Lifespan vs Health span

[tigrxs]

Lifespan - the length of time for which a person, animal, or thing exists, whereas healthspan refers to

Health span - the number of years that someone lives or can expect to live in reasonably good health

The average lifespan has been steadily improving in the West, however, health span hasn’t; this could be because of things like life support, which is basically a living corpse, and various other treatments that keep a patient alive but leave them horribly ill. Modern treatments/medicines are good at keeping people alive but not healthy, this is why the gap between health span and lifespan is growing wider and wider every year. The difference is over a decade, this means the average person is living for years and years in sub-optimal health.

A common misconception is that people didn’t live very long in the past; this was caused by the high infant mortality rate which caused the average life span to be lowered greatly, infant morality has been lowered with basic interventions such as postnatal care, adequate nutrition, vaccinations, and treatment for common diseases.

The most common disease-related deaths are “fixed" with things like chemotherapy and life support.

Chemotherapy is a common treatment for cancer and has likely contributed heavily to the increase in lifespan. However, chemotherapy has horrible side effects which include:

• Fatigue
• Hair loss
• Easy bruising and bleeding
• Infection
• Anemia (low red blood cell counts)
• Nausea and vomiting
• Appetite changes
• Constipation
• Diarrhea
• Mouth, tongue, and throat problems such as sores and pain with swallowing
• Peripheral neuropathy or other nerve problems, such as numbness, tingling, and pain
• Skin and nail changes such as dry skin and color change
• Urine and bladder changes and kidney problems
• Weight changes
• Chemo brain, which can affect concentration and focus
• Mood changes
• Changes in libido and sexual function
• Fertility problems

If you’ve ever known someone who has used chemotherapy, you would know how bad it is for your health. Unfortunately, if you have cancer you dont have much choice, and even then it doesn’t have that high of a success rate at approximately 50% but this depends on the type of cancer, overall health, etc compared to the approximately 10% who received no chemotherapy.

Life support is typically used for extreme cases, these include:

• Lungs: In cases of near-drowning, pneumonia, drug overdose, a blood clot, and severe lung injury or disease, such as COPD and cystic fibrosis, and muscle or nerve diseases such as ALS and muscular dystrophy
• Heart: Sudden cardiac arrest or heart attack
• Brain: Stroke or a severe blow to the head

Life support uses a ventilator which are machine that act as bellows to move air in and out of your lungs

The common side effects of life support include:

• Atelectasis is a condition in which your lung or parts of it do not expand fully. This causes the air sacs to collapse and reduces the amount of oxygen that reaches your blood.
• Blood clots and skin breakdown can happen from staying in one position for long periods. When using a ventilator, you may need to stay in bed or use a wheelchair. This raises your risk of blood clots, serious wounds on your skin called bedsores, and infections.
• Fluid can build up in the air sacs inside your lungs, which are usually filled with air. This is called pulmonary edema.
• Lung damage can result from pushing too much air into your lungs or using too much pressure. Too much oxygen can also damage your lungs. Babies put on a ventilator, especially premature infants, may be at a higher risk of lung damage from excess oxygen therapy and lung infections in childhood and adulthood.
• Pneumothorax is a condition that develops when air leaks out of your lungs and into the space between the lungs and the chest wall, and sometimes into the muscles and tissues of your chest wall and neck. This leakage can cause pain and shortness of breath. It may cause one or both lungs to collapse. The air that enters the chest could also put pressure on your heart, resulting in a life-threatening situation that would require immediate placement of a tube in your chest to drain the air and decrease the pressure on your heart.
• Vocal cord damage from the breathing tube can damage your vocal cords. This can affect the passage of air into the lungs, especially in young children with smaller airways. Tell your doctor if you experience hoarseness or have trouble speaking or breathing after your breathing tube is removed.
• Weak diaphragm and other breathing muscles from long-term use of a ventilator can lead to some problems and delays in being taken off the machine.

https://publichealth.wustl.edu/heat...fespan-so-why-dont-more-people-know-about-it/

Survival Rates of Concurrent Chemo-Radiation versus Radiation Alone in Locally Advanced, Unresectable Head and Neck Cancers: A Retrospective Cohort Study - PubMed

Concurrent chemo-radiation (CRT) should be used as the standard treatment in patients who are medically fit. A Cisplatin or Carboplatin weekly regimen can be used as an alternative to a Cisplatin three-weekly regimen. Site of primary tumor N-stage, recurrent tumor, low RT dose (below 70 Gy), and...

pubmed.ncbi.nlm.nih.gov

Risks of Being on a Ventilator

A ventilator can raise the risk of infection such as pneumonia as well as other problems from short- or long-term use. Learn more about the possible risks of ventilator support.

www.nhlbi.nih.gov

 

[optimisticzoomer]

Based
If I got late stage cancer I'd just walter white maxx

 

[JohnDoe]

There's a good reason why a lot of people who are dying choose not to extend their lifespan with "treatment". You would rather want to live and be yourself for whatever time you have instead of being a chemo zombie and adding on a minor amount of time to your lifespan.

 

[Youㅤ]

ive had healthspan of 0 cuz my health ruined

youthspan is time ur in ur youth . "healthy" 60 year old is still oldcel . i youthspanmax

 

[Youㅤ]

my lifespan : 1000000000000000+ year

 

[Youㅤ]

childspan : time when ur growing & not done with sexual development

so like 15 years in human

 

[Youㅤ]

how can i regain my childspan ? i try to demethylate & partially childhormonemax with melatonin supp

 

[Youㅤ]

deathspan : time dead

deathspan : infinity <------ brutal

 

[Youㅤ]

i will cryonicsmax so i can have deathspan be impermanent tho . or at least broken into segments

 

[Youㅤ]

yeah the jooz have made goyim longer lifespan . after the retire their healthspan vanish so the jews can instead pull shekels off their medical bills

now the jooz r trying to increase healthspan cuz medical bills get too high cuz amerimutts eat too much goyslop fat burgercel mutts . the jooz increase healthspan so they can be wageslave longer

i will defeat ageing and increase youthspan so i dont live as oldcel muh healthspan cope

 

[Youㅤ]

healthspan of faggot and blackcel is very low . its cuz blak have lower childspan . and faggot have higher sexualspan cuz they sexually absued when in childspan

 

[Youㅤ]

TRT is cope for anti ageing

testosteronespan doesnt exist lol as a an ageing thing

A validated age-related normative model for male total testosterone shows increasing variance but no decline after age 40 years - PubMed

The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. However, to our knowledge, no such reference model exists in...

pubmed.ncbi.nlm.nih.gov

 

[Youㅤ]

must escape velocity

bornspan : time before born (cuz it take long process b4 ur born for ur genes tpo be create)

increased bornspan -> more likely to escape velocity

but i must increase lifespan so i can be a bit more likely to escape velocity

must increase youthspan & healthspan so ur less aged and unhealthy when new treatments u get less to worry about . also of course this could lead to greater maximum lifespan

CR ? id do with eTRF to emulate murid study . low caloric (not extreme CR)+ eTRF + CR mimetic could be strategic

 

[Youㅤ]

body temp import for slower ageing

Aspirin and Nonfebrile Waking Oral Temperature in Healthy Men and Women: Links with SWS Changes?
Aspirin lowered normal body temp by .14 celsius (.252 fahrenheit) in men

Recovery = 3 days after aspirin

[The normal body temperature lowering effect of aspirin in mice and its circadian rhythm]
Aspirin lowers body temp in mice

Transgenic Mice with a Reduced Core Body Temperature Have an Increased Life Span | Science

Hypotized state lowers body temperature

Cortisol raises body temperature

Vasodilation may increase heat loss . magnesiusm blocks calcium channels , relaxing muscles . this leads to vasodilation .

Homeostatic versus Circadian Effects of Melatoninon Core Body Temperature in Humans
“Administration of melatoninduring the day, when it is not normally secreted, decreases CBT by about 0.3 to0.4&deg;C, and suppression of melatonin at night enhances CBT by about the samemagnitude.”

“In one study (Dollins et al., 1994), doses below 1 mg(0.3 or 0.1 mg), which are claimed to reproduce physi-ological plasma levels of melatonin, failed to reduceCBT. On the basis of this finding, it could be suggestedthat only levels of melatonin in the pharmacologicalrange, but not in the physiological range, exert aneffect on CBT. However, reproduction of physiologicallevels of melatonin in blood may be useful to study theperipheral separated from the central effects of the 513hormone. Indeed, pharmacokinetic studies in animalsincluding primates (Cagnacci, 1997) have suggestedthat within the ventricular cerebrospinal fluid, levelsof melatonin similar to those observed during theendogenous production of the hormone may be ob-tained only by increasing its peripheral levels to thepharmacological range. Because cerebrospinal fluid isbelieved to represent the preferential route for mela-tonin to reach the hypothalamus, the site of integrat-ing centers for thermoregulatory processes, theadministration of low melatonin doses that maintainphysiological levels of the hormone in peripheralplasma for a limited period of time actually might beinsufficient and inadequate to reveal its central actionon thermoregulation.”

IGF-1 increases body temperature via anterior hypothalamic insulin receptors

Insulin acts on the hypothalamus to increase heat production and vasoconstriction

(mention: melatonin inhibits insulin secretion, perhaps this mediates melatonin’s effect on body temp?)

(another mention: fructose doesn’t raise insulin, implying a potential benefit of fructose over glucose)

Alcohol lowers body temperature

High body temperature slows the perception of time

W = wind , lowers body temperature at 32.5 degrees

Neuropeptide Y decreases thermogenesis

Leptin increases body temperature and leptin deficient mice enter torpor when deprived of food

“When fed ad libitum, mice null for GPR50 (Gpr50-/-) showed a modest (~0.5°C) reduction of CBT, that like in the Hcrt-UCP2 mice and the GPR83 shRNA mice, respectively, was observed only during the dark-active part of the day. In response to 24 h food deprivation, CBT of Gpr50-/- mice dropped up to 10°C. O2 consumption and CO2 production were also reduced, and mice entered a torpor-like state. The exact mechanisms by which GPR50 may affect thermogenesis remain to be elucidated. The experimental evidence collected thus far suggest that GPR50 can affect thermal responses to energy signals by directly reducing the responses to leptin and melanocortin during fasting in the ARC, and indirectly by suppressing TRH in the PVN, possibly normally inhibiting entry into a hypometabolic state (Bechtold et al., 2012).”

Long-term calorie restriction, but not endurance exercise, lowers core body temperature in humanscore body temperature in humans

Calorie restriction lowers body temperature in rhesus monkeys, consistent with a postulated anti-aging mechanism in rodents. | PNAS

Rapamycin Blocks Induction of the Thermogenic Program in White Adipose Tissue - PMC

Germ-free mice and anti-biotic treated mice had reduced body temp

Fat Maintenance Is a Predictor of the Murine Lifespan Response to Dietary Restriction - PMC

 

[Youㅤ]

body temp import for slower ageing

Aspirin and Nonfebrile Waking Oral Temperature in Healthy Men and Women: Links with SWS Changes?
Aspirin lowered normal body temp by .14 celsius (.252 fahrenheit) in men

Recovery = 3 days after aspirin

[The normal body temperature lowering effect of aspirin in mice and its circadian rhythm]
Aspirin lowers body temp in mice

Transgenic Mice with a Reduced Core Body Temperature Have an Increased Life Span | Science

Hypotized state lowers body temperature

Cortisol raises body temperature

Vasodilation may increase heat loss . magnesiusm blocks calcium channels , relaxing muscles . this leads to vasodilation .

Homeostatic versus Circadian Effects of Melatoninon Core Body Temperature in Humans
“Administration of melatoninduring the day, when it is not normally secreted, decreases CBT by about 0.3 to0.4&deg;C, and suppression of melatonin at night enhances CBT by about the samemagnitude.”

“In one study (Dollins et al., 1994), doses below 1 mg(0.3 or 0.1 mg), which are claimed to reproduce physi-ological plasma levels of melatonin, failed to reduceCBT. On the basis of this finding, it could be suggestedthat only levels of melatonin in the pharmacologicalrange, but not in the physiological range, exert aneffect on CBT. However, reproduction of physiologicallevels of melatonin in blood may be useful to study theperipheral separated from the central effects of the 513hormone. Indeed, pharmacokinetic studies in animalsincluding primates (Cagnacci, 1997) have suggestedthat within the ventricular cerebrospinal fluid, levelsof melatonin similar to those observed during theendogenous production of the hormone may be ob-tained only by increasing its peripheral levels to thepharmacological range. Because cerebrospinal fluid isbelieved to represent the preferential route for mela-tonin to reach the hypothalamus, the site of integrat-ing centers for thermoregulatory processes, theadministration of low melatonin doses that maintainphysiological levels of the hormone in peripheralplasma for a limited period of time actually might beinsufficient and inadequate to reveal its central actionon thermoregulation.”

IGF-1 increases body temperature via anterior hypothalamic insulin receptors

Insulin acts on the hypothalamus to increase heat production and vasoconstriction

(mention: melatonin inhibits insulin secretion, perhaps this mediates melatonin’s effect on body temp?)

(another mention: fructose doesn’t raise insulin, implying a potential benefit of fructose over glucose)

Alcohol lowers body temperature

High body temperature slows the perception of time

W = wind , lowers body temperature at 32.5 degrees

Neuropeptide Y decreases thermogenesis

Leptin increases body temperature and leptin deficient mice enter torpor when deprived of food

“When fed ad libitum, mice null for GPR50 (Gpr50-/-) showed a modest (~0.5°C) reduction of CBT, that like in the Hcrt-UCP2 mice and the GPR83 shRNA mice, respectively, was observed only during the dark-active part of the day. In response to 24 h food deprivation, CBT of Gpr50-/- mice dropped up to 10°C. O2 consumption and CO2 production were also reduced, and mice entered a torpor-like state. The exact mechanisms by which GPR50 may affect thermogenesis remain to be elucidated. The experimental evidence collected thus far suggest that GPR50 can affect thermal responses to energy signals by directly reducing the responses to leptin and melanocortin during fasting in the ARC, and indirectly by suppressing TRH in the PVN, possibly normally inhibiting entry into a hypometabolic state (Bechtold et al., 2012).”

Long-term calorie restriction, but not endurance exercise, lowers core body temperature in humanscore body temperature in humans

Calorie restriction lowers body temperature in rhesus monkeys, consistent with a postulated anti-aging mechanism in rodents. | PNAS

Rapamycin Blocks Induction of the Thermogenic Program in White Adipose Tissue - PMC

Germ-free mice and anti-biotic treated mice had reduced body temp

Fat Maintenance Is a Predictor of the Murine Lifespan Response to Dietary Restriction - PMC

i can PM full paper of ones behind paywall btw


but oh yeah about body temp , this all u need to see for to see the POGTENTIAL OF THE COPNCEPT :

^ CR DLEAY AGEING BUT BUT BUT BUT ......... LOW TEMP *SLOW* IT

 

[Youㅤ]

Aspirin lowered normal body temp by .14 celsius (.252 fahrenheit) in men

i am conduct study on aspirin iwil let know results

...

does any1 know about centenarian & facial development ? cuz does recession decrease lifespan ?

what r ways ageing programed ? telomre , apoptosis , gene expression (this main one prob and not just regulate from DNA muh muh muh Methylation)


avoid injuries to increase healthspan DO NOT GET SKIN INJURYS LIKE PAPERCUTS THEY DECREASE UNDAMAGEDSPAN

 

[Youㅤ]

how do the parasites relate to this ?

germ free mice lower bod temp and longer lifespan

normie parasites prob make liv shorter

wait no parasite cope the bigger picture is ecology

alonemax alonemax alonemax , from evolution perspecitve this mean u cant reproduce & therefore should postpne programed ageing . or maybe it just punish bad gene ... oh no that would be cruel .

high population density increase ageing to population ctrl . this why people ageing faster

these parasites just helping with this when population gets high disease spreads and war attavks

 

[Youㅤ]

nofap is crucial

nofapspan is the time b4 u ever coom

every time ur fap urt body counts a fap counter & u age mor to balance rpeprductive output

in adept at nofap cuz im asexual

asexual isnt inhernent btw dont listen to the faggots . its induced by things like CR


speaking of counters , obv telomere (or technically its telomere shortening RATE that correlate positiveky lifespan ) , but also heart rate


LOOk at this

 

[teefight]

Healthspan has obviously increased too with stuff like medicine, but I think we've hit a point where our bodies simply cannot keep up as they weren't built to live 60+ years.

I think this is the same shit with capitalism, the myth of "infinite growth", and we create this pseudo-solution with the stuff you talked about with chemo, and with the economy artificially creating inflation.

 

[Youㅤ]

Healthspan has obviously increased too with stuff like medicine, but I think we've hit a point where our bodies simply cannot keep up as they weren't built to live 60+ years.

I think this is the same shit with capitalism, the myth of "infinite growth", and we create this pseudo-solution with the stuff you talked about with chemo, and with the economy artificially creating inflation.

we were built NOT to live long

we were CUCKED

but we evolveing ... those apes get mor long life is the trned


AND now im getting deja vu agian WHY WHY WHY YYYYYYYYY


Y


and no u wrong . healthspan decreaaswe a lot .

ive had healthspan of 0 cuz my health ruined

 

[Youㅤ]

Healthspan has obviously increased too with stuff like medicine, but I think we've hit a point where our bodies simply cannot keep up as they weren't built to live 60+ years.

I think this is the same shit with capitalism, the myth of "infinite growth", and we create this pseudo-solution with the stuff you talked about with chemo, and with the economy artificially creating inflation.

death death death death death death death death


this our progrma bro its over LITERALLY READ JOSH MITTELDORFS BOOK on AGEInfg

 

[Youㅤ]

its such ageing and this recession ageing me such faster how to immortal hmmmmmm tell me u mortalcels escape velocity the key ? muh singulaury ? or whats the key brooooooooooo . i know its esxtmely feasible to stip ageing cuz its in biolgoy in us . meybe i monkmax and stuff find how

 

[Youㅤ]

SCHIZOMAXXINGF DELAYS AGEING DARKMAXXING MUH LIOGHT RESITRCTION (LR) LRLRLRLRLLRLLLRLRLR

DAKRMNAXXING SCHOZOMAXXING DLEAY AGEINGMAXCNNG

(darkmaxxing can make mor schizo i think)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925688/

 

[Youㅤ]

gud channels vvvvv . share more SHAREINF IS CAREING !

https://www.youtube.com/@AntiAgingBio

https://www.youtube.com/@chrismasterjohn

https://www.youtube.com/@NUSYLLSoM

https://www.youtube.com/@TheSheekeyScienceShow

https://www.youtube.com/@conqueragingordietrying1797

https://www.youtube.com/@raypeatarchive-oq1oo

Physionic

Detailed multi-study analyses, clear explanations of mechanisms underlying the results, and a sprinkling of cheeky humor. Learn your body, from the macro to the micro - welcome to Physionic. Credentials: - PhD Candidate in Molecular Medicine (Cell Physiology) - Masters in Exercise Physiology -...

www.youtube.com

https://www.youtube.com/@cottageremedies

https://www.youtube.com/@Dr_Oleg_Kulikov

https://www.youtube.com/@AgingJournal

https://www.youtube.com/@immortalityIMT

https://www.youtube.com/@verjuengungsforschung

https://www.youtube.com/@BrentNally

https://www.youtube.com/@longevitysummitdublin_

https://www.youtube.com/@immortalityorg

https://www.youtube.com/@BuyingTimePodcast

https://www.youtube.com/@EsotericGold_net

https://www.youtube.com/@matthewlake182

 

[tigrxs]

why?

 

[tigrxs]

gud channels vvvvv . share more SHAREINF IS CAREING !

https://www.youtube.com/@AntiAgingBio

https://www.youtube.com/@chrismasterjohn

https://www.youtube.com/@NUSYLLSoM

https://www.youtube.com/@TheSheekeyScienceShow

https://www.youtube.com/@conqueragingordietrying1797

https://www.youtube.com/@raypeatarchive-oq1oo

Physionic

Detailed multi-study analyses, clear explanations of mechanisms underlying the results, and a sprinkling of cheeky humor. Learn your body, from the macro to the micro - welcome to Physionic. Credentials: - PhD Candidate in Molecular Medicine (Cell Physiology) - Masters in Exercise Physiology -...

www.youtube.com

https://www.youtube.com/@cottageremedies

https://www.youtube.com/@Dr_Oleg_Kulikov

https://www.youtube.com/@AgingJournal

https://www.youtube.com/@immortalityIMT

https://www.youtube.com/@verjuengungsforschung

https://www.youtube.com/@BrentNally

https://www.youtube.com/@longevitysummitdublin_

https://www.youtube.com/@immortalityorg

https://www.youtube.com/@BuyingTimePodcast

https://www.youtube.com/@EsotericGold_net

https://www.youtube.com/@matthewlake182

why?

 

[BrahminBoss]

how can i regain my childspan ? i try to demethylate & partially childhormonemax with melatonin supp

explain demethylate? what else do u do for youthspan

 

[JohnDoe]

yeah the jooz have made goyim longer lifespan . after the retire their healthspan vanish so the jews can instead pull shekels off their medical bills

now the jooz r trying to increase healthspan cuz medical bills get too high cuz amerimutts eat too much goyslop fat burgercel mutts . the jooz increase healthspan so they can be wageslave longer

i will defeat ageing and increase youthspan so i dont live as oldcel muh healthspan cope

Improve your English, you have some interesting things to say but i can't understand you.

 

[Youㅤ]

explain demethylate? what else do u do for youthspan

ageing -> methylation change -> alomst all methylation gain -> puberty signalling

melatonin -> TET enzymes -> demethylate

https://www.sciencedirect.com/science/article/pii/S2211124716305022

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049665/

melatonin -> DNMT1 & MeCP2 less-> methylation less

for youthspan i melatonin 40 mg i low calorie low protein i darkmax i alonemax i am testing aspirin on body temp to cold bodymax i sleepmax i dont exercise

 

[Youㅤ]

Improve your English, you have some interesting things to say but i can't understand you.

my english is god 4 my age most youngcels are retards i actually know grammar very well like perfectly abnd good vocab 4 age but i grammarmin to repel lowIQcels who cant read my words or ignore me cuz they think i must be loq IQ this is effective gatekeeping strategy

 

[Youㅤ]

explain demethylate? what else do u do for youthspan

i will look more into the methylaytion biology im very ADGHD im not expert rn

also 4 youthspan oh no i keep forgetting hold on uh ...... oh yes i age regressionmax .

oooooooh and most importnatntly i do nofap altho i already say this message previs . luckily i only start masturbateing at 16.5 young so my nofapspan was pretty good but then i coomer , recently i do nofap . this is OP and if ur doing CR or mimetic u should also nofap cuz i think coom will negate the benefit confered from CR program . nofap is so important to age less cuz ageing all to balakcne reproductive output htats why late sexual devlopment is paired with longer life . ideally u dont just not coom but u dont get aroused cuz it produces coom and stuff . so try not to get hard become asexual asexualcels are more youthful usually and seems in past people knew this like monks dont coom so they live long . and obv porn is jewish and nfects ur brain makes u age . and haveing sex is spread parasites to u this will decrease lifespan unless healthy JB

 

[Youㅤ]

why?

watch all those yt channels to youmax

shareing is careing plz share thingys with mee e eee e eee e e e eeeee eee e e eeeeee....

 

[Donkeyballs]

watch all those yt channels to youmax

shareing is careing plz share thingys with mee e eee e eee e e e eeeee eee e e eeeeee....

Yah yah ma nigga. Oxidative stress, radiation, free radicals, parasites and even glucose play part in le aging.
High insulin/High IGF1

What High insulin/IGF1 causes:

Telomere Shortening: Telomeres form the ends of human chromosomes. Telomeres shorten with each round of cell division and this mechanism limits proliferation of human cells to a finite number of cell divisions by inducing replicative senescence, differentiation, or apoptosis. THEIR SHORTENING IS ASSOCIATED WITH CELLULAR AGING AND REDUCED CELLULAR LIFESPAN

LEPTIN/LIPID SYNTHESIS THROUGH SREBP1 PATHWAY (NO NIGGA STOP!)
SO DOES HIGH ESTROGEN IN MEN.

INFLAMMATION THROUGH NF-KB PATHWAY (SHIEEEET!) https://www.nature.com/articles/sigtrans201723

mTORC1 PATHWAY: CELL HYPERPROLIFERATION , ALSO LIPIDGENESIS DIRECTLY THROUGH ACTIVATION OF ENZYMES ACETYL-CoA CARBOXYLASE AND FATTY ACID SYNTHASE

FOXOs INHBITION THROUGH PIE3K/AKT PATHWAY (Huh? what are FOXOS NIGGA?)

FOXOs, play an important role in apoptosis, cell cycle control, oxidative stress resistance, and metabolism.
Foxos activate genes involved in anti oxidant defenses like superoxide dismutase (SOD) and catalase. They also perform DNA repair and regulate aptosis to control cells that are inflicted with damage and stress.
Insulin and IGF1 greatly inhibit FOXOs.

What upregulates FOXOs?

Caloric restriction: Because of muh lowered insulin, overconsumption of glucose which works synergistically to increase insulin

Sirtuins (SIRT1): Sirtuins are dependent on NAD+-deacetylases that can deacetylate and activate FOXOs, mainly FOXO3.

Thing is the most of the FOXOs upregulators are stress factors themselves like oxidative stress.

 

[yue]

its such ageing and this recession ageing me such faster how to immortal hmmmmmm tell me u mortalcels escape velocity the key ? muh singulaury ? or whats the key brooooooooooo . i know its esxtmely feasible to stip ageing cuz its in biolgoy in us . meybe i monkmax and stuff find how

yue are not well

 

[Youㅤ]

Telomere Shortening: Telomeres form the ends of human chromosomes. Telomeres shorten with each round of cell division and this mechanism limits proliferation of human cells to a finite number of cell divisions by inducing replicative senescence, differentiation, or apoptosis. THEIR SHORTENING IS ASSOCIATED WITH CELLULAR AGING AND REDUCED CELLULAR LIFESPAN

how relevant r telomeres to human ageing in ur opinion ?

mTORC1 PATHWAY: CELL HYPERPROLIFERATION , ALSO LIPIDGENESIS DIRECTLY THROUGH ACTIVATION OF ENZYMES ACETYL-CoA CARBOXYLASE AND FATTY ACID SYNTHASE

thots on mTOR inhibitors like rapamycin ?

FOXOs INHBITION THROUGH PIE3K/AKT PATHWAY (Huh? what are FOXOS NIGGA?)

FOXOs, play an important role in apoptosis, cell cycle control, oxidative stress resistance, and metabolism.
Foxos activate genes involved in anti oxidant defenses like superoxide dismutase (SOD) and catalase. They also perform DNA repair and regulate aptosis to control cells that are inflicted with damage and stress.
Insulin and IGF1 greatly inhibit FOXOs.

https://www.pnas.org/doi/full/10.1073/pnas.0801030105

Caloric restriction: Because of muh lowered insulin, overconsumption of glucose which works synergistically to increase insulin

fasting as well . which is big part of CR in murid study

Sirtuins (SIRT1): Sirtuins are dependent on NAD+-deacetylases that can deacetylate and activate FOXOs, mainly FOXO3.

do u think high NAD -> better ? i cant find data on NAD+ levles in children , but based on the trend from 20+ , children would have much higher NAD+ levels than a 20 year old .

Thing is the most of the FOXOs upregulators are stress factors themselves like oxidative stress.

yes exactly . hormesis is intrigueing , like bill haast live to 100 injecting snake venom

 

[Donkeyballs]

how relevant r telomeres to human ageing in ur opinion ?

telomerase play a role in the lifespan of a cell.
keep in mind that I said telomerase and not telomeres.
telomerase is an enzyme.
Telomerase counteracts the shortening that occurs of telomerase during DNA replication/cell division. This action maintains telomere length, allowing cells to continue dividing.

Cancer cells for example have active telomerase which is what enables them to divide indefinitely.
Thats what cancer is, the uncontrolled hyperproliferation of cells, in the forms of tumors as an example.
Telomeres function more as an indicator of aging.
Aging occurs because of cell death.
Cells usually divide around 50 times until their death. And telomerase like previously mentioned extends this division, hence the lifespan of the cell. That’s why low telomeres are associated with cellular aging and reduced cellular lifespan and as a person gets older their telomeres get shorter.

I like to put youth persevation as this.
Balance of anabolism and catabolism .
However there are “bad anabolism” in the sense of hyperproliferation of cells which lead to aging, cellular dysfunction because of unnecessary overgrowth that hinders you EXAMPLE: tumor growth, excess lipid/fat growth. At the end this excess fat = inflammation, factor of aging. and “good anabolism” as in the growth of needed and beneficial like growth of skeletal muscle tissue.

Same thing with catabolism.
“bad catabolism” being the wastage of important tissues contributing to your healthspan, like Muscle sarcopenia being bad catabolism.
ultimately starving and dying as the extreme of catabolism.
“Good catabolism” being limiting catabolism (same as limiting anabolism), and recyclement through Autophagy, AMPK, Sirtuins, FOXO proteins.

You also talked about mTORC inhibitors. Upregulated mTORC acts distinctly as an anabolic pathway that leads to cell growth and lipidgenesis as previously stated.
Anabolism inhibits catabolism this is obvious,
mTORC inhibits catabolic actions like Autophagy, so inhibiting mTORC promotes autophagy which is essentially the recycling of cells.

yes exactly . hormesis is intrigueing , like bill haast live to 100 injecting snake venom

Similar to FOXOs, telamarese is actually activated through cellular injury and stress factors that activates phosphorylases, and inactivated by phosphates, this is to helps cells cope with damage and mantain their telomere integritiy, but overwhelmed, this creates further complications which lead to cancer, this is why long telomeres (because of telamarese) is actually linked to cancer more than short telomeres (not directly saying that long telamarese are actually cause of cancer, but the REASON for it being that way)

Cancer is an overall relatively rare complication of short telomere syndromes

JCI - Long telomeres and cancer risk: the price of cellular immortality

www.jci.org

Familial cancers caused by telomere-lengthening mutations

JCI - Long telomeres and cancer risk: the price of cellular immortality

www.jci.org

Limited survival of cancer-prone mice with long telomeres
and etc.
And this actually makes sense because carcinogen and their promoters like free radicals and radiations apply to cellular injury and stress factors like I previously mentioned and increase telmarese which increase telomere lenght, which then lead to cancer and tumors because of active telamarese that leads to indefinite growth/division.
Simply put it, free radicals, oxidative stress and radiation as an example increase cancer risk and further complications through telamarese activation BUT telamarese itself is not the direct cause...
Again.. Telomeres are not the cause of this unwanted effects and none is normal active telamarese in cells, but when they do occur because of severe cellular injury and stress factors it can work as an indicator, while the toxins and stress factors are the actual inflictors.

Estrogen also activates telomerase, excess estrogen is bad and its a cause of why estrogen can cause cancer like breast cancer, it also depends on the estrogen receptors which upregulate telomerase through the TERT gene.

So what is the verdict with telomeres and telomerase? What do we want from them?
We want to increase lifespan of cells (divisions until death) while inhibitjng unecessary proliferation because it leads to more cell death overall and the actual problem and why which is the reason telomeres shortern and not actually mainly because of low telomerase activation.

do u think high NAD -> better ? i cant find data on NAD+ levles in children , but based on the trend from 20+ , children would have much higher NAD+ levels than a 20 year old .

Niacin for example contributes to NAD+ synthesis, supports energy production, DNA repair, cell activation pathways which does this through various pathways and enzymes like Sitruins that I mentioned, reduces oxidative stress and etc. overall this supports cellular lifespan and stability, higher NAD+ levels exhibit improved resistance to stress and better repair mechanisms, which can increase their lifespan and the number of divisions they undergo. And you are right on NAD+ decreasing over age.

This is an excerpt I copied: Other researchers, simply by changing a single factor, caused great increases in the longevity of the cultured cells. Simply using a lower, more natural oxygen concentration, the cells were able to undergo 20 more divisions. Just by adding niacin, 30 more divisions; vitamin E, 70 more divisions. Excess oxygen is a poison requiring constant adaptation.

Vitamin E like mentioned in the excerpt delays cellular senescence, inhibits cell proliferation and has anti-oxidant properties making it a useful vitamin in optimal levels, it inhibits telomerase BUT conserves telomeres.
Like how the thyroid increases calcium levels and PTH retains calcium

Caloric restriction is not to be confused with fasting, but they can be related.
Thing is that many people eat too much calories than actually needed and when most of it is junk food with stress-inducing ingredients/chemicals and much sugars and carbs which cause oxidative stress, AGEs thus aging, it's not very beneficial.

AGE's for example occur when sugar is exposed and interacts with proteins AND FATS, this is where the
muh cholesterol bad thing comes from.
AGEs modify cholesterol with a more pronounced effect on LDL cholestreol, which is why the "experts" say muh LDL is muh bad cholesterol and sheeeit.
When in reality it's glucose, AGEs and oxidative stress that cause cardiovascular disease and not cholesterol itself, CVD was pratically invisible until the 1900's and we used to have a muuuch higher intake of cholesterol back then.
Im not saying sugar is bad, but everything is filled with sugar and people think sugar is just the fucking cane sugar powder and not the glucose in carbs with high glycemic loads.

 

[Youㅤ]

his is why long telomeres (because of telamarese) is actually linked to cancer more than short telomeres (not directly saying that long telamarese are actually cause of cancer, but the REASON for it being that way)

yeah short telomeres cause cancer , long telomeres r result of cancer

telomerase play a role in the lifespan of a cell.
keep in mind that I said telomerase and not telomeres.
telomerase is an enzyme.
Telomerase counteracts the shortening that occurs of telomerase during DNA replication/cell division. This action maintains telomere length, allowing cells to continue dividing.

the question is how much telomerase is expressed in stem cells

and the question of how telomeres r relevant to human ageing . i mean short telomeres can cause senescent cells . its also thot that telomeres may affect gene expression , which IMO is very relevant to ageing .

You also talked about mTORC inhibitors. Upregulated mTORC acts distinctly as an anabolic pathway that leads to cell growth and lipidgenesis as previously stated.
Anabolism inhibits catabolism this is obvious,
mTORC inhibits catabolic actions like Autophagy, so inhibiting mTORC promotes autophagy which is essentially the recycling of cells.

yes autophagy is important for lifepsan extension . i believe it is evolutionarily programmed to age faster when food is abundant and slower when food is not , since when food is abundant so is reproductive capacity and faster ageing can balance this out .

And this actually makes sense because carcinogen and their promoters like free radicals and radiations apply to cellular injury and stress factors like I previously mentioned and increase telmarese which increase telomere lenght, which then lead to cancer and tumors because of active telamarese that leads to indefinite growth/division.
Simply put it, free radicals, oxidative stress and radiation as an example increase cancer risk and further complications through telamarese activation BUT telamarese itself is not the direct cause...
Again.. Telomeres are not the cause of this unwanted effects and none is normal active telamarese in cells, but when they do occur because of severe cellular injury and stress factors it can work as an indicator, while the toxins and stress factors are the actual inflictors.

well i heard bill andrews say telomerase also acts as a growth promoter . and this could promote cancer . but i dont think long telomeres promote cancer .

Estrogen also activates telomerase, excess estrogen is bad and its a cause of why estrogen can cause cancer like breast cancer, it also depends on the estrogen receptors which upregulate telomerase through the TERT gene.

hmm ... maybe AI isnt great then for anti ageing .

 

[Youㅤ]

"When letrozole was added to cultures, androgen-dependent increases in telomerase activity were not observed (Table 1). We inferred that androgen conversion into estrogen was necessary to activate telomerase, further implicating the ER as the pathway of telomerase activation by sex steroids in lymphocytes."


children have low sex hormones , but perhaps this would need to be paired with low FSH &/or luteinizeing hormone for an anti ageing hormonal profile .

 

[Youㅤ]

btw all my text just got erased over @Donkeyballs my reply was incoomplete

 

[Youㅤ]

well u see the message b4 the one b4 the one b4 this one has image , it show CR with high AGE in diet not live longer than ad lib

lowring AGE in diet make live longer

also about niacin is there any in vivo evidence of anti ageing benefit ? NAD starts decline in childhood so should youngcels boost NAD ? mor -> better ?

Caloric restriction is not to be confused with fasting, but they can be related.

okay well it is cuz in labs where they test CR on mice they fast them since they hastily eat their food they r given once per day . & fasting 4 22 hours in mice is long relative to 22 hours in human cuz mice metabolic rate higher

 

[Donkeyballs]

Scroll all the way down for more studies also

Sirtuins which NAD dependant:

The low levels of Sirt1 and Sirt6 could further destabilize telomeres and activate the DNA damage response and p53.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736325/#:~:text=the%20low%20levels%20of%20Sirt1%20and%20Sirt6%20could%20further%20destabilize%20telomeres%20and%20activate%20the%20DNA%20damage%20response%20and%20p53.

NAD starts decline in childhood so should youngcels boost NAD ? mor -> better ?

NAD is quite important and it expresses it effects through sirtuins.
So basically sirtuins are NAD dependent.
Sirtuins are important and they are known to support telomere lenght and its stability, sirtuins influence the upregulation of telomerase which as said, cause telomere lenght. And telomere shortening represses sirtuins which we dont desire.

A recent study demonstrates that telomere shortening represses sirtuins and increasing sirtuin activity stabilizes telomeres and improves telomere-dependent disease, suggesting that these two pathways are tightly intertwined.

So sirtuins are repressed by telomere shortening both directly and indirectly since it telomeres shortening also triggers the responses of the p53 which inhibit sirtuins which I will talk about.

Sirtuins are involved in mitochondrial function and repair, meanwhile p53 and foxos for example have a pronounced effect of inducing cell death and permament cycle arrest which secret SASP and its not good.

Then we have SIRT1 (a sirtuin) which is very different from other cirtuins since it regulates foxos and p53 in a way that it inhibits certain of their capabilties like cell death and permament cellular cycle arrest, because sirtuins as a whole induce DNA repair as mentioned rather than death and cell cycle arrest which I explaine all below.

Sirt1, p53 and FOXOs have quite complex interactions.
Sirt1 regulate and therefore inhibit certain p53 and FOXOs functions (this is good I will explain why) while p53 and FOXOs just inhibit sirtuins (mainly p53)

(Arrows represent upregulation and the flat line represents inhibition)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736325/

So you can see up here that telomere dysfunction (low telomeres) upregulate p53 and also cancel the cooperative feedback of sirtuins and telomeres. And since p53 inhibits sirtuins, sirtuins play a very important role in mitochondrial function.
So since no sirtuins because of p53 then mitochondrial dysfunction and then aging



Like I said, p53 and FOXOs are mainly activated through stress responses like free radicals.
FOXOs promote DNA repair and stress resistant, they also inhibit cell proliferation. But how? Well one of these ways is through cell arrest and cell apoptsis (cell death.)
This makes sense because it serves to stop the division and growth of dysfunctional cells, by killing the cells directly rather than reparing them DNA and through "good" catabolic processes.)

This leads to cell death (which may be necesarry in severe cell dysfunction) however if it dosent do that then it activates cell cycle arrest. Which can then lead to permament cell cylcle arrest also known as Cellular senescence
The same this with the p53 gene, this gene also has DNA repairing capabilities and etc but it's limited and overshadowed by it's primary action of inducing cell apoptsis, cell cycle arrest which can lead to cellular senescence.

Cellular senescence is a response to stress factors (from pathways like FOXOs and p53) in which the cell stops its cell cycle and stops dividing, growing AND is inmune to death for large periods of time.
In cellular senescence the cells secrete a high amount of variety of pro-inflammatory cytokines, chemokines, growth factors, and proteases. And this promotes aging and disease.
(this is known as SASP.) You can read more about SASP.

Senescence-associated secretory phenotype - Wikipedia

en.wikipedia.org

Cellular senescence also results as a consequence of telomere shortening btw.

Telomeres shorten as a result of cellular replication, leading to a permanent cell cycle arrest, also known as replicative senescence

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514392/#:~:text=Telomeres%20shorten%20as%20a%20result%20of%20cellular%20replication%2C%20leading%20to%20a%20permanent%20cell%20cycle%20arrest%2C%20also%20known%20as%20replicative%20senescence

Take it like this:
Cells in permament cell cyclee arrest, which is cellular senescence, act like parasites that release pro-inflammatory and aging factors, (known as SASP.) this occurs as a response to cell dysfunction and damage in order to stop the hyperproliferation of these harmful and dysfunctional cells, but we want to minimize this form of coping that comes from the stress responses that FOXOs and the p53 gene receives through stress factors.

BACK TO SIRTUINS (which are NAD dependent)

So as I said sirtuins modulate and regulate FOXOs and p53 gene. But how?

By modifying the histones through deacetylation, deacetylation results in gene repression.
Sirtuins affect the behavior of FOXOs and p53 through deacetylating , while not inhibiting them completely since it does this by targeting certain lysines, the role of SIRT1 isn't to act as a complete FOXO and p53 antagonist, but as an inhibtor of some of their certian pathways which are cell death and cell senescence pathways.

So in p53, These certain lysines that SIRT1 targets modulates p53, more specifically siruitns modulate p53 by:
decreases its ability to activate target genes involved in cell cycle arrest, apoptosis, and senescence.
Sirtuins inhibits certain p53 pathways that activates pro-apoptotic genes such as BAX, PUMA, and NOXA).
Meanwhile not repressing p53 capabilities like dna repair.
p53 can also directly interact with mitochondrial proteins to promote the release of cytochrome c. (which SIRT1 inhibits)

Basically:
p53 =
1.activating the transcription of pro-apoptotic genes such as BAX, PUMA, and NOXA
2.Interact with mitochondrial proteins to promote the release of cytochrome c, leading to the activation of the caspase cascade and cell death.
3.Promotes cellular senescence
4. Inhibits sirtuins

Its activation in response to DNA damage leads to cell growth arrest, allowing for DNA repair (good), or directs cellular senescence or apoptosis (mainly undesireble)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175209/

Sirtuins
SIRT1 =
Inhibit certain p53 and FOXOs cell death and senescence functions through deacetylation of certain lysines which inhibit these functions mentioned above.

Rest of sirtuins= Promote cell and dna repair, mitochondrial function and oxidant resistance.

This telomere-sirtuin link also provides an entry point for therapeutic modulation through the administration of the NAD(+) precursor nicotinamide mononucleotide. Our studies show that increasing NAD(+) levels stabilizes telomeres and dampens the DNA damage response and p53 in a partially Sirt1-dependent manner.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736325/#:~:text=This%20telomere%2Dsirtuin,Sirt1%2Ddependent%20manner.

The NAD(+) supplementation associated increase in sirtuin activity in telomerase knockout mice improves mitochondrial biogenesis and function as reflected by increased expression of mitochondrial biogenesis factors, increased electron transport chain activity of complex I and IV and elevated mtDNA copy number.2

Sirt1 is expected to affect several cellular processes including modulation of histones and the epigenome, generalized DNA repair pathways, all of which could act cooperatively to prevent disease and aging.10

Deacetylation of FoxOs by Sirt1 in osteoblasts and osteoclasts stimulates bone formation and inhibits bone resorption, making Sirt1 ligands promising therapeutic agents for diseases of low bone mass

Sirtuins and FoxOs in osteoporosis and osteoarthritis - PubMed

The sirtuin family of NAD⁺-dependent protein deacetylases promotes longevity and counteracts age-related diseases. One of the major targets of Sirtuins are the FoxO family of transcription factors. FoxOs play a major role in the adaptation of cells to a variety of stressors such as...

pubmed.ncbi.nlm.nih.gov

SIRT1 helps FOXOs induce temporary cell cycle arrest, allowing cells to repair damage without undergoing apoptosis or permanent senescence.

SIRT1-mediated deacetylation promotes the expression of genes involved in DNA repair, aiding in the maintenance of genomic stability.

Deacetylation by SIRT1 enhances the ability of FOXOs to activate genes involved in antioxidant defense, such as manganese superoxide dismutase (MnSOD) and catalase, which help to neutralize reactive oxygen species (ROS).

I wish posts could have bookmarks and links like in goodle docs so I could organize everything betther.

 

[Donkeyballs]

w

I also noticed you said in a thread: https://looksmax.org/threads/dr-bil...ongation-here-are-some-of-my-thoughts.875492/

I’ve also thought about p53 (p53 activation can either induce cell growth cycle arrest and DNA repair, apoptosis, or cellular senescence) and wondered if it’s possible to augment the chances so that the path of cellular growth cycle arrest and DNA repair occurs more often relative to apoptosis and cellular senescence.

My resposne actually explains the interaction between sirtuins (SIRT1) and its interaction between this apoptic and cellular senescence pathways of p53.
Since SIRT1 inhibits these pathways that you dont want from p53
And overall, NAD upregulates sirtuins!! So this is important for the question

AKA: NAD HELPS TELOMERE AND TELOMERASE

 

[Youㅤ]

@Donkeyballs

Sirtuins which NAD dependant:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736325/#:~:text=the%20low%20levels%20of%20Sirt1%20and%20Sirt6%20could%20further%20destabilize%20telomeres%20and%20activate%20the%20DNA%20damage%20response%20and%20p53.

okay so i see evidence for NAD-dependant sirt1 function practical for telomere length preservation

its intrigueing that SIRT1 may reduce apoptosis , if this is true in vivo in humans for increased NAD+ levels i would expect NADmaxxing to ameliorate tissue atrophy with age .

but how practical is raiseing NAD+ in humans ? precursors seem to work for raiseing NAD+ , but is this meaningful to ageing process ? will u be biologically younger down the road if u increase NAD+ ? & how to increase sirtuins themselves ?

 

[Youㅤ]

so sirt1 OVEREXPRESSION in mice does increase telomerase & terc dependently increase telomere legnth compared to wild type ! if this translates to humans , i would want to sirt1max

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010065/figure/fig3/

 

[Youㅤ]

i think the big question is : can we use things to modulate sirtuins , telomerase etc in ways to meaningfully ameliorate telomere shortening ?

like i get the theory , i get the mechanisms exist , but will messing with the baseline in our own lives slow telomere shortening by like at least 10% ?