Methylation pattern differences are being used rather than mortality on health outcomes as mortality takes longer to reveal and makes anti-aging trials prohibitively expensive. Methylation clocks as endpoints is a new idea, if it works it will be 100 times cheaper and 10 times faster. In a revolutionary step there will be enough bandwidth to test a dozen different measures at once.
Many known measures are thought to increase life expectancy, researchers want to know which ones offer greatest benefits, now they interact, synergize, and interfere with one another. Combining berberine with gynostemma and metformin may offer additional life expectancy compared to any one separately; panoply of different anti-inflammatory strategies may be improvement over an aspirin a day. This is being taken on with hopes of exceptions such as if 2 different measures act via different metabolic pathways there is reason to hope effects compound; such as life extension interventions based on mitochondrial health synergize with interventions based on rebooting the immune system which may extend life with these 2 measures together greater than separately.
By study design participants will not be told what to eat or exercise, rather ask what they are doing, eating, and supplements via detailed questionnaire. Subjects will be selected to represent a broad array of different strategies and combinations. There will be enough statistical power to estimate interactions among every pair of measures out of 12 as independent variable are taken, which will be chosen in advance to have clear focus.
Criteria proposed will be that each measure separately should have human longevity or mortality data backing it up; measures should be easily available to all; measure should be well enough known to be common use; non-smoking; none to little alcohol consumption; at least 5,000 IU vitamin D daily; multi-mineral supplement with chromium, selenium, magnesium, and zinc; exercise equivalent to 5 hours minimum a week.
BMI is an important part of life and longevity factor that is difficult to account with most studies showing a BMI between 21-25 is associated with a maximum lifespan an some saying lower is beneficial. Apparent paradox is due to some individuals having genetic disposition to being overweight or underweight; genetically underweight tend to overeat without social stigma and those genetically overweight feel compelled to diet.
There are a list of things being considered that may help lengthen life such as: love men in relationships have 7% lower mortality, women 4%, while loneliness increases mortality by 50%. Staying employed can add up to 14 years of empowered extended life. Anti-inflammatories attribute to life expectancy. High fiber and healthy gut flora and vegetable based diets can help with maximal life expectancy. Meditation has encouraging data to telomerase activity. Intermittent fasting extends life and lowers mortality in nursing home studies. NAC, DHEA, Metformin, Rapamycin, Quercetin, Dasatinib, Epithalamin, Selegiline, and Deprenyl have all been used in studies to increase lifespan. Interval training is reputed to be most efficient path towards cardiovascular health.
These things would be put into combinations likely to be redundant to cluster different strategies together and condense more into a manageable list to be analyzed such as:
- Anti-inflammatories (aspirin, ibuprofen, statins, omega 3, curcumin, boswellia)
- Blood sugar control (metformin, berberine, gynostemma, chromium)
- Social factors (family, employment, wealth, community support, marriage, sex, communing with nature, empowerment)
- Mitochondrial supplements (NAC, CoQ10, PQQ, NR, melatonin, glutathione, carnosine, ALA)
- Immune support (reishi mushrooms, cistanche, andrographis, goldenseal, echinacea)
- Adaptogens (rhodiola, ashwagandha, bacopa, silymarin, pycnogenol)
- Telomerase activators (silymarin, astragalus, ashwagandha, horny goat weed)
- Senolytics (quercetin, dasatinib, fasting)
- Diet (everything from high-protein to high fiber to vegan to paleo in one cluster?)
- Limiting and intermittency of diet (long- and short-term fasting, CR, BMI)
- Exercise (aerobic, strength, interval, walking, competitive sports, yoga)
- Mental focus (meditation, prayer, yoga, tai chi, spiritual practice, caffeine)
- Neuroprotective (ashwagandha, rhodiola, ginkgo, melatonin, bacopa, selegiline, gotu kola, coffee, tea, blueberries, chocolate)
- Multivitamin supplements (including mega D, mega-C, B12, carotenoids and tocopherols)
- Sex and steroid hormones (DHEA, prostaglandin, progesterone, SAMe, testosterone)
- Angiotensin inhibitors (Lotensin, captopril, enelapril)
The first thing to be done will be to identify outliners who stand out from the rest to determine what they have in common. This approach gives flexibility to show what is wanting to be known with disadvantage to imagine patterns in a small set of random error possibility. If there are no or only a few individuals among 5,000 aging more slowly without common thread to be found data on anomalies or mistakes must be explained. If dozens are found with overlapping strategies then there is a solid foundation for personal life extension habits, and a clear hypothesis for further experiments has been provided.
