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☴ Xun SE

• Element: Yin Wood (Yi)
• Number: 4
• Individuals: Eldest daughter, widow, monk, sister-in-law
• Body: Arms, thighs. Diseases related to "wind" and gas accumulation. Gall bladder, arteries, veins, limbs
• Commerce: Successful commerce with wood, plants, fruits

☲ Li S

• Element: Fire (Yin and Yang)
• Number: 9
• Individuals: Middle daughter, writers, people with a bulky abdomen, soldiers, people with congenital eye problems
• Body: Eyes, heart, San Jiao (the three focal points), small intestine
• Commerce: Commerce with newspapers, magazines, and books, can be very successful

☷ Kun SW

• Element: Yin Earth
• Number: 2
• Individuals: Mother, stepmother, farmer, villager, corpulent people
• Body: Abdomen, spleen, stomach, skin, tissues, muscles, tumours
• Commerce: Real estate business

☳ Zhen E

• Element: Yang Wood
• Number: 3
• Individuals: Eldest son
• Body: Legs (especially from the knees down), hair, voice, liver, gall bladder, arteries, veins, limbs
• Commerce: Trade in tea, wood, plants (medicinal)

☱ Dui W

• Element: Yin Metal (Xin)
• Number: 7
• Individuals: The young girl, mistresses, singers, actors, translators, sorcerers, slaves
• Body: Tongue, mouth, throat, lungs, phlegm, saliva, large intestine, brain
• Commerce: Not a favorable trigram for commerce

☶ Gen NE

• Element: Yang Earth
• Number: 8
• Individuals: Youngest son, teenagers, those with plenty of free time, hermits
• Body: Fingers, bones, nose, back, sacral area ("coccyx"), skin, tissues, muscles, tumors

• Element: Water (Yin and Yang)
• Number: 1
• Individuals: Middle son, fishermen, pirates, sailors
• Body: Ears, blood, kidneys, bladder

• Element: Yang Metal
• Number: 6
• Individuals: Father, emperor, famous people, bosses, leaders
• Body: Head, bones, lungs, large intestine, brain
• Commerce: Trade in gold, gemstones, jewlery, luxury items

What is Ejection Fraction?

Types of Normal Ejection Fraction

There are two main types of normal ejection fraction

Diagnosing and Treating Heart Failure

Expertise in Heart Health

Importance of a Healthy Heart

Conclusion

• A decline in the number or health of stem cells available – which could be addressed by the introduction of new stem cells
• An accumulation of cells that are in a senescent state – which could be addressed by bolstering the innate biological mechanisms that normally break down these senescent cells
• Damage to the long-lived proteins in the extra-cellular matrix that normally supports cells, with results such as the stiffening of arteries – which could be addressed by a variety of mechanisms including breaking crosslinks between adjacent proteins.

• Identify and research mechanisms that have the potential to remove or repair aspects of the damage
• Determine how these mechanisms might be applied in practice
• Consider and monitor for potential side-effects of these mechanisms, and, as required, design modifications or alternatives to them
• Consider and monitor for potential interactions between various such mechanisms.

• A wide set of potential damage repair interventions that deserve further study
• Early encouraging signs that damage repair can extend healthy lifespans in various species
• A general pattern that slow progress in a field can transition into a new phase with much faster progress
• Ways in which “breakthrough initiatives” can trigger such a phase transition for the project to achieve LEV.

1. Identifying and improving the repair mechanisms that already work within the human body when we are younger – before these mechanisms lose their effectiveness
2. Learning from the special self-repairing features of the small proportion of humans who are “superagers” in the sense that they reach the age of 95 without having suffered any of the usual age-related diseases such as heart disease, cancer, dementia, or stroke
3. Learning from the fascinating self-repairing features of numerous species which avoid various age-related diseases, and which can retain their vitality for decades longer than other species with whom they share many other characteristics
4. Learning from other regenerative features that various species possess, such as the regrowth of damaged limbs or organs, as well as the birth of a baby whose cells are aged zero from parents who can be many decades older
5. New interventions that don’t exist anywhere in nature, but which can be introduced as a result of scientific analysis and engineering innovation (relatively simple examples are blood transfusions, and stents that can repair a narrowed or blocked blood vessel; more complicated examples involve nanobots and 3D printing)

• The seven links included in the table on this page, “A Reimagined Research Strategy for Aging” at the SENS Research Foundation
• The trials listed in “The Rejuvenation Roadmap” maintained by Lifespan IO
• The comprehensive survey of interventions catalogued at the “RAID – Rodent Aging Interventions Database” maintained by the LEV Foundation
• The AgingDB database of pharmacological trials targeting aging
• A recent review in Nature, “The long and winding road of reprogramming-induced rejuvenation”
• The TRIIM trials to rejuvenate the human thymus.

• None of these treatments, so far, have resulted in animals passing the LEV threshold
• The extension of healthy lifespan achieved in these trials is generally less than 50%, and is usually significantly less than that
• Results obtained in experiments with shorter-lived animals, such as mice and rats, often do not translate into similar results with humans (or have not done so yet).

• The various trials indicate that at least some rejuvenation can be engineered, and that there are multiple ways of doing so
• Trials of combinations of different rejuvenation treatments (which might be expected to have more substantial results) are still at an early stage
• Nothing like a proof of impossibility has been found, or even seriously suggested
• The total amount of resources dedicated to this field is far below that in many other fields of scientific research; the field might, plausibly, be expected to make faster improvements if it gains more support.

The possibility of a phase change

• The availability of re-usable tools (such as improved microscopes, molecular assembly techniques, diagnostic tests, or reliable biomarkers of aging)
• The availability of important new sets of data (such as population-scale genomic analyses)
• The maturity of complementary technologies (such as a network of electrical recharging stations, to allow the wide adoption of electric vehicles; or a network of wireless towers, to allow the wide adoption of wireless phones)
• Vindication of particular theoretical ideas (such as the paramount importance of mechanisms of balance, in the earliest powered airplanes; or the germ theory for the transmission of infectious diseases)
• Results that demonstrate possibilities which previously seemed beyond feasibility (such as the first time someone ran a mile in under four minutes)
• Fear regarding a new competitive threat (such as the USSR launching Sputnik, which led to wide changes in the application of public funding in the United States)
• Fear regarding an impending disaster (such as the spread of Covid-19, which accelerated development of vaccines for coronaviruses)
• The availability of significant financial prizes (such as those provided by the XPrize)
• A change in the attitude of researchers about the attractiveness of working in the field
• A change in the public narrative regarding the importance of the field
• The different groups who are all trying to find solutions to problems in the field finding and committing to a productive new method of collaboration on what turns out to be core issues.

1. Lack of funding for some of the experiments that would produce important new data, since commercial interests such as VCs see little prospect of them earning a financial return from supplying that funding.
2. Some people who are in a position to supply funding to support important experiments choose not to do so, because they are dominated by a mindset (sometimes called “longevity myths” or the “pro-aging trance”) that it’s wrong to support significantly longer lifespans.
3. More broadly: society as a whole assigns insufficient priority to the comprehensive prevention and reversal of age-related diseases.
4. Some potential supporters are deterred by what they perceive as irresponsible or untrustworthy aspects of the longevity field (snake-oil solutions, uncritical claims, tedious infighting).
5. There is disagreement or confusion about which experiments are most important; as a result, available funds are being misdirected into, for example, less useful “lifestyle research”.
6. Related: there is no agreed list of which experiments (or other research) should be conducted next, once additional funds become available.
7. In the absence of biometrics that are accepted as being good measurements of overall biological aging (as opposed to measuring only an aspect of biological aging), it’s hard to know whether treatments increase the life expectancy of any long-lived animal.
8. It’s likely that pools of data already in existence contain important insights related to aging and its possible alleviation – namely biological and other health data about individuals as they age and pass through different experiences and treatments. However, much of this data is kept in proprietary or private databases and isn’t made available for scrutiny by other researchers. Especially with the greater power nowadays of data analysis tools such as deep learning, the potential for open analysis isn’t being achieved. (This is another example where commercial or personal concerns are preventing the development of public goods from which everyone would benefit.)

The breakthrough initiatives

• To clarify which experiments and research have the biggest potential for dramatic results
• To avoid behaviours or statements which alienate or deter important potential supporters
• To reduce amounts of wasteful duplication and “noise”
• To develop and publicise meaningful quantitative metrics of progress toward LEV
• To share more openly both the successes and the failures of experiments conducted, to allow more effective collaborative learning.

The breakthrough narratives

1. Building on top of the latest “longevity dividend” and “evergreen society” arguments in the new book by the economist Andrew Scott, The Longevity Imperative: How to Build a Healthier and More Productive Society to Support Our Longer Lives, to highlight the broader economic and social benefits of biorejuvenation treatments
2. The fascinating learning that can be obtained from looking more closely at the damage repair mechanisms already utilized by some “superaging” animal species; more and more of these mechanisms are being discovered and explored, and deserve greater publicity.
3. Additional learning that can be obtained from further study into human superagers. Note that, for evolutionary reasons, it is likely that different superaging families around the world employ different biological damage repair mechanisms.
4. The RMR narrative that the particularly useful data to collect is that from the combination of multiple treatments administered in mid-life; as this data accumulates, it is likely to give rise to lots of new theories about interactions between these treatments.
5. The attractiveness of extending the RMR projects (for the robust rejuvenation of middle-aged mice) to similar investigations that might be called RDR (focused on dogs) and RSR (focused on simians, that is, monkeys and apes).
6. The ups and downs of the various teams that are entering the XPrize Healthspan – a contest that can be seen as promoting an “RHR” extension (the ‘H’ for “human) to the RMR / RDR / RSR progression mentioned above
7. A new analysis to supersede the existing “hallmarks of aging” diagrams, with a richer model of the interactions between different types of aging damage and the different possible damage repair mechanisms.
8. Exploration of some “left field” rejuvenation interventions, such as those of Jean Hébert about growing and using replacement organs (including gradual replacement of parts of our brains), and those of Michael Levin about the ways in which the electrome can trigger biorejuvenation.
9. The new possibilities that are continuing to emerge that take advantage of CRISPR-style genetic reprogramming and the reprogramming of epigenetics by Yamanaka factors or other means.
10. More powerful AI platforms can enable faster advances in fields of science than were previously expected; examples include AlphaFold by DeepMind and the so-called menagerie of AI models utilised by Insilico Medicine
11. Further championing of the ideas of anti-death philosopher Ingemar Patrick Linden from his book The Case Against Death.
12. Engaging new video versions of some of the above narratives, in the manner of the CGP Grey video of Nick Bostrom’s allegory “Fable of the Dragon Tyrant” and those in the “Aging” YouTube playlist of Andrew Steele.

A probability, not a certainty

• Distractions and loss of focus
• Too much infighting and lack of constructive collaboration
• A decline in the understanding and use of scientific methods
• The field becomes dominated by pseudoscience, uncritical hero-worship, snake-oil, or wishful thinking
• A growth of societal irrationality and preference for conspiracy thinking
• An adverse change in the global political and geopolitical environment
• The triggering of one or more of what I have called “Landmines”.