I think such a list with resources would be nice to have, at least for optimizing our stacks and lifestyles to better serve our goals.
Interventions for longevity:
1) Intermittent mTOR inhibition
(for Increased Autophagy, reducing hyperfunction, reducing SASP)
- this would include fasting, IF, FMD, low protein diets, calorie restriction, metformin (via AMPK activation), berberine (via AMPK activation)
- retinol for skin also works through mTOR inhibition
2) AMPK activation:
(for Increased Autophagy, reducing hyperfunction, and reducing insulin resistance)
-
fasting, calorie restriction
-
metformin, - berberine
– Important potential side effects: reduces benefits of exercise, hypoglycemia and ketoacidosis especially in diabetics, mitochondrial poisoning (?)
3) Alphaglucosidase inhibitors which reduce/slow down the digestion of starch
(for healthy blood sugar/insulin levels)
- Acarbose
- White Kidney bean extract, …
- Allulose to a small extent (?)
Potential side effects to be mindful of: bloating, gastrointestinal issues
Other ways to to reduce/slow down digestion of starch
(for healthy blood sugar/insulin levels)
- consuming fiber and proteins prior to carbs
- Apple cider vinegar?
- lean towards resistant starches (?)
- consume less starch
(4) SGLT-2 inhibitors lowers blood glucose peaks
They excrete excess blood glucose via the kidney:
(for healthy blood sugar/insulin levels)
Sugar Substitutes:
Important potential side effects: fatigue, UTI
5) 17-alpha estradiol
6) Ca-alpha ketoglutarate
- Arginine alphaketoglutarate may act very similarly
Note: Saw this on the GRG email discussion forum:
"…, but the best is calcium AAKG specifically, rather than L-ornithine or L-arginine or any other forms.
I had a discussion about this last year with Dr Dan Stickler of the Apeiron Center for Human Potential when I asked him why Rejuvant used the calcium form, and this was his reply:
"So I received the answer regarding the forms of AKG: Free-form AKG is rapidly metabolized in oral form, this occurs with the chelated forms (l-arginine and ornithine). Salts tend to slow absorption. Calcium performed much better than Na in the trials but then the calcium form was further modified to create sustained release which is what they suspect is responsible for the beneficial effect of the SR ca-AKG that they have found in the studies. "
7) Senolytics:
(via selectively killing senescent cells)
- Dasatinib + Quercetin OR Dasatinib + Fisetin
- Piperlongumine (from long-pepper)
- Procyanidin-C1 (PCC-1) present in grapeseed extract, apple polyphenols, etc.
- Gingerone-A present in ginger extract
- Curcumin (?),
- quercetin (in combination with others at least)
- Azithromycin
- Navitoclax
- strength training (w.r.t skeletal muscles)
Important potential side effects: delayed wound healing, killing of non-senescent cells, chronic users of dasatinib had memory impairments. Risk-reward ratio may be tissue-specific.
More pathways with potential, because they tend to broadly improve health:
8) GLP-1 analogues/agonists:
(for weight loss and maintaining healthy blood sugar/insulin levels, eliminating visceral fat, NAFLD, etc. May have fewer benefits in those already at ideal body composition and with no metabolic health issues. )
- Semaglutide, liraglutide
- also seen to some extent in Gymema sylvestre, Yerba Mate, Guayusa tea
9) Fructokinase inhibition – luteolin
10) NRF-2 activators:
11) Iron reduction
(developing field w.r.t. understanding mechanisms)
- blood donation, phlebotomy, iron chelation, sauna use (?)
–Optimal ferritin levels (25-100 μg/ml ?)
–Important potential side effects: anemia if driven too low
12) Prevent inflammaging:
- Fish oil, senolytics, rapamycin, …
13) Exogenous ketones (BHB salts, ketone esters), MCT Oil, ketogenic diet, fasting, have the benefit of both reducing insulin / blood glucose levels as well benefiting from ketone metabolism, improving satiety, etc. There may be other unique aspects that exgenous ketones may bring into play as well The Buck Institute Launches First Human Clinical Trial
14) Exercise:
- Zone-2 exercise for improved mitochondrial function, improved cardiovascular benefits
- HIIT or zone-4/zone-5 exercise to improve lactate metabolism (?), and efficiently reduce visceral fat. Note higher chance of injuries here.
- Zone-1 or just walking a lot is shown to help
- Zone-3 can provide cardiovascular benefits
- Strength training in addition to improving metabolic rate, and lean muscle mass can reduce senescent cells in the skeletal muscles
15) Reduce stress
- meditation, psychotherapy for improving stress reslience
- ashwagandha, CBD (?), L-ornithine, Phosphatidylserine (?), to reduce cortisol levels
16) Taking care of common deficiencies:
- Vitamin B12, Vitamin D, Magnesium, Creatine,
17) NAD Precursors - NMN / NR-- I’m not very convinced of this yet, but seems safe. Topical nicotinamide seems to help with skin aging
Cheaper options for NAD Precursors:
- Nicotinimide
- Niacin
- Niacinimide
18) Hormetic Stress Inducers - see this video
- Sauna
- Cold Water / Ice bath
19) Higher Fiber Intake / Microbiome Optimization - see this video by Mike Lustgarten on High Fiber Benefits
Benefits of Oligo-fructose enriched Inulin (all inulin seems to have this) - see This video by Mike Lustgarten.
20) Reducing the accumulation of sphingolipids (a new/tentative hallmark of aging based on mice data)-
Myriocin (for inhibition of ceramide synthesis) https://scitechdaily.com/researchers-identify-a-new-hallmark-of-aging/
perhaps more relevant for older than younger folks.
21) Improve vascular health - PDE5 inhibitors (cialis, sildefanil), sauna, exercise, cocoa
Chocolate (dark) decreases all-cause mortality - See video by Mike Lustgarten
22) Eliminate ‘forever chemicals’( Per- and polyfluoroalkyl substances (PFASs))
Plasma donation is most helpful as this can be done often.
But blood donation also helps.
Get RO water.
23) Microdosing Lithium – works via hormesis OR other currently unknown mechanisms
24) Urolithin-A: promotes mitophagy through the gut microbiome. Exercise, fasting, rapamycin, etc. also contribute to mitophagy.
TODO (understand how this relates with mitofusion – e.g. strearic acid is useful there)
25) Plasma dilution – See Irina Conboy’s work.
It’s likely that plasma donation produces similar benefits.
26) Reduce risk of Artherosclerosis/ Cardivascular disease:
Avoid excess saturated fat, statins, pcsk9 inhibitors, ezetimibe, exercise, sglt2i
-
Avoid air pollution: air purifiers, n95 masks
Other supplement recommendations:
The Kaufman Protocol (cell biologist who also focuses on anti-aging - [her website],(https://kaufmannprotocol.com), Interview with her on her recommended supplements.
- Pterostilbene,
- Astaxanthin,
- Nicotinamide,
- Carnosine,
- Curcumin
- Quercetin,
- Lactoferrin
- Spermidine
Habits / Outcomes to avoid:
(a) drinking fructose
(b) drinking alcohol
- American oncology association and many papers show increased risk of cancer at any dosage
- at very low doses (a glass at 0.5% concentration ?), it can however have positive benefits by downregulating mTOR
(c) chronically,
- high blood glucose / inuslin levels
- high inflammation
- being stressed
- restricting mTOR
– can lead to depression, reduce immunity against communicable diseases
- upregulating mTOR (hyperfunction theory of aging)
– increases stem cell size, reduces autophagy, may support growth of cancer cells
(c) sedentary lifestyle
(d) smoking, air pollution
(e) developing visceral fat, fatty liver, fatty pancreas, insulin resistance
I’ll need to keep revisiting this to clean up the text, add references, nuances, dosages, etc.
But please comment if you have any thoughts.
Possible Additions (Add your own below)
Chat below so far contains
1) Hyperbaric Oxygen Therapy (HBOT)
2) Currently experimental compounds J147
