Dear Future Centenarian,
The four weekly newsletters you got starting the third week in November described in detail how to best help you convince those you love most (and anyone else) to improve their lifestyle habits to avoid disease and suffering… and to add youthful years.
In a nutshell, it was the art of friendly persuasion.
I even included some resources for them to make the transition easier and most effective.
Those resources included little known recent inexpensive breakthroughs that actually REVERSE important aspects of aging. Imagine becoming biologically younger in 2021 than you were last year!
I thought I said all I was going to say about that until a couple of days ago when two emails landed in my inbox from two genius friends.
The following are their newsletters. The first is from a friend of nearly 20 years, John Carlton.
John is one of the more brilliant and successful advertising minds on the planet. In order to ascend to that rarified air, one must become a skilled philosopher, psychologist, historian, salesman, writer… and a student of life. More than anyone I know, John figured out what makes people tick.
Now he teaches his skills to others. https://www.john-carlton.com/
Here’s his letter:
Have you ever stopped to think just how freaking stubborn people can be?
I mean, how insanely stubborn, to the point of self-sabotage?
I used to ask students to partake in an experiment: Try getting one of your pals to go see a movie.
Make sure it’s a movie they would like. And probably go see on their own.
Tell them how much you loved it, and that they just GOTTA go see it themselves.
… see what happens next.
It’s astonishing how often your BFF, upon being told how awesome a movie is, how much they’d like it, and especially how much YOU liked it…
… will thereafter refuse to go see it themselves.
Go try it.
The stories any salesman can tell you about the roiling stubbornness of prospects are legion.
Even when their own self-interest is at stake.
They just won’t. Won’t buy, won’t click, won’t pick up the phone, won’t walk four steps to pick up a free sample.
This is a core lesson for anyone trying to sell something to someone else (and yes, you’re “selling” that movie to your buddy).
People will outright refuse to do things that will make their lives better.
Without a good reason. Without any logical explanation. Without even knowing themselves why they’re being so stubborn.
This is what you’re up against, when you’re in biz.
And understanding that good salesmanship entails much more than simply telling someone to do something will ultimately change your life.
You gotta master the sneaky skills of real persuasion.
Does that strike a chord? If you ever tried convincing anyone to do anyone to do something good for themselves such as improving their health and longevity, you probably know what I mean.
The second letter is from Joe Polish, an extremely close friend for over 25 years. People pay him $100,000 per year to spend three weekends a year with Joe along with others who invest the same in order to exchange ideas and business, health and success strategies… and they do it year after year.
Joe reminds us that life “Gives to the giver and takes from the taker.
I have never met a more generous person, and his integrity is beyond reproach. Learn more about Joe at https://joepolish.com/.
Here’s his current letter. Note the similar topic as John’s:
When you want to connect with anyone, ask this simple question first: “How can I help?”
Connecting requires a couple things, such as: asking, courage, and not coming across as an opportunist who only cares about themselves.
People sometimes have trouble connecting because they are SO focused on what THEY want.
It never occurs to them to ask: “What does the OTHER PERSON want?”
Instead, ask: What’s in it for THEM?
Why should the person you’re trying to connect with care about you UNLESS you show up with a reason that should make them care?
Your Opportunities are important to you.
The way you see the world is important to you.
But that doesn’t mean anyone should care about what is important to you.
No matter who someone is, there is likely an area of their Life where they are completely broken and lost.
The façade of someone being “important” or “special” goes away when you’re sitting with a billionaire, or a famous athlete, musician, or politician that has an area of their life where they are not only messed up, but doing things that would publicly be perceived of as “bad”… AND they are hurting themselves (and sometimes other people).
This is the type of experience that gives you a whole other perspective on humanity.
What helps you to connect is the ability to identify suffering in other people, and to ask yourself: “How can I help reduce or remove that suffering?”
So there you see it. John points out that by asking someone to do something specific, even if it’s something they might do if you kept your trap shut, they tend to throw up a wall of resistance.
Joe says not to assume you know what’s good for them. Engage in conversation and slowly draw out their biggest personal concern… the thing or things that are giving them pain.
It may not even be a health issue, and it might take several artful conversations to find out what that might be. If it’s not health-related and you can help them with it, you could help them twice. They’ll feel more comfortable in opening up about their health, their fears of mortality and knowledge of and opinions on extreme longevity.
If it happens to be a health issue, you have established rapport.
Now you’re in position to help them without automatic resistance.
Remember – Someone in good health has a thousand problems. One in bad health has only one.
An Update on Progress at Tissue Engineering Company Lygenesis
The development programs conducted at Lygenesis came about as a result of an academic researcher who followed up on the realization that the positioning of some organs in the body is arbitrary.
Much of the function of organs like the liver and the thymus could be carried out in any location that is well-supplied with blood and easily accessible to roving cells. The liver is a chemical factory, producing and consuming various proteins and metabolites.
The thymus is a cell factory; thymocytes migrate to the organ from the bone marrow, and once there are transformed into T cells of the adaptive immune system via their interaction with thymic tissue.
Tissue engineering of functional liver or thymus tissue from the starting point of a patient cell sample is a going concern, but the inability to produce dense networks of capillaries limits this to the production of very small organoids, a millimeter or two in cross-section at most.
Any larger than that and nutrients cannot reach the innermost cells, which will die. An organoid grown from matched cells can be implanted into the body, where under optimal circumstances it will become connected to the vasculature.
Exercise as a Mild Senotherapeutic
Exercise is known to improve health and extend the healthy portion of life span, but not extend life span itself in mice.
This is a much lesser effect than that of calorie restriction, which does extend maximum life span in addition to improving health. From a very high level view, both exercise and calorie restriction are similar, in that they trigger many of the same stress response mechanisms, making those mechanisms work harder to maintain cell function than they would otherwise have done.
A Sensible Consideration of the State of the Art in the Treatment of Aging as a Medical Condition
It used to be the case that one could write up a summary of where the research community stood on the treatment of aging as a medical condition (which was varying shades of “not that far along towards practical applications, but definitely promising if they get their act together”) and then not have to update it all that much for years.
Research is slow and uncertain, for one, and secondly there was, for decades, a strong cultural prejudice in the scientific community against trying to apply what was learned about aging to the treatment of aging. Little progress was made as a result.
Matters are proceeding much more rapidly nowadays.
An Example of High Dose Fisetin Exhibiting Senolytic Effects in Mice
Fisetin is perhaps the most intriguing of the first generation senolytic compounds, those capable of selectively destroying senescent cells in old tissues and thus producing rejuvenation to a meaningful degree.
Senolytics have been demonstrated in animal studies to reverse many age-related conditions to a greater degree than any other approaches. Why is fisetin intriguing? Because in mice, it appears to be about as effective as the dasatinib and quercetin combination, yet it is a widely used dietary supplement.
Supplement dosing of fisetin in humans is not that much lower than the lowest demonstrated senolytic dose in mice.
Arterial Stiffening with Age Correlates with Structural Damage to the Brain
Today’s open access research paper is a reminder of one of the more direct mechanistic links between vascular aging and brain aging.
Blood vessels stiffen with age, becoming progressively worse at the necessary task of contracting and relaxing in response to circumstances. This is in part due to cross-linking in the extracellular matrix, in which advanced glycation end-products (AGEs) such as glucosepane form persistent bonds that collectively alter tissue properties.
Moonshots for the Treatment of Aging: Less Incrementalism, More Ambition
There is far too much incrementalism in the present research and development of therapies to treat aging. Much of the field is engaged in mimicking calorie restriction or repurposing existing drugs that were found to increase mouse life span by a few percentage points.
This will not meaningfully change the shape of human life, but nonetheless costs just as much as efforts to achieve far more. If billions in funding and the efforts of thousands of researchers are to be devoted to initiatives to treat aging, then why not pursue the ambitious goal of rejuvenation and adding decades to healthy life spans? It is just as plausible.
Frail Older Individuals Exhibit a Worse Response to Vaccination
Frailty is usually accompanied by greater immune dysfunction, given that chronic inflammation is a strong component of both immune aging and the various dysfunctions of frailty.
A Subset of Fat Tissue Cells is Largely Responsible for the Inflammation Generated by Excess Visceral Fat Tissue
Scientists here suggest that the chronic inflammation generated by visceral fat tissue, an important form of metabolic disarray that drives age-related disease and dysfunction, is not produced by all fat cells.
Indeed, it may be primarily produced by a specific type of progenitor cell lining blood vessels in fat tissue. This is an interesting demonstration, but it remains the case that the best solution to excess visceral fat is never to obtain it in the first place. The effects of visceral fat on metabolism quite literally accelerate the progression of degenerative aging.
Declining Resilience as a Manifestation of Aging
Resilience, meaning the ability to recover from wounds, infection, and other forms of damage, is more or less the flip side of frailty in aging. Frailty increases, resilience decreases.
Historical Gains in Life Expectancy Occurred at All Ages, not Just Due to Reduced Child Mortality
Historical gains in life expectancy in the past two centuries, much of it occurring prior to the advent of effective antibiotics, were largely a matter of control over infectious disease via public health measures such as sanitation, coupled to a rising standard of living.
A sizable amount of the gain in life expectancy at birth is due to reduced infant mortality, but this isn’t the whole story. It is worth noting, as in this article from a few months ago, that the data shows remaining life expectancy at all ages heading upward over time. Reducing the burden of infectious disease has effects at all ages, not only due to incidence at a given age, but also by reducing the accumulated damage due to serious infections suffered throughout life.
A Report from the 7th Annual Aging Research and Drug Discovery (ARDD) Meeting
Most 2020 conferences were held online as a result of COVID-19, curtailing the networking, discovery, and serendipitous discussion that is most of the point of attending a conference. Presentations were still given and research results announced, however. It remains useful to glance over conference reports for a sense of the mood and focus of the academic research and clinical development communities.
Ageless: The New Science of Getting Older Without Getting Old
Ageless: The New Science of Getting Older Without Getting Old is a forthcoming book discussing the aging research community and its newfound interest in treating aging as a medical condition.
Nanomaterials for the Clearance of Senescent Cells
Senescent cell accumulation is a contributing cause of aging, and targeted destruction of senescent cells with senolytic therapies produces a meaningful degree of rejuvenation and reversal of age-related disease in animal models.
First generation senolytics are largely repurposed small molecules. Second generation senolytics will include a range of more carefully designed strategies, including the nanoparticles allowing for selective delivery of therapeutics to senescent cells that are the topic of this open access paper.
Such nanoparticles can be used as the basis for both detection of senescent cells and their destruction, a promising attribute in the present environment in which there is as yet no widely available and reliable method of assessing the burden of senescence in human patients in a cost-effective and minimally invasive way.
Targeted Delivery of a Short-Lived Radioactive Compound to Cancer Cells
The power of specific targeting of specific cell types is that any cell-killing mechanism can then be delivered. The more efficient the targeting, more dangerous and effective the cell-killing mechanism can be.
The reason why any given cancer therapy is less effective at killing cancer cells than it might be is because the targeting isn’t perfect, and thus there is the need to limit the damage to other tissues in the body.
Event Report: Aging, Geroscience and Longevity Symposium
Most the events of the past year relating to longevity science were held virtually, thanks to the ongoing pandemic and the reaction to it. Here find notes and presentation video from the Aging, Geroscience and Longevity Symposium that was held last year, discussing an eclectic selection of research into aging and the treatment of aging.