Anti-aging strategies and the ways to implement them

Supplements
#1

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

  1. 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

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Can you share your Longevity / HealthSpan Regime?
Are there supplements that enhance Rapamycin?
#2

Great idea. Let me pull my list together… and I assume you saw this, more broadly than just mimetic:

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#3

Yep, I’ve seen that post by Blagosklonny! And to be more precise, I was going for something like that, but also with a list of potential agents that would fit a particular strategy (natural or otherwise).

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#4

Thanks for the summary

Let me add another intervention to the list:
Hyperbaric oxygen treatments increase 38% length of the telomeres, and decrease 37% senescent cells

But Hyperbaric oxygen treatment is expensive and with risks
In the following video, Steve Buss suggests EWOT(Exercising with Oxygen Therapy) may be one of the most powerful rejuvenation regimens, by inducing similar mechanisms observed in the Hyperbaric oxygen treatments study
Video starts at 1h4m17s

For EWOT equipment, Steve Buss mentioned two company

  • Optimalbreathing
  • Liveo2

And here is a video of how to diy EWOT System (for the oxygen reservoir bag)

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#5

AlexK has a good list here:

Oooo… and I just found this - great stuff! is it being updated and maintained? @AlexKChen

https://longevitybase.org

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#6

Great summary, thanks for sharing.

In terms of evidence based, I completely agree with your list though, I’m quite fascinated with SKQ-1 despite the evidence of beneficial ROS which I couldn’t debate the beneficial evident literature. I have lupus and based on my personal experimenting, it has profound subjective benefits in myself such as increased energy, cognitive function, muscle mass/ function, stronger. In terms of biomarkers, I believe it increased my IGF-1 levels from 220ng/ml to 345ng/ml within 5 months time with a dosing regime of 5mg bid.

Again, another research compound- J-147 which the subjective brain effects are simply life changing.

These two compounds have improved my quality of life over any other such as, canagliflozin, metformin, acarbose, semaglutide, NMM, senolytics. Only compound that felt close, subjectively was rapamycin.

At this time, I’m most interested in experimenting with 17-a estradiol.

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#7

Yes - I think that is the next big compound that people more in the biohacker end of the spectrum might be trying starting… well, probably now.

There have been human clinical safety trials and it seems fine at least in the short term. Its already part of the standard estradiol that millions of women take each year (they don’t separate the alpha and the beta that is in the standard estradiol sold today by the millions) - so again, its well established and used in humans already.

And - its already relatively easily available (if you have a friend who works in a chemistry or biology department of a university, etc.) and its cheap. If anyone out there is using it - please post a note on how the personal trial is going.

More data here:

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#8

Incidentally - on J-147, have you seen any published research on it since 2015? The fact that someone has filed an IND (Investigational new drug) with the FDA on it, but then nothing has happened in the past 7 years in terms of research, suggests to me that some kind of problem probably came up and that its been abandoned as a drug candidate. Would you agree?

#9

It’s possible, though in my opinion not probable. I’ve contacted them on the topic as it’s a good question, I’m curious of development as well. I’ve followed development but not as close as I should be.

2018-

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#10

AMPK (activation) not “inhibition”- typo.

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#11

Is it the view of longevity researchers that CBD has no significant merit? There seems to be some interesting research on the internet.

#12

I’ve never seen any longevity research on CBD - can you share some?

#13

I’ve made 10 edits to the post already. Doesn’t look like it allows me to make more edits :confused:

#14

OK - I made that post into a “wiki” that anyone can edit now and add too. Let me know if there are any issues - this is my first time using this feature.

At the bottom of the first post is an “Edit” button - just click on that to change things.

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#15

A recent paper on HBOT and insulin sensitivity: Hyperbaric oxygen rapidly improves tissue-specific insulin sensitivity and mitochondrial capacity in humans with type 2 diabetes: a randomised placebo-controlled crossover trial - Diabetologia

#16

Do you have any personal experience with HBOT? I’m looking up literature to see if it also has benefits for otherwise healthy individuals.

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#17

Actually in a normal or lower weight person (controlling total calories), higher carbohydrate to fat ratio is more life extending.

Keto seems to leak into niches where it has zero benefits because a lot of people are fat nowadays and have insulin problems people think the less carbs the better. Sure hormone levels may benefit from fats and there may be more protection against insulin issues but those are short term benefits, not for the upper percentiles of life-extension.

I do agree with the usage of some of mentioned above supplements, and to continue improving our knowledge on anti-aging compounds.

#18

My thinking about keto has evolved too.

I currently think about carbs making more sense around exercise, especially HIIT or resistance training.
i) it could be less harmful, because any energy would be prioritized by muscles during exercise rather than the liver
ii) it could even be beneficial by promoting hypertrophy of muscles, allowing for more HIIT, etc.

But that said, I try to be in keto as a default. The ITP results w.r.t canagliflozin, acarbose which lowers glucose spikes, and with rapamycin (which is also activated by insulin), make me lean more towards keto than away from it. I know that triglycerides/ LDL-C levels can be an issue with keto, so I’m also very liberal with fibre and try to use more monounsaturated fat (and stearic acid), and I think that’s working out well so far, but I’ll know better when I get my blood work done again.

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#19

See TED talk of Shai Efrati below.

They have a branch somewhere in Florida. It, does look expensive.

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#20

How do you supplement for # 20 myriocin?