Aspirin may replicate the benefits of fasting, while avoiding its risks

haidut

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I just made a post about fasting raising risk of early death by about 30%. On the other hand, fasting has been shown to lower biomarkers of inflammation as well as increase autophagy, with at least the former being undeniably beneficial. We already know from other studies that the benefits of fasting are largely due to lower levels of endotoxin (LPS) as well as restriction of intake of specific amino acids such as tryptophan, methionine, cysteine, arginine, glutamate, etc. Thus, if one were to eat food deficient in those nutrients while also keeping the microbiome in check with charcoal, insoluble fiber, antibiotics, etc then one would not need to restrict calories. However, keeping all these rules in mind can get pretty exhausting and invariably people slip on their dietary rules. So, instead of playing Russian roulette with fasting and hoping it won't lead to an early death, wouldn't it be be nice if one could get those benefits of fasting but without the risks, while also not restricting calories, specific nutrients, or worrying about the microbiome? The study below presents evidence that taking aspirin daily may be such an all-in-one caloric restriction mimetic (CRM). The daily HED of the mice dose the study experimented with was about 8mg/kg, which means that taking 2 tablets (325mg each) aspirin daily should be able to replicate for most people the design of this study.

Aspirin Recapitulates Features of Caloric Restriction - PubMed
"...Based on the results described in this paper, aspirin may be classified as a CRM. Indeed, aspirin fulfills all the criteria of a CRM (Madeo et al., 2014) as it (1) reduces protein acetylation by virtue of its ability to inhibit the acetyltransferase activity of EP300, (2) stimulates autophagic flux, and (3) has no cytotoxic activity. Caloric restriction-based strategies or periodic fasting have a favorable impact on health and longevity, both in non-human primates (Colman et al., 2009, Mattison et al., 2017) and in human studies (Longo and Mattson, 2014), although studies carried out in different research centers yielded controversial results regarding CR-mediated improved survival outcomes in rhesus monkeys (Mattison et al., 2012). CRMs have been efficiently used to sensitize tumor cells to chemotherapy (Pietrocola et al., 2016), to treat obesity and metabolic syndrome (Cantó et al., 2012), and to prolong health span and lifespan (Eisenberg et al., 2016, Eisenberg et al., 2017, Madeo et al., 2014). Aspirin is known to reduce the occurrence and progression of several human cancer types (Li et al., 2015, Rothwell et al., 2012), to reverse high-fat diet-induced insulin resistance (Kim et al., 2001), and to prolong lifespan in mice (Strong et al., 2008)."
 

Philomath

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I just made a post about fasting raising risk of early death by about 30%. On the other hand, fasting has been shown to lower biomarkers of inflammation as well as increase autophagy, with at least the former being undeniably beneficial. We already know from other studies that the benefits of fasting are largely due to lower levels of endotoxin (LPS) as well as restriction of intake of specific amino acids such as tryptophan, methionine, cysteine, arginine, glutamate, etc. Thus, if one were to eat food deficient in those nutrients while also keeping the microbiome in check with charcoal, insoluble fiber, antibiotics, etc then one would not need to restrict calories. However, keeping all these rules in mind can get pretty exhausting and invariably people slip on their dietary rules. So, instead of playing Russian roulette with fasting and hoping it won't lead to an early death, wouldn't it be be nice if one could get those benefits of fasting but without the risks, while also not restricting calories, specific nutrients, or worrying about the microbiome? The study below presents evidence that taking aspirin daily may be such an all-in-one caloric restriction mimetic (CRM). The daily HED of the mice dose the study experimented with was about 8mg/kg, which means that taking 2 tablets (325mg each) aspirin daily should be able to replicate for most people the design of this study.

Aspirin Recapitulates Features of Caloric Restriction - PubMed
"...Based on the results described in this paper, aspirin may be classified as a CRM. Indeed, aspirin fulfills all the criteria of a CRM (Madeo et al., 2014) as it (1) reduces protein acetylation by virtue of its ability to inhibit the acetyltransferase activity of EP300, (2) stimulates autophagic flux, and (3) has no cytotoxic activity. Caloric restriction-based strategies or periodic fasting have a favorable impact on health and longevity, both in non-human primates (Colman et al., 2009, Mattison et al., 2017) and in human studies (Longo and Mattson, 2014), although studies carried out in different research centers yielded controversial results regarding CR-mediated improved survival outcomes in rhesus monkeys (Mattison et al., 2012). CRMs have been efficiently used to sensitize tumor cells to chemotherapy (Pietrocola et al., 2016), to treat obesity and metabolic syndrome (Cantó et al., 2012), and to prolong health span and lifespan (Eisenberg et al., 2016, Eisenberg et al., 2017, Madeo et al., 2014). Aspirin is known to reduce the occurrence and progression of several human cancer types (Li et al., 2015, Rothwell et al., 2012), to reverse high-fat diet-induced insulin resistance (Kim et al., 2001), and to prolong lifespan in mice (Strong et al., 2008)."
Anecdotal, but I remember reading about a centenarian that said he took an Anacin every day. Anacin is an OTC pain reliever - each pill is about 800mg aspirin and 65mg caffeine
 
OP
haidut

haidut

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Anecdotal, but I remember reading about a centenarian that said he took an Anacin every day. Anacin is an OTC pain reliever - each pill is about 800mg aspirin and 65mg caffeine

Thanks.
Far from anecdotal, I would say. I think there are already studies with Anacin in animals, and both aspirin and caffeine have separately been shown to be remarkable life extenders.
 

DennisX

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Anecdotal, but I remember reading about a centenarian that said he took an Anacin every day. Anacin is an OTC pain reliever - each pill is about 800mg aspirin and 65mg caffeine
One Anacin tab is 400mg and 32mg caffeine on Amazon
 

Regina

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I just made a post about fasting raising risk of early death by about 30%. On the other hand, fasting has been shown to lower biomarkers of inflammation as well as increase autophagy, with at least the former being undeniably beneficial. We already know from other studies that the benefits of fasting are largely due to lower levels of endotoxin (LPS) as well as restriction of intake of specific amino acids such as tryptophan, methionine, cysteine, arginine, glutamate, etc. Thus, if one were to eat food deficient in those nutrients while also keeping the microbiome in check with charcoal, insoluble fiber, antibiotics, etc then one would not need to restrict calories. However, keeping all these rules in mind can get pretty exhausting and invariably people slip on their dietary rules. So, instead of playing Russian roulette with fasting and hoping it won't lead to an early death, wouldn't it be be nice if one could get those benefits of fasting but without the risks, while also not restricting calories, specific nutrients, or worrying about the microbiome? The study below presents evidence that taking aspirin daily may be such an all-in-one caloric restriction mimetic (CRM). The daily HED of the mice dose the study experimented with was about 8mg/kg, which means that taking 2 tablets (325mg each) aspirin daily should be able to replicate for most people the design of this study.

Aspirin Recapitulates Features of Caloric Restriction - PubMed
"...Based on the results described in this paper, aspirin may be classified as a CRM. Indeed, aspirin fulfills all the criteria of a CRM (Madeo et al., 2014) as it (1) reduces protein acetylation by virtue of its ability to inhibit the acetyltransferase activity of EP300, (2) stimulates autophagic flux, and (3) has no cytotoxic activity. Caloric restriction-based strategies or periodic fasting have a favorable impact on health and longevity, both in non-human primates (Colman et al., 2009, Mattison et al., 2017) and in human studies (Longo and Mattson, 2014), although studies carried out in different research centers yielded controversial results regarding CR-mediated improved survival outcomes in rhesus monkeys (Mattison et al., 2012). CRMs have been efficiently used to sensitize tumor cells to chemotherapy (Pietrocola et al., 2016), to treat obesity and metabolic syndrome (Cantó et al., 2012), and to prolong health span and lifespan (Eisenberg et al., 2016, Eisenberg et al., 2017, Madeo et al., 2014). Aspirin is known to reduce the occurrence and progression of several human cancer types (Li et al., 2015, Rothwell et al., 2012), to reverse high-fat diet-induced insulin resistance (Kim et al., 2001), and to prolong lifespan in mice (Strong et al., 2008)."
Great!
 

aliml

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Classification of protective substances as Caloric Restriction Mimetic, potential caloric restriction mimetic, and other compounds

GroupSubstance(Major) Molecular Target(s)
CRMsaspirin (and salicylate)AMPK, EP300, COX-1, COX-2, mTOR, NF-kB
hydroxycitric acidACLYdiverse tropical plants, Garcinia cambogia, and Hibiscus sabdariffa
resveratrolKDACs (SIRT1), AMPK, NF-κBfruits, plants, and skin of grapes
spermidineKATs (EP300), mTOR, AMPKwheat germs, soybeans, and nuts
Potential CRMs1,2,3-benzenetricarboxylatecitrate transport protein
acipimoxniacin receptor 1synthetic
berberineSIRT1Berberis vulgaris and several other plants (roots and bark)
caffeic acidAMPK and sirtuinseucalyptus bark
catechinpleiotropic, exact mechanism unknowncocoa, tea, and red wine
curcuminAMPK, mTOR, and EP300Curcuma longa
epicatechinpleiotropic, exact mechanism unknowncocoa, tea, and red wine
EGCGAMPK, mTOR, HATs, and KDACsgreen tea
gallic acidAMPK and HATsblack tea and various plants
metforminAMPK, mTOR, HATs, and KDACs (sirtuins)French lilac (Galega officinalis)
myricetinSIRT1black tea, cole, parsley, garlic, curcuma, and fruits
NAD+KDACs (sirtuins), AMPKvarious food
nicotinamideKDACs (sirtuins)various food
nicotinamide mononucleotideKDACs (sirtuins)various food
nicotinamide ribosideKDACs (sirtuins)various food
perhexiline maleatecarnitine O-palmitoyl transferase 1, mTORsynthetic
piceatannolSIRT1passion fruit seeds
quercetinSIRT1black tea, onions, rocket, cole, curcuma, and fruits
rapamycinmTORStreptomyces hygroscopicus
SRT1720SIRT1synthetic
UK5099mitochondrial pyruvate carriersynthetic
Others4,4′-dimethoxychalconeGATA transcription factors
A-485EP300synthetic
acarboseα-glucosidasebacterial (Streptomyces, Actinoplanes)
anacardic acidEP300cashew nutshell, Anacardium occidentale
C646EP300synthetic
CAEAAMPK, sirtuinssynthetic
CAPEAMPKpropolis
CPI-613pyruvate dehydrogenasesynthetic
garcinolEP300Garcinia indica
glucosaminehexokinase and mTORcrustaceans, cartilage
radicicolACLY and HSP90Monosporium bonorden
SRT501SIRT1see resveratrol
SB-204990ACLYsynthetic
SRT2104SIRT1synthetic

Summary of selected dietarily available compounds with Caloric Restriction Mimetic properties, their estimated intake levels, food sources, and comprehensive literature reviews

Class
Compound
Estimated dietary intake levels#+
Relevant dietary sources+
Glycolysis inhibitors​
Astragalin (glucoside form of kaempferol; also a polyphenol)​
Unknown​
Various plants, including Astragalus, Cuscuta (dodder), Cassia alata
D-Allulose (D-psicose)​
Unknown​
Wheat, Itea, processed cane and beet molasses, high-sugar products (e.g., seasoning sauces, especially after heating)​
Chrysin (5,7-dihydroxyflavone; also a polyphenol)​
Unknown​
Honey, propolis, passion flowers, mushrooms​
Genistein (4′,5,7-trihydroxyisoflavone; also a polyphenol)​
2–50 mg/day (total isoflavones of which genistein is a major type)​
Various foods, soy-based items, legumes, fruits, nuts, vegetables​
D-Glucosamine​
Unknown​
Shellfish shells, cartilage, fungi​
Mannoheptulose​
Unknown​
Unripe avocados​
Di/Polyamines​
Putrescine, spermidine, spermine​
3–18 mg/day​
Various plant and animal-based foods, soy beans, cheese, nuts, seeds, wheat germs​
Polyphenols​
Total polyphenols​
1 g/day​
Various​
3,4′-dimethoxychalcone​
Unknown​
*Unknown​
4,4′-dimethoxychalcone​
Unknown​
*Angelica keiskei (ashitaba)​
Curcumin​
29.4 mg/day​
Curcuma longa​
Flavan-3-ols (e.g., epicatechin, EGCG)​
23–384 mg/day​
Green tea, apples, pears, berries, cocoa, broad beans​
Gallic acid​
25 mg/day​
Berries, citrus fruits, leaf vegetables, soy products, tea​
Isobacachalcone​
Unknown​
*Angelica keiskei (ashitaba), Artocarpus sp. (breadfruit), Erythrina fusca (purple coraltree), Morus alba (white mulberry), Piper longum (long pepper)​
Quercetin​
13.5–29.4 mg/day​
Onions, apples, berries​
Resveratrol​
0.1–8 mg/day​
Wines, grapes, lingonberry and >100 other plants​
Others​
Hydroxycitric acid (HCA)​
Unknown​
Garcinia and Hibiscus​
Salicylic acid​
1.3–4.4 mg/day​
Berries, (citrus) fruits, fruit juices, wines, vegetables (asparagus, onions)​
NAD+​
21.9–41 niacin equivalents (mg)/day​
Various plant and animal-based foods, peanuts, nuts, tuna, fish, pork, beef, soy beans, cheese, wheat germs​

CO2 is another caloric restriction mimetic!
 

Philomath

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JohnHafterson

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Anecdotal, but I remember reading about a centenarian that said he took an Anacin every day. Anacin is an OTC pain reliever - each pill is about 800mg aspirin and 65mg caffeine
Good combo caffeine + aspirin:

 

Nik665

Member
Joined
Sep 3, 2020
Messages
265
I just made a post about fasting raising risk of early death by about 30%. On the other hand, fasting has been shown to lower biomarkers of inflammation as well as increase autophagy, with at least the former being undeniably beneficial. We already know from other studies that the benefits of fasting are largely due to lower levels of endotoxin (LPS) as well as restriction of intake of specific amino acids such as tryptophan, methionine, cysteine, arginine, glutamate, etc. Thus, if one were to eat food deficient in those nutrients while also keeping the microbiome in check with charcoal, insoluble fiber, antibiotics, etc then one would not need to restrict calories. However, keeping all these rules in mind can get pretty exhausting and invariably people slip on their dietary rules. So, instead of playing Russian roulette with fasting and hoping it won't lead to an early death, wouldn't it be be nice if one could get those benefits of fasting but without the risks, while also not restricting calories, specific nutrients, or worrying about the microbiome? The study below presents evidence that taking aspirin daily may be such an all-in-one caloric restriction mimetic (CRM). The daily HED of the mice dose the study experimented with was about 8mg/kg, which means that taking 2 tablets (325mg each) aspirin daily should be able to replicate for most people the design of this study.

Aspirin Recapitulates Features of Caloric Restriction - PubMed
"...Based on the results described in this paper, aspirin may be classified as a CRM. Indeed, aspirin fulfills all the criteria of a CRM (Madeo et al., 2014) as it (1) reduces protein acetylation by virtue of its ability to inhibit the acetyltransferase activity of EP300, (2) stimulates autophagic flux, and (3) has no cytotoxic activity. Caloric restriction-based strategies or periodic fasting have a favorable impact on health and longevity, both in non-human primates (Colman et al., 2009, Mattison et al., 2017) and in human studies (Longo and Mattson, 2014), although studies carried out in different research centers yielded controversial results regarding CR-mediated improved survival outcomes in rhesus monkeys (Mattison et al., 2012). CRMs have been efficiently used to sensitize tumor cells to chemotherapy (Pietrocola et al., 2016), to treat obesity and metabolic syndrome (Cantó et al., 2012), and to prolong health span and lifespan (Eisenberg et al., 2016, Eisenberg et al., 2017, Madeo et al., 2014). Aspirin is known to reduce the occurrence and progression of several human cancer types (Li et al., 2015, Rothwell et al., 2012), to reverse high-fat diet-induced insulin resistance (Kim et al., 2001), and to prolong lifespan in mice (Strong et al., 2008)."
So you just said and quested calorie restriction showd to be beneficial in humans per Valter longos study so why not just do a low calorie diet 5 days a year like Longo recommends lnstesd of taking a bunch of supplements???
 

ddjd

Member
Joined
Jul 13, 2014
Messages
6,864
Classification of protective substances as Caloric Restriction Mimetic, potential caloric restriction mimetic, and other compounds

GroupSubstance(Major) Molecular Target(s)
CRMsaspirin (and salicylate)AMPK, EP300, COX-1, COX-2, mTOR, NF-kB
hydroxycitric acidACLYdiverse tropical plants, Garcinia cambogia, and Hibiscus sabdariffa
resveratrolKDACs (SIRT1), AMPK, NF-κBfruits, plants, and skin of grapes
spermidineKATs (EP300), mTOR, AMPKwheat germs, soybeans, and nuts
Potential CRMs1,2,3-benzenetricarboxylatecitrate transport protein
acipimoxniacin receptor 1synthetic
berberineSIRT1Berberis vulgaris and several other plants (roots and bark)
caffeic acidAMPK and sirtuinseucalyptus bark
catechinpleiotropic, exact mechanism unknowncocoa, tea, and red wine
curcuminAMPK, mTOR, and EP300Curcuma longa
epicatechinpleiotropic, exact mechanism unknowncocoa, tea, and red wine
EGCGAMPK, mTOR, HATs, and KDACsgreen tea
gallic acidAMPK and HATsblack tea and various plants
metforminAMPK, mTOR, HATs, and KDACs (sirtuins)French lilac (Galega officinalis)
myricetinSIRT1black tea, cole, parsley, garlic, curcuma, and fruits
NAD+KDACs (sirtuins), AMPKvarious food
nicotinamideKDACs (sirtuins)various food
nicotinamide mononucleotideKDACs (sirtuins)various food
nicotinamide ribosideKDACs (sirtuins)various food
perhexiline maleatecarnitine O-palmitoyl transferase 1, mTORsynthetic
piceatannolSIRT1passion fruit seeds
quercetinSIRT1black tea, onions, rocket, cole, curcuma, and fruits
rapamycinmTORStreptomyces hygroscopicus
SRT1720SIRT1synthetic
UK5099mitochondrial pyruvate carriersynthetic
Others4,4′-dimethoxychalconeGATA transcription factors
A-485EP300synthetic
acarboseα-glucosidasebacterial (Streptomyces, Actinoplanes)
anacardic acidEP300cashew nutshell, Anacardium occidentale
C646EP300synthetic
CAEAAMPK, sirtuinssynthetic
CAPEAMPKpropolis
CPI-613pyruvate dehydrogenasesynthetic
garcinolEP300Garcinia indica
glucosaminehexokinase and mTORcrustaceans, cartilage
radicicolACLY and HSP90Monosporium bonorden
SRT501SIRT1see resveratrol
SB-204990ACLYsynthetic
SRT2104SIRT1synthetic

Summary of selected dietarily available compounds with Caloric Restriction Mimetic properties, their estimated intake levels, food sources, and comprehensive literature reviews

Class
Compound
Estimated dietary intake levels#+
Relevant dietary sources+
Glycolysis inhibitors​
Astragalin (glucoside form of kaempferol; also a polyphenol)​
Unknown​
Various plants, including Astragalus, Cuscuta (dodder), Cassia alata
D-Allulose (D-psicose)​
Unknown​
Wheat, Itea, processed cane and beet molasses, high-sugar products (e.g., seasoning sauces, especially after heating)​
Chrysin (5,7-dihydroxyflavone; also a polyphenol)​
Unknown​
Honey, propolis, passion flowers, mushrooms​
Genistein (4′,5,7-trihydroxyisoflavone; also a polyphenol)​
2–50 mg/day (total isoflavones of which genistein is a major type)​
Various foods, soy-based items, legumes, fruits, nuts, vegetables​
D-Glucosamine​
Unknown​
Shellfish shells, cartilage, fungi​
Mannoheptulose​
Unknown​
Unripe avocados​
Di/Polyamines​
Putrescine, spermidine, spermine​
3–18 mg/day​
Various plant and animal-based foods, soy beans, cheese, nuts, seeds, wheat germs​
Polyphenols​
Total polyphenols​
1 g/day​
Various​
3,4′-dimethoxychalcone​
Unknown​
*Unknown​
4,4′-dimethoxychalcone​
Unknown​
*Angelica keiskei (ashitaba)​
Curcumin​
29.4 mg/day​
Curcuma longa​
Flavan-3-ols (e.g., epicatechin, EGCG)​
23–384 mg/day​
Green tea, apples, pears, berries, cocoa, broad beans​
Gallic acid​
25 mg/day​
Berries, citrus fruits, leaf vegetables, soy products, tea​
Isobacachalcone​
Unknown​
*Angelica keiskei (ashitaba), Artocarpus sp. (breadfruit), Erythrina fusca (purple coraltree), Morus alba (white mulberry), Piper longum (long pepper)​
Quercetin​
13.5–29.4 mg/day​
Onions, apples, berries​
Resveratrol​
0.1–8 mg/day​
Wines, grapes, lingonberry and >100 other plants​
Others​
Hydroxycitric acid (HCA)​
Unknown​
Garcinia and Hibiscus​
Salicylic acid​
1.3–4.4 mg/day​
Berries, (citrus) fruits, fruit juices, wines, vegetables (asparagus, onions)​
NAD+​
21.9–41 niacin equivalents (mg)/day​
Various plant and animal-based foods, peanuts, nuts, tuna, fish, pork, beef, soy beans, cheese, wheat germs​

CO2 is another caloric restriction mimetic!

View: https://twitter.com/drtaubraun/status/1680180519604985856?t=2AV1RkGsUkNafjRM_bdpHw&s=19
 

DrJ

Member
Joined
Jun 16, 2015
Messages
726
Not mentioned in the OP is that fasting allows insulin to drop and stay low and thus would ameliorate the problems associated with hyperinsulinemia during a fast.
 
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