Aging is not one thing, there are many hallmarks. So re-youthing will require a combination of therapies.

Hallmark	How to fix	*Possible Interventions
Epigenetic decoherence	increase global methylation decrease methylation at specific CGI's histone modification (via sirtuins and histone deacetylases and miRNAs), chromatin remodeling reset via reprogramming factors	Exercise, rapamycin, astragalus, glutathione EGCG, Compound H N-(2-chlorophenyl)-1H-indole-3-carboxamide (demethylizes promoter at KLOTHO site) Lunasin, Pterostilbene/resveratrol, ALA, 4-(pyridin-3-yl)-4,5-dihydropyrrolo[1,2-a]quinoxaline, NMN, NR, Beta-Lapachone, NAD+, garlic AAV transfection of OSK factors (not commercially avail)
Genomic instability	Boost DNA repair/protection mechanisms Boost suicide of damaged(apoptosis) inhibit Transposable Elements (transposons)	Fasting, exercise, sleep, JNK activator: GnRH ; SIRT6 activators: Cyanidin, Pioglitazone, 4-(pyridin-3-yl)-4,5-dihydropyrrolo[1,2-a]quinoxaline, Luteolin, quercetin, Vit D, folate, curcumin, astaxanthin, Pterostilbene, NMN, NR, NAD+ Fasting, Beta-Lapachone, salicylate, aspirin(any NSAID) Icariin, lamivudine(but toxic), Capsaicin(but toxic), Pterostilbene, 4-(pyridin-3-yl)-4,5-dihydropyrrolo[1,2-a]quinoxaline, NMN, NR, NAD+
Telomere attrition	promote telomerase inhibit cell-cycle anti-apoptotic reset via reprogramming factors	cycloastraganol(astragalus extract), carnosine(with Beta-Alanine), apigenin, HRT, danogen rapamycin, tamoxifen metformin, Hot/Cold therapy, humanin, tauroursodeoxycholic acid (TUDCA) AAV transfection of OSK factors (not commercially avail)
Cellular senescence	kill senescent cells lower SASPs	Fisetin, Dasatinib+Quercetin(fat & epithelial), Azithromycin(lung){metformin contraindicated}, Roxithromycin(skin), navitoclax(blood), FOX04-dri Rapamycin, apigenin, exosomes, metformin
Mitochondrial dysfunction	quench ROS at mito membrane Boost mDNA repair/protection mechanisms increase number of copies of mtDNA Boost suicide of damaged(mitophagy) Membrane Lipid replacement	C60 Oil, MitoQ, Deprenyl, glutathione, CoQ10, DMF Fasting, exercise, Humanin (or even better HNG), mots-c, Nilotinib, NMN, NR, NAD+ Lipid nanoparticles (negatively charged with fusogenic protein) encapsulating mtDNA, PQQ urolithin A(Pomegranate extract), Stearic acid Stearic acid, Phosphatidylcholine
Stem cell exhaustion	replace stimulate stem cell self-renewal improve niche	Allogeneic Stem Cell Transplant (but only tiny percentage engraft) Stearic acid, spirulina, fucoidan, aphanizomenon flos-aquae, ginko biloba, JQ1, NHLRC3/royalactin, fasting(refeeding), CASIN( 2-[(2,3,4,9-Tetrahydro-6-phenyl-1H-carbazol-1-yl)amino]ethanol ), oxytocin Exosomes, Allogeneic Stem Cell Transplant, prp, Anti-inflammatories, HRT, GDF11
Loss of proteostasis	decrease protein misfolding boost autophagy, lysosomes AGE breakers AGE inhibitors	Fasting, Pterostilbene, sulforaphane, EGCG (green tea), Selumetinib, cocoa extract Fasting, BHB, Pterostilbene, Rapamycin, trehalose, benfotiamine, Genistein, lithium, spermidine, probiotics, wheatgerm, Honokiol, taurine, curcumin N-Acetyl-L-Carnosine, Chebulic acid, ALT-711, rMnP, Minodronate Carnosine, aminoguanidine, metformin, acarbose, pyridoxamine, glucosamine, EDTA, BHT
Deregulated nutrient sensing	regulate IGF-1 decrease mTOR increase sirtuins(especially SIRT1, 3, and 6) increase AMPK	Fasting, avoid sugar/simple carbs, cycle BHB Rapamycin, metformin(take with folate and taurine), acarbose SRT1720, SRT2104, Pterostilbene/resveratrol, NMN, Metformin Jiaogulan, Humanin, mots-c, Metformin, berberine, glucosamine, rosehip
Altered intercellular communication	Signaling molecules Lower inflammation fight immunosenescence	Exosomes, DHEA, HRT (balance all hormones) Exosomes, glucosamine, Omega 3, curcumin, sulforaphane, aspirin, Andrographolide HRT, cistanche, probiotics, zinc, donate blood(removes some of the built-up deleterious factors, and crowded specialized immune cells), stimulate immune system(TLR5) using flagellin peptide
*This is for informational purposes only. Use at own risk. Many of the listed substances are based on rodent studies have not been tested on human subjects and are not FDA approved.
BuckyLabs is looking for good people in our quest to combat aging. So, please talk to us if you are interested in partnering in some way, we are especially interested in passionate folks with chemistry/biologics backgrounds.

**Example Longevity Regimen

	Day	Morning	Noon	Afternoon/Evening	Bedtime
	0	Get baseline bioage- battery of health tests and blood markers including your mDNA age.
	1	Donate (whole)blood, Start water fast	HIIT exercise, 20min sauna, cold shower	metformin(with B12 & folate), HRT-balance all hormones(include Vit D, GDF11) to youthful levels	melatonin, probiotic, aspirin
	2		BHB	metformin(with B12 & folate), HRT-balance all hormones(include Vit D, GDF11) to youthful levels	melatonin, aspirin, NAC
	3	HIIT exercise, 20min sauna, cold shower	BHB	HRT-balance all hormones(include Vit D, GDF11) to youthful levels	melatonin, aspirin
	4		Senolytic therapy: D+Q, fox04-dri	HRT-balance all hormones to youthful levels	melatonin, aspirin, NAC
	5	end fast -refeed (no sugar or simple carbs), Exosomes injection, metformin(with methyl folate), C60 olive oil, NMN/NR, pterostilbene	HIIT exercise, 20min sauna, cold shower. TUDCA, Pomegranate extract, Stearic acid, Phosphatidylcholine, liposomal C, garlic	metformin(with methyl folate), HRT-balance all hormones(include Vit D, GDF11) to youthful levels	melatonin, probiotic, aspirin
	6	C60 olive oil, NMN/NR, pterostilbene, glucosamine, Omega 3	Pomegranate extract, rapamycin, Icariin, carnosine	metformin(with methyl folate), HRT-balance all hormones to youthful levels	melatonin, aspirin, NAC
	7	C60 olive oil, NMN/NR, pterostilbene, glucosamine, Omega 3	apigenin, HIIT exercise, 20min sauna, cold shower	metformin(with B12 & folate), HRT-balance all hormones(include Vit D, GDF11) to youthful levels	melatonin, probiotic, aspirin
	8	C60 olive oil, NMN/NR, pterostilbene, glucosamine, Omega 3	TUDCA, Pomegranate extract, Stearic acid, Phosphatidylcholine, liposomal C, garlic, cycloastraganol	metformin(with B12 & folate), HRT-balance all hormones(include Vit D, GDF11) to youthful levels	melatonin, aspirin, NAC
	9	C60 olive oil, NMN/NR, pterostilbene, glucosamine, Omega 3	TUDCA, Pomegranate extract, Stearic acid, Phosphatidylcholine, liposomal C, garlic, cycloastraganol	metformin(with B12 & folate), HRT-balance all hormones(include Vit D, GDF11) to youthful levels	melatonin, probiotic, aspirin
	10	C60 olive oil, NMN/NR, pterostilbene, glucosamine, Omega 3	TUDCA, Pomegranate extract, Stearic acid, Phosphatidylcholine, liposomal C, garlic, cycloastraganol	metformin(with B12 & folate), HRT-balance all hormones(include Vit D, GDF11) to youthful levels	melatonin, aspirin, NAC
	…	…	…	…	…
		Get ending bioage- A battery of health tests and blood markers including your mDNA age.
**Talk to your doctor before starting any kind of radical protocol like this. Use at own risk.
This is based on many assumptions and largely on rodent studies (often interventions do not translate).

Optimizing a longevity protocol is complicated: Metformin depletes vitamin B12 and folate and this will raise homocysteine (there’s a debate whether homocysteine is directly harmful, or it is just a marker). So, metformin should be taken with Methylcobalamin(B12) and 6S-5-Methyltetrahydrofolate (a bioavailable version of folate). Metformin also lowers blood glucose, so it should help a person reach a state of ketosis (which can be further sped by taking BHB). But combining fasting with metformin could be dangerous, depending on the person (and a person with kidney problems can get lactic acidosis), and lead to hypoglycemia. Further, mixing High Intensity Interval training (HIIT) with fasting and metformin may hasten hypoglycemia. Metformin may also lower the effectiveness of exercise. Metformin also 'lowers the bar' for cells with damaged DNA to become senescent (which we would want to then kill with senolytics). Senolytics, theoretically, could be enhanced by being in a fasted/catabolic state. Shortly after a fast and a senolytic treatment would be an ideal time for hGH, exosomes (or a stem cell treatment).