, ribosomes, much like our own. That human systems are improvable to match that is natural.

There are different aging mechanisms. SENS only appears to cover cyte area

Newscientist has published a popular version of the science of mosaic chromosome people, these are people have phenotypes with items like patterned sweat checkerboards as clumps of body tissue use different entire genes. Women that have different versions of their two >< chromosomes at different tissue clumps have patterned sweat checkerboards. "Almost every woman is a mixture of two genetically different types of cell, and sometimes these cells can come into conflict with dramatic effect. We now believe that women's dual nature can split them into identical twins, divide them into discrete zones of disease"reference http://www.newscient...=mg17823944.200


It is published that octopus n salmon have organ directed senescence: remove the organ they live multiples longer.

A fiesty gerontologist might argue:
beyond cyte functional sens there is possible evidence that humans may have developmental program:

20th century brain grows till 10 with most people
puberty
gray hair patterns:
aside from pattern baldness one notices obvious patterning of gray at temples. with pattern baldness scalp hair transplanted to non bald area thrives, hair transplanted to patterned ares dwindles. Thinking on not-from-the-bottom-up bulk tissue effect: does gray hair transplanted from temples elsewhere go to original color. a few of my hairs have gone from gray to natural color. This transplant idea is rapidly testable, moving that to a human or mouse with mosaic chromosome dermis that has obvious varying rates of aging we may identify a new aging mechanism to conquor.

Breed Dr. Austad's long life Idaho wilderness wild type mouse with an
ordinary lab mouse to create daughter mouse with tissue mosaicism. tissue macromosaicism is then studied to describe the factors that cause, block, ameliorate the mouse's "age sag" spots with various organ systems just like characterizing the macro perspire non perspire spots on a mosaic human.

briefly: humans show developmental patterns not sourced from immediate area tissues at different times of life. brain growth, puberty, head hair patterns. These may also direct aging. Mosaic studies will test mechanisms.

telelogical nonsense:
There might be a genetic value placed on elders that have senescence programming . That is a tropism towards just the right quantity of community elderlyness builds a group's fitness. SENS is perhaps commingled with the idea that:
genes make it that we live till we reproduce, then raise kids, scientists go on to speculate that why we have oldness rather than salmon or octopus like death is related to the value of wise elders to survival. Genes that create wise elders contribute to group fitness, thusly gene survival. It is equally valid to note that a surplus of elders uses calories n changes decision making. If the gene argument is valid it is also potentially valid to note: the elderly may be programmed to wear out rapidly. It creeps me out but the unneeded Eskimo walking out onto the ice floe or the rapid catastrophic senescence of the emotionally nonattached tilt, just a wee bit, to gene programming.

opposing that argument is that S shaped curves like senescence are common to numerous processes, sens proceeds from the idea that the mean nasty high grade slope of elderly death is a nonspecific cumulative cytological thing rather programmed phenomena. Mosaic mice may tell.


Technology Yay this is basically supportive.

different than my perception of wilt, radio controlled DNA technology creates latitude to work with rapid proliferation tissues like lung, Gi tract, dermis.

MIT letter to nature about Ghz microantenna that switches DNA chemistry at breathing rates. K. Hamad-Schifferli, J.J. Schwartz, A.T. Santos, S. Zhang, J.M. Jacobson, “Remote electronic control of DNA hybridization through inductive coupling to an attached metal nanocrystal antenna”, Nature, 415 (6868), 152-5, (2002) http://www.nature.co...415152a_fs.html

That radio control technology may be a much more user happy technology to address legal cyte proliferation with tissues like GI tract that renew rapidly . I've also read that viruses which create silver nanoparticles have been created. That suggests creating an antenna virus that is radio controllable.

A different way to control mitochondia:

I thought of a way to best the: short mtDNA grab the enzymes, with thenonfunctional mitochondria ratio population result. with that idea there are Two mitochondrial DNA types: NormalmtDNA n NaughtymtDNA I think that dosing the organism with treated DNA that is more rapidly assimilated when NaughtymtDNA replicates is possible. The treatment is isotopic substitution. NaughtymtDNA that have a bunch of deuterated atoms will bog down their own replication due to the isotope effect. I may have verified that. That means that a cyte with both NormalmtDNA n NaughtymtDNA environmentally supplied with isotopically loaded DNA (molasses DNA) will favor reproduction of the high functioning normal DNA That is a way to youthify, that is change the ratio to favor normalmtDNA With old cytes like those of the elderly where up to 4/5 of the mitochondria n mtDNA are from NaughtymtDNA. Isotopic molasses DNA moves the system to favor normal mitochonrial dna.

I think that creating molasses DNA then targeting it to tissues with the MIT Ghz radio control chemistry thing creates the capacity to adjust rate of tissue activity n proliferation. Thats a way to address tissues like lungs n dermis GI tract that have rapid proliferation that might challenge "wilt". It also addresses the heart n brains as their mitochondria reproduce. The antenna virus has utility here as well.


Funny things:
telomeres are compared to shoelace tips. I think molasses DNA might be a little like um, wilderness garment gear spring tubes, I mention that as rather than having or not having telomeres one might prefer a telomere topology controller. with radio control at breathing rate.

bacteria without mitochondria are published, do they age, or do they...

regarding the ability of organisms to degrade gunk (glycosylation lipofuscin idea) There's a thing called hopanoid that is like cholesterol with more \/\/\/ The mass of hopanoid on earth is equal to the mass of plant matter. Plants given more CO2 double or better their growth. animals might degrade hopanoid I don't know. cholesterol is a known gunk. Pills that control cholesterol save lives. Pills that stimulate the liver to create enzymes might degrade hopanoids, a new potentially valuable gunk removal lifespan improver.

Treon

#2

  • Lurker
  • 1

Posted 06 August 2005 - 04:28 AM

gray hair patterns:
aside from pattern baldness one notices obvious patterning of gray at temples. with pattern baldness scalp hair transplanted to non bald area thrives, hair transplanted to patterned ares dwindles. Thinking on not-from-the-bottom-up bulk tissue effect: does gray hair transplanted from temples elsewhere go to original color. a few of my hairs have gone from gray to natural color. This transplant idea is rapidly testable, moving that to a human or mouse with mosaic chromosome dermis that has obvious varying rates of aging we may identify a new aging mechanism to conquor.


Excellent point. There is definitely a mosaic pattern of aging in tissues with some tissues aging faster than others and becoming the weak link to a longer lifespan as we get older. A 50 year old man can die from a "bum ticker" (ala Sin City) yet have a relatively healthy liver, brain, kidneys, etc.

Speaking of aging patterns this reminds me of a radioactivity poisoning study I came across (I have the reference somewhere) where seed apoptotic cells were observed that seemed to communicate an apoptosis or senescence factor that induced a similar fate to surrounding cells. It could well be that our tissues are populated with such senescence seed cells that under certain circumstances are triggered to begin a programmed phase of aging. The pattern that some aging phenotypes show would - such as male pattern baldness or grey patterning - suggest the existense of an advancing wave of senescence across tissues.

#3 Mark Hamalainen

  • Guest
  • 564 posts
  • 0
  • Location:San Francisco Bay Area
  • NO

Posted 06 August 2005 - 09:05 PM

Campisi has found senescent cells to be toxic to their local environment, and de Grey has suggested a mechanism for anaerobic cells being toxic since they release electrons through their plasma membrane. So the existence of such cells is fully expected in the damage accumulation model of aging. I'd like to see the paper you were thinking of though, if you can find it.

#4

  • Lurker
  • 1

Posted 08 August 2005 - 04:17 AM

I'd like to see the paper you were thinking of though, if you can find it.


Still trying to find it - using Spotlight (new Mac OS X.4 global search feature - I have thousands of mostly uncategorised PDF's on my disk) and all.. But no luck yet. At least you have come across this concept before so you know what I am talking about. One could test the hypothesis whether having such cells become silenced prior to propagating the senescence message would extend functional lifespan. A relatively easy task in a model org such as C. elegans providing such cells could be identified and perhaps have their message blocked by RNAi? Alternatively since the message is extracellular an antibody could be generated against the ligand?

#5 Mark Hamalainen

  • Guest
  • 564 posts
  • 0
  • Location:San Francisco Bay Area
  • NO

Posted 08 August 2005 - 04:33 AM

Here's an excerpt from a recent paper by Dr. Campisi

Bad Neighbors—Senescent Cells Alter Tissue Structure and Function

How might senescent cells promote aging phenotypes or age-related pathology? Because tissues have a fairly constant number of cells, the accumulation of nondividing senescent cells may compromise tissue renewal or repair. In addition, among the genes that are upregulated by the senescence response (Shelton et al., 1999, Chang et al., 2000 and Zhang et al., 2003), many encode secreted proteins that can alter the tissue microenvironment thus alter tissue structure and function. Both possibilities are viable, but at present evidence for the latter possibility is strongest.

The factors that are secreted by senescent cells vary depending on the cell type. Among the major mammalian cell types, the most thoroughly studied with regard to the senescent secretory phenotype are fibroblasts, which synthesize and maintain the stromal support for virtually all renewable epithelial tissues. Senescent fibroblasts secrete high levels of several matrix metalloproteinases, epithelial growth factors, and inflammatory cytokines (reviewed in Krtolica and Campisi [2002]). In many ways, the secretory phenotype of senescent fibroblasts resembles that of fibroblasts undergoing a wounding response, which entails local remodeling of the tissue structure (Grinnell, 2003). The wounding response also entails local inflammation, a frequent occurrence in aging tissues and proposed initiating or causative factor in a variety of age-related diseases, including atherosclerosis and cancer (Longo and Finch, 2003). The senescent secretory phenotype also resembles that of fibroblasts associated with some carcinomas. These carcinoma-associated fibroblasts are components of the so-called reactive stroma, which facilitates the progression of epithelial cancers (Olumi et al., 1999, Park et al., 2000 and Tlsty and Hein, 2001). Thus, senescent cells might contribute to aging and age-related pathology by stimulating chronic tissue remodeling and/or local inflammation, which would compromise tissue structure and function (Figure 2A). In addition, senescent cells might stimulate the proliferation of cells that harbor preneoplastic mutations (Figure 2B).


Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad
neighbors. Cell. 2005 Feb 25;120(4):513-22.

Might not be the one you were thinking of, but she includes comprehensive references. I'm browsing through them now. Also attached the paper for convenience.

#6 Mark Hamalainen

  • Guest
  • 564 posts
  • 0
  • Location:San Francisco Bay Area
  • NO

Posted 08 August 2005 - 04:42 AM

providing such cells could be identified and perhaps have their message blocked by RNAi?


From what I've read so far, there are some specific protein factors involved, so RNAi may be useful. There is a limit to the healing power of shutting things down though... obviously these proteins would have other functions than to cause trouble.

This is the sort of thing that should be considered SENS scaffolding, i.e. not part of the ideal solution, but useful as backups while the ideal solutions are developed.

#7 Mark Hamalainen

  • Guest
  • 564 posts
  • 0
  • Location:San Francisco Bay Area
  • NO

Posted 08 August 2005 - 04:59 AM

Knocking out the inflammation mechanism could be highly beneficial if we can substitute its useful effects with other medical technology.

#8 treonsverdery

  • Topic Starter
  • Guest
  • 1,312 posts
  • 161
  • Location:where I am at

Posted 09 August 2005 - 03:28 AM

Osiris writes:

Knocking out the inflammation mechanism could be highly beneficial if we can substitute its useful effects with other medical technology


I appreciate that idea. Prometheus wrote:

There is definitely a mosaic pattern of aging in tissues with some tissues aging faster than others and becoming the weak link to a longer lifespan as we get old


well, the Newscientist mechanism of mosaicism is more like part of a liver has a different genome from the other part of the same liver. That is because with mosaic women sometime's one parent's genes direct tissue formation, sometimes the other parent. The sweat checkerboard is literally like spots on a dalmation. To verify a different-than-SENS part of aging: with a mosaic mouse, each parent with notably different aging phenotypes; a researcher might study the difference between saggy age flesh mosaic areas, if any, on a mostly long life mouse compared with a pure ordinary lifespan mouse. If the saggy flesh mosaic areas are less saggy then there's a nontissue originating aging function or program to be studied n conquered. Idaho wildereness mice are published (Austad) as living as long as various medically lifespan improved mice. A mosaic between Idaho wilderness mouse n lab mouse is suggested.

Aside from cyte tissue mechanisms of senescence like SENS there is the hint of evidence that mammals have a social function feedback illness or senescence program. Among non humans ants, if isolated, will rapidly die 72 or 96 hrs. Researchers have found that when the ants are allowed to even briefly communicate with foreleg touching n face rubbing, they live. Ants have a non-tissue-up non-SENS death program that operates if they don't get the right social feedback.

The library's AARP magazine briefly mentions a study that people under stress have shorter telomeres. I've read a "what happens to people when they retire? They die, I'm putting off retirement" sentiment. perhaps humans have an "ant effect"

If social contact matters to elderly lifespan, as suggested with the Dawkins gene survival value of socially useful elders, then things like SSRIs, PEA (love effect chocolate chemical) or perhaps even artificial touch sources like those massager chairs might make the elderly live longer. It'd be effective to study n verify the "ant effect" with apartment dwelling solo mammal pets v. multipets. Viewing large numbers, have vetrinarians recorded meaningful lifespan differences between solo n multipet environments. If they have it suggests mammal ant effect. There's further value of the pet study with finding the chemistry of this potential different than SENS "decline program" then finding effective treatments.

I don't know if the ant effect is authentic senescence, that is a gradual change, with ant program lifespan, or mammal lifespan linearly graphable with touch n social quantity, or if it more like a nutrient deficiency where a person with years of nonadequate amount lives the normal time if they get adequate vitamins from the last third of life on. There is also a pro-SENS way of looking at this: it may be that a normal body produces a base level of a chemical. The ant effect may be the result of a nerve system change to the amount of that chemical which like pH buffering, if changed too far causes death. a simple mechanism differs from senescence. Mammal Stress->cortisol ->regulation of cyte division + osmotic environment + much more ->apparently nonspecific tissue noncompetency vaguely like aging differs from an "age program" which makes me think that the SENS seven might adequately address the ant effect on cytes if it is gradual.

Treon"

well, thats kind of like two non SENS mechanisms to study n conquer.

Edited by treonsverdery, 09 August 2005 - 04:29 AM.


#9 Mark Hamalainen

  • Guest
  • 564 posts
  • 0
  • Location:San Francisco Bay Area
  • NO

Posted 09 August 2005 - 04:11 AM

To verify a different-than-SENS part of aging: with a mosaic mouse, each parent with notably different aging phenotypes; a researcher might study the difference between saggy age flesh mosaic areas, if any, on a mostly long life mouse compared with a pure ordinary lifespan mouse.


Tissue specific gene expression is done routinely in drosophila, and on large scales. [1][2]

perhaps even artificial touch sources like those massager chairs might make the elderly live longer


Owning pets is a better source of this effect I think.

[1] Helfand SL, Rogina B. Genetics of aging in the fruit fly, Drosophila melanogaster. Annu Rev Genet. 2003;37:329-48. Review.

[2] Luc Poirier and Laurent Seroude. Genetic approaches to study aging in Drosophila melanogaster Journal of the American Aging Association 27:in press,2005 (http://seroudelab.bi...pdf/poirier.pdf)

#10 treonsverdery

  • Topic Starter
  • Guest
  • 1,312 posts
  • 161
  • Location:where I am at

Posted 09 August 2005 - 04:33 AM

There is also a SENS way of looking at a mammalian ant-effect: it may be that a normal body produces a base level of a chemical. The ant effect may be the result of a nerve system's change to the amount of that chemical which like pH buffering, if changed too far causes death. a simple mechanism that differs from senescence. Mammal Stress->cortisol ->regulation of cyte division + osmotic environment + much more ->apparently nonspecific tissue noncompetency vaguely like aging differs from an "age program" which makes me think that the SENS seven might cure the ant effect on cytes if it is gradual.

The drosophila references are appreciated.




2 user(s) are reading this topic

0 members, 2 guests, 0 anonymous users