By Vince Giuliano with comments by James P Watson
We have come to the end of a year and a start of another, and this has led me to musing about what I have learned in 2013. I have been studying the health and longevity sciences for nearly eight years now, so it is interesting for me to ask myself how my views have changed in the course of just the last year. Here, I share 13 items that are particularly vivid for me – a personal list of headlines for health and longevity in 2013. The stories following each of these headlines are either already told in other blog entries or will be told soon. I conclude with four additional items related how to my own personal professional situation is evolving.
Jim Watson comments briefly on a few of these items here. Jim has also drafted a separate blog entry on how his views have evolved in the course of the last year. I expect that we will publish that very soon.
My list is highly personal:
- Major determinants and symptoms of human aging appear to be stoppable and even reversible. This was a strong hunch going into the year. However, research findings published during the year lead me to be considerably more confident that this is so. Jim lists some of these findings below.
- As these proximate determinants of aging become clearer, three key central interventions for drastically slowing aging appear to be a. upregulating expression of the SIRT1 protein expression (via Resveratrol, etc), b. upregulating nuclear expression of NAD+ (via NMN or certain dietary supplements), and c. taking a supplement that acts as a powerful mitochondrial antioxidant (quite possibly, C60-olive oil or MitoQ).
- Jim Watson and I believe we are sneaking up on creating an overall GUT (Grand Unified Theory) of aging and biology, health and aging.. See the recent blog entry of the topic.
- I believe we have already passed Kurtzweil’s “singularity point” (ref) where humans together with computers transcend the limits of our strictly biological systems The rate of accumulation of important biological knowledge already exceeds anyone’s ability to fathom what it all means when it is put together. Internet information storage and searching, electronic communications, databases, sequencing and computer systems modeling are part and parcel of our existing discovery and knowledge integration processes. We could never have gotten this far without them. The true record of our progress is not in anybody’s mind or in any book or sets of books. It is out “in the cloud.”
- The application of life-extending interventions via two or more independent pathways can result in life extension that is greater than that expected by adding the results of the two pathways. As organisms, we are an extremely complex systems consisting of multiple positive and negative feedback circuits. Linear responses are by far more the exception than the rule. A way to evaluate the effectiveness of a set of longevity interventions is to ask whether the resulting benefits of applying them together exceeds what the benefits would be if the results were additive.
- Three key questions remain foremost when assessing biological impacts of substances and health interventions. These are a. dosage. Is it hormetic,sub-hormetic, or supra-hormetic, b. age and disease state of the organism. Interventions that can help sick or elderly people may show no effects in young healthy people, and c. time of day, since the expression of hundreds of response genes are controlled by circadian rhthyms. Clinical trials that do not take these factors into account may be meaningless.
- Many more biological processes take place through interactions and communications among multiple species than I had hitherto appreciated. The theoretical and practical implications of this for our health and longevity are vast.. The gut biome (actually different biomes in different segments of our intestinal track) is being studied intensely but multiple other biomes are also in constant interaction with us (skin biome, mouth biome, vaginal biome, etc). And in biology in general, interdependency of species is more the rule than the exception.
- No single longevity intervention can be expected to have a profound effect. It is probable that any highly effective longevity program requires applying multiple disciplines and interventions including ones of exercise, other induced stresses, diet, taking of selected supplements, rest and sleep, dealing with mental challenges, and social/interpersonal interactions. Forms of dietary restriction may be key. You can’t keep your automobile young and functional by any single mechanical intervention. It is ridiculous to expect that a single intervention would work with something as complicated as the human body.
- Management of multiple stresses to make sure they are actually being experienced and in the hormetic range is an important aspect of any personal longevity program. Exercise remains a key stressor, but there are many other stressors as well that can be used for health maintenance. These include selective applications of heat, cold, hypoxia, and multiple types of molecules.
- Delivery of drugs and health producing phytosubstances encapsulated in nano-sized particles can greatly enhance their biological effectiveness and minimize side effects. Liposomal delivery is likely to be of increasing importance. The pharmaceutical industry recognizes this and is pursuing much research in nanoparticle-encapsulated delivery of drugs. I believe the same is true for health producing dietary phytosubstances.
- Biological processes both within and among individual organisms and among them are all about signaling communications. In this regard I have come to appreciate a. the key roles in evolution and in organisms today of the “Great God Gasses” like nitric oxide, carbon monoxide, ozone and hydrogen sulfide, and b. the key roles of biological nano-sized delivery packages like exosomes and micelles. We can expect to publish a great deal more in this blog about these substances and their roles and communication.
- We are only now beginning to unravel how the benefits of eating fruits and vegetables are conveyed. There is evidence that, in addition to providing health inducing phytochemicals, cells in fresh fruits and vegetables are still alive and deliver exosome-containing plant-based RNAs. These RNAs act in the same ways our own human RNAs do to control gene expression and produce xenohormetic health and longevity benefits in us humans.
- I believe we are approaching a point where most diseases can be prevented or, if caught early enough, their consequences reduced to nuisance status. That is, when faced with the initial signs or threats of any personal disease situation, it is becoming more and more often possible to figure it out well enough to reduce the disease to where it is gone or just a minor nuisance. This point is not yet reached, but I sense that it is coming. Up to now at least, this has been true for me. This is a dream for the future of medicine.
In short, I think we are getting somewhere and that the rate of that getting is significantly increasing.
Some personal shifts in 2013
Speaking about my personal situation, I have a few additional to add:
A. In the course of 2013 I have developed incredible collegial relationships which are furthering the research and publishing capabilities of this blog.
– The first such relationship is with James P Watson, as is clear from the blogs he has written and those we have written together. Jim is multi-dimensionally extraordinary. He is both a practical healer and practicing surgeon and a deep scholar, thinker and communicator when it comes to essentially all the frontiers of the health and longevity sciences. We are constantly communicating via e-mails and often frequent phone conversations as undertakings of sharing and mutual discovery. We have had three such conversations already today. Jim’s understanding of molecular biology and organic chemistry by far outstrips mine, and besides that he seems to have knowledge of contemporary medical practices that exceeds that of most other MDs I have encountered. He has insatiable curiosity, and it seems there is no arcane biological science or medical topic Jim can’t master in a few days. He is the person who has brought many of the items in this list first to my attention. Further, Jim is a passionate and compassionate person . He does not hesitate to bring his superb research knowledge to bear to assist friends with their personal health/medical issues. I am grateful for my relationship with Jim and humbled by it.
– Two other relatively new professional relationships are also of great collegial value to me. The first is with Melody Winnig, my wife of many years. Melody is the research surveillance person in my network, daily surveying the news and bringing relevant new research items to my attention and the attention of key other colleagues. I found six new e-mails this morning pointing to such items, and this is typical. My observation relating to the knowledge singularity point is because of the vast number of new and exciting findings that Melody in particular has been surfacing. Also, Melody’s knowledge of the health/longevity sciences, going back to 2011, is rapidly increasing. She is particularly interested in phytosubstances and their potential, has joined with me in creating our blog entries on the live food stress hypothesis, and she seems to be playing ever more active roles in my professional life. A second such relationship is with my son Michael Winnig Giuliano who has been very helpful to me in managing multiple priorities.
– Finally I need to acknowledge the collegial contributions of the readers of this blog and the emergence of probably powerful new and additional collegial relationships that are developing. In particular I mention Dr. Ed Dratz, Dr. Frank Williams, Chen Hue, and Dan Campagnoli and Victor who writes for this blog, and the increasing group of people who post highly intelligent and relevant comments on the blog and who e-mail me directly. You know who you are.
B. I have been home-experimenting with making and personally testing liposomal preparations of combinations of anti-inflammatory herbal extracts and dietary chemicals intended to enhance weight and metabolic processes. Liposomes are nano-sized particles with lipid outer layers that encapsulate the substances intended to be delivered into body cells There is much research going on in the pharmaceutical industry focused on liposomal drug delivery. These preparations are intended to enhance the bioavailability of the encapsulated substances by a large factor (6 or over) without incurring side effects. We believe the benefits of liposomal delivery can be realized for dietary phytosubstances such as resveratrol or EGCG as well as for drugs. This work has been with my son, Michael. We are in the very-early stages of this initiative and we have much experimental and laboratory analytical work yet to do. I expect to report on this work in this blog in due time.
C Having turned 84, I continue to be “healthy as a horse.” That is problem-free, healthy, strong and capable for the present. But like any horse or other living biological, I recognize that I am facing an inherently uncertain future. My intention and plan is to keep going in this game of life and at the game of science, learning, developing understanding and communicating. And I intend to do that for a very long time more. I want to be around for the process of truly fathoming aging and to contribute to that process until it is mostly complete. For now, this blog will continue to be a major vehicle for doing that.
A few Jim Watson reactions to my list
I sent a preliminary version of this list with Jim Watson, and the following comments are drawn from an email response. I have italicized the points Jim is responding to
1. Major determinants of aging may be stoppable and possibly reversible. Yes, I fully agree with
you! The most exciting things here that show potential in my opinion is the following:
a. GDF-11 for the heart and skeletal muscle, based on heterochronic parabiosis
b. CCL-11 antagonists for brain aging, based on HCPB experiments
c. NAD for activating all 7 Sirtuins and reversing Warburg-type metabolism.
d. IRS1/2 inhibitors for blocking the insulin/IGF-1 pathway
e. Mitochondrial-specific renewable antioxidants that also activate autophagy (I.e. Buttered Bucky balls)
f. Oral absorption of exosomes containing plant RNA or synthetic RNA that counteract many of the noncoding RNA that “screw-up” the Normal Post transcriptional regulation (Ex: circular RNA, linear noncoding RNA, etc)
2. Kurzweill’s singularity point – yes,I think we are getting near, yet when I see how “inept” humans are at taking knowledge and applying it to their own lives, I do not think that 99% of the mass of humanity will benefit. For instance, I have a dear friend who has had access to much cutting-edge knowledge about aging, yet never took it to heart (his lifestyle was atrocious! No exercise, overweight, ice cream diet, lack of sleep, and poor attitudes about life, no laughter, no spirituality, 3 wives, etc.) The problem of disconnect between knowledge and personal behavior will not be solved via any “Singularity”
3, Grand Unified Theory – This is what I am the most excited about! I am beginning to finally get a handle on the gases. I still do not understand the redox system, however. The two are clearly linked. I have been having an intense conversation with Dr. John Sturges about the clinical use of these gases and combining them with heat. Although the obvious gases are CO, NO, and H2S, we are spending just as much time researching ozone.
3. Being able to do something about individuals with diseases – As an example, I really think that we may be able to help a person I know with mild autoimmune disease – a combination of Lupus and Scleroderma with Raynaud’s syndrome, and with a MRSA susceptibility. We would use something called “ozone steam sauna” therapy. We think that the heat can break the cold-induced Raynaud’s vasospasms and also induce HO-1 (I found out that 20 min of 42 C will induce HO-1 for up to 24 hrs, increasing mRNA for HO-1 via a HSF-1 Mechanism. This way you avoid creating more ROS-induced endothelial damage. On the other hand, topically applied ozone in the “ozone steam sauna chambers” will kill all of the MRSA and biofilm organisms on a fairly take care the skin without the need for antibiotics which would ultimately lead to antibiotic resistance. I think ozone steam Sauna therapy may be a good form of preconditioning before surgery that will reduce post-complications, especially Infections.