The ultimate longevity guide: Live better for longer!

Most of us would like to live longer, so long as we have happy and healthy lives. Luckily, there are things we can do today, with our current knowledge and technology, to extend our lifespans. While there is a large genetic component to longevity, here at Hapi we think meaningful life extension can be achieved through the alteration of environmental factors such as lifestyle and therapy.

Below are some simple tips that could help you improve the quality of your life and live longer!

1. Lifestyle

Stop bad habits — stop smoking tobacco, if you can’t then switch from smoking to vaping; don’t drink more than one standard drink per day, and stop over-consuming recreational drugs.

Lose the excess weight, try to get below 23% body fat. Do this by finding a hunger suppressing diet-lifestyle you can maintain indefinitely, whether it’s high carb or low carb diet, an elimination or highly varied diet — stick with whatever works for you. One thing everyone should do is eat a little seafood every day… fish oil does not confer the same benefits as seafood — so unless you’re allergic, perhaps an easy habit is a small can of oysters each day?

Do long fasts, to clean up malfunctioning cells and repair DNA. For example you could fast 3–5 consecutive days… it takes a while for autophagy to kick in. As long as you keep a reasonable body weight, the more frequently you are able to fast, the better.

Exercise has broad and profound effects on health and longevity. If you don’t know where to start, a time-efficient form of exercise is high intensity interval training, and dancing, martial arts and team sports are usually rated more fun than plain cardio. If you’re too busy for exercise, do you really not have time — or do you simply not prioritize it?

Keep a strong circadian rhythm… a dysfunctional rhythm literally kills! Get lots of bright light and eat a large carb-protein breakfast as soon as you wake up, at least a few days per week to align your clock — this may not apply to a ketogenic diet, which naturally advances the circadian phase. Eat dinner 3–4 hours before bed. Take a little melatonin, and make your nights as dark as practical — don’t leave bright house lights on after 8pm, use red-LED lights instead, or use blue blocking goggles and rubylith films to block blue light.

Buffer your energy production with H2-water. This is as easy as putting a pure magnesium rod and some lemon in your drinking water! Keep hydrated — remember if you are feeling thirsty, or your urine is dark yellow, then you’re already dehydrated.

The Damage of Aging

The next section covers categories of problems that occur in the aging process — but don’t think they are exclusive — there’s a lot of interaction between all of these categories, they affect each other a lot.

2. Methylation

Methylation is a way of talking about how the programming code in our cells is expressed. Even if we have great code, if the body isn’t reading and writing it properly then the body cannot make proteins properly and we see increases in risk of disease.

As we age, there is a frustrating global hypomethylation contrasted by site-specific hypermethylation. Basically, most tissues under do it and some tissues really over do it. When tissues under-methylate we see an age-related underperformance, and when they over-methylate we worry about risk of cancer growth! How can we keep methylation running smoothly?

• Consume sufficient B12, B6 and folate and other B vitamins.
• Increase betaine and choline (leafy greens, beets and egg yolks).
• Minimise methionine intake (animal and soy protein).

If supplementing B-vitamins, is recommended to take a balanced multi-B rather than specific vitamins, unless there’s a medical reason to not do so.

3. Oxidation

Reactive oxygen species can damage both mitochondrial and cellular DNA, and induce epigenetic and metabolic changes. As we age, there is an accumulation of these damages. We want to induce hormesis and restore endogenous antioxidants like glutathione and buffer the antioxidant system so all of these reactive species are mopped up. We can also reduce our body’s output of reactive species.

• Eat more phytonutrients (lots of colorful fruit, veg, nuts, seeds).
• Eat more organic sulfur (lots of cruciferous plants like broccoli and cauliflower).
• Minimize methionine intake (animal and soy protein).
• Get a portion of energy from ketones (periodic dietary ketosis, or eat medium chain triglycerides).

4. Glycation

Over time, sugars in our blood will haphazardly bind to proteins and fats, leading to advanced glycation endproducts (AGEs). The accumulation of junk within and around cells is a major cause of aging — when enough of these damaged molecules accumulate the body starts to dysfunction. We can either prevent the production of AGEs inside the body, prevent the intake of AGEs from the environment, or increase their clearance from the body.

• Blood sugar control.
• Berberine and/or anthocyanidins (PBE).
• Slow and/or low carb diet.
• Eat high flavanoid foods (unprocessed plant foods).
• Avoid high-fructose processed and artificial foods.
• Avoid overcooking and browning food.
• Maximize deep sleep (during which the brain clears out debris).

5. Inflammation

Inflammation is a complex and multifaceted category of interactions between the immune system, cardiovascular system and molecular mediators. It is best to think of optimal inflammation as a balancing act — we want some, but not too much, well timed acute inflammation, and to avoid excess chronic inflammation. Day to day, we want to boost the readiness of the immune system without directly activating it, increase response to infectious agents while reducing chronically elevated inflammatory cytokines, and minimize auto-immunity.

• Follow a regular program of exercise activity.
• Eat an unprocessed plant-based diet.
• Supplement deficiencies in the diet (verified by blood testing).
• Supplement with nutraceuticals that target inflammation in the ways described above.

6. Immunosenescence

Related to inflammation is the concept of aging of the components of the immune system. Immune stem cells provide parent cells for the whole system, and if they become damaged over time then they lose self-renewal capacity and the whole immune system loses functionality — for example Natural Killer Cells become less powerful against pathogens, and antibodies become less diverse and lose affinity.

7. Cellular and Mitochondrial DNA Repair

All of the above factors heavily tie into this concept: the programming code for upkeeping the body’s cells, and the cell’s power stations (mitochondria), becomes scrambled or deleted over time. If there’s no code, then the body cannot make proteins properly and we see increases in risk of disease.

We need to protect our body’s “programming code” to live a long time, if it stays in tact, this involves reducing oxidation, glycation, inflammation, and damage from pathogens — but also repair mechanisms. The body can surgically fix code errors, and destroy cells with broken code, and there seems to be ways to boost this ability.

8. Major Health Markers

Cancer and Cardiovascular Disease are the top two age-related killers. Early detection and treatment are paramount to surviving as long as you can.

When it comes to cancer, doctors can measure many markers for tumors. The list is long, for more details you can read here.

Cardiovascular disease can be monitored via readings of blood pressure, blood lipids (LDL, HDL, triglycerides, count, size and oxidation) and blood flow.

9. Nutraceuticals

In the table below, we’ve put our favourite longevity-promoting nutriceuticals. Realistically, not everyone will benefit from taking any/all of them, but if you’re taking a very proactive approach, or feel you need support in any of the categories, then do some further reading on each of these compounds…

As you can see, with these 5 compounds, we cover all of the bases quite well!

Berberine is a particularly interesting one because it also activates AMPK, which is known to control the aging process impactfully. In this regard it is comparable to the Metformin, which is touted as one of the top three most promising anti-aging pharmaceuticals. Berberine does everything Metformin does plus more.

While there is insufficient evidence for Ashwagandha, Rhodiola and Reishi having impacts on lifespan, they probably impact healthspan, and we think they have great potential as anti-aging nutraceuticals. We encourage more research on these compounds in the hopes of seeing some interesting findings. Other promising supplements are Alpha Lipoic Acid, Baby Aspirin, also the amino acids ALCAR, Beta-Alanine, Taurine, Glycine, and energy system components like H2 hydrogen and NAD+.

10. Unique Pharmaceuticals

Two really promising pharmaceuticals are:

• Rapamycin: It inhibits mTOR, which is a powerful cell growth, proliferation, motility, survival, protein synthesis, autophagy, and transcription regulator.
• Selegiline: Is a MAO-B inhibitor and neuroprotectant, it reduces the creation of damaging radicals in the brain, which slows brain aging

Both of these compounds have been studied extensively in animals — mice, rates, dogs, monkeys. They each work through independent pathways to extend life, so are more likely to be synergistic than other pairings, but this needs to be tested so we encourage research in this area. They each require very low doses (~1 mg/day). One should work with a doctor to monitor side effects of using these drugs. Piracetam doesn’t make the list because lack of evidence, but we think it has potential too.

11. Blood Tests and Health Markers

If you are wealthy or have health insurance, you should check over your body’s metrics with a doctor. If you come across any problem areas, discuss with your doctor and dieticien how you might fix those problem areas. Here is a list of things you might want to measure, it might take a few visits to get them all done, if time or resources are a limitation then start from the top and work your way down:
- vitamins and minerals
- fasting glucose
- blood count w/ differential
- hbA1c and Hcy
- liver and kidney markers
- testosterone, estrogen, including ‘free’
- cortisol and thyroid panel
- fodmaps allergy testing
- inflammation (e..g ESR, CRP and PV)
- heavy metals (e.g. lead, mercury, arsenic)
- pregnenolone and dhea
- progesterone and dht
- ghrelin and leptin
- o3 fatty acids and igf1
- fibrinogen

12. Hormone Replacement Therapy

We think that as we age it is important to maintain youthful levels of most hormones. Hormone replacement therapy, like all other therapies, should be personalized. It is important to work with a longevity-friendly endocrinologist when establishing what are the correct dosages for you. Discuss with them this list of hormones, and after getting blood tests, see which are relevant to you. If you get tested and have high-normal levels of a certain hormone then there’s no reason to replace your natural levels.

This is perhaps an overly-comprehensive list of things to ‘replace’, but if one is not constrained by money, and one is old enough to benefit, then we think they would likely optimize healthspan and lifespan. When considering hormone replacement therapy, ALL hormones should be considered important, they each play a role in energy, sleep regulation, immune function, neuroprotection, mood and addiction reinforcement, etc…

• Boron: While not a hormone, it’s important for making hormones freely available to the hormone receptors by reducing Sex-Hormone Binding Globulin. [5–10 mg/day].

The following can be used by both sexes. The average blood concentrations for all of these will likely reduce over a lifetime.

• Melatonin: is important not just important for the aging factors described above, but also for the circadian rhythm and sleep quality. [0.3–3 mg/day].
• Pregnenolone: is important for mitochondrial health and is the precursor for all other hormones. It modulates dopamine and endocannabinoid signalling and so contributes to mood and cognition too. [5–50 mg/day].
• DHEA: counterbalances cortisol and acts as a neuroprotective, mood enhancing neurosteroid. [5–50 mg/day].
• Ghrelin: Ghrelin is important for deep sleep, tissue repair, and may protect against cognitive decline. Ibutamoren is a Ghrelin receptor agonist and a growth hormone secretagogue. While growth hormone signalling is associated with higher mortality by itself, this effect is likely rescued by ghrelin signalling via sirt1. [5–25 mg/day].

These next hormones have sex-specific dosage ranges.

• Testosterone: Testosterone is important for sex drive, mental vitality and muscle mass. Having muscle mass is important for life quality and reducing the risk of falls. Dosing too high may increase risk of atherosclerosis, balding and prostate cancer. Testosterone is important for women too, and they should not be afraid of taking it as part of their hormone replacement therapy, but should be careful to avoid doses that cause virilization.
  - MEN: [75–250 mg/week].
  - WOMEN: [2–15 mg/week].
• Progesterone: Progesterone is important for sleep, cognition and mood, sex drive and appetite, metabolic rate, bone and joint health. Dosing too high may lead to daytime sleepiness and fat gain. It is important to use a bioidentical progesterone like Prometrium, as synthetic forms like medroxyprogesterone have been associated with problematic outcomes. It competes for an enzyme that converts testosterone to it’s balding metabolite, and regulates estrogen receptor integrity. It is often thought of as a female hormone, but is important for males too.
  - MEN: [5–200 mg/night].
  - WOMEN: [50–400 mg/night].
• Estrogen: Estradiol is important for reducing risk of cardiovascular disease and cancer, improves mood and sleep, and bone and joint health. It is important to use bioidentical estradiol, as synthetic forms such as ethinylestradiol and tibolone have been associated with problematic outcomes. Estrogen is important for men too, but men taking testosterone likely won’t need extra estradiol due to aromatization. Some males may require aromatase inhibitors if their body aromatizes too much testosterone in their old age.
  - POSTMENOPAUSAL WOMEN: [0.025 to 0.1 mg/day] transdermal patch.

13. Cryonics

Cryonics may seem like a silly science fiction, but it is an actual technology that exists today. If you plan on living a long time, you’ll need to take advantage of future medical technology. If you die before an effective treatment is invented, getting cryonically vitrified will give you a non-zero chance of being revived and treated in the future. If you do not get cryonically vitrified then your chances of survival after clinical death are zero.

Look around for a local cryonics company and sign up as soon as it’s financially viable. You can discuss with the company, and your insurance, to see if you can have your life insurance go towards your cryonics treatment.

14. Gene testing

Once you’ve checked on all your vitals and set up a plan for cryonics, the next stage will be getting your genes tested. Find a trusted gene-testing service and look for problem-mutations. It is recommended spend some time anonymitizing your data — don’t use your real name and details when registering the DNA samples, so as to avoid hurdles in the future (insurance companies will want to make adjustments to your premiums, and malicious groups may try to do something nasty with the data). Run your data through an interpretation-analysis service, and once you know of problematic mutations you can work with a health specialist.

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Be happy and stay healthy peeps 😀

— The Hapi team.