The suggestions in my Anti-Aging Firewalls treatise, for following certain lifestyle patterns and taking certain supplements for longevity, are based on scientific research rather than simply on folk remedy lore or conventional wisdom. But what is the nature of this scientific research on which I base my suggestions? It can be of several different kinds, including:
1. Macroscopic studies of large populations. These studies involve looking for correlations among selected factors. An example is a study of centenarians on Okinawa, an island where an unusual number of people live a long time. This study of some 900 centenarians, their families and control groups helped identify specific genes and gene polymorphisms that appear to contribute to longevity as well as contributing lifestyle factors, including eating relatively few calories, exercising and not smoking or consuming alcohol. And of course in Okinawa people eat lots of fish and drink green tea. These studies can reveal interesting correlations and clues. For example, the Okinawa study established that the centenarians studied have genetic polymorphisms that place them at lower risk for inflammatory and autoimmune diseases.
2. Large population cohort studies. These are studies that follow coherts of thousands, tens of thousands or even hundreds of thousands of people over 10-20 or longer year periods, like the Woman’s Health Initiative or the Framingham Heart Study or the Bogalusa Heart Study. Again, they look for correlations such as the effect of smoking or being overweight on cancer incidence or longevity. These studies have been particularly useful for establishing the validity of conventional wisdom as related to longevity, such as clearly documenting the effect of having a positive mental attitude on longevity.
3. Controlled clinical trials. These are carefully controlled double-blind studies typically pursued for drug certification that proceed in phases. They may typically involve anywhere from a few dozen to thousands of carefully selected people over a test periods of several months for the final phase. They are usually very narrowly focused and yield limited information with respect to longevity. For example, a list of clinical trials for patients diagnosed with gliablastoma, an incurable brain disease, can be found here. These trials are very specific with respect to substance being tested, patient conditions and their relationship to other therapies. Clinical trials typically cost tens or hundreds of millions of dollars so there is no incentive for a drug company to study a promising natural substance that is in the public domain. Also, for longevity purposes, a six-month study is not likely to tell much. If we wanted to test some kind of longevity concoction that we thought would double human lifespans, a clinical trial would have to be run for 40-100 years to yield meaningful results.
4. Animal experiments. Mice and rats are genetically very similar to humans but live only 2-3 years, so are excellent subjects for longevity-related experiments. The studies can be quite technical. Here is an example relevant to the cell nuclear factor NF-kappaB known to be relevant to human longevity: Maintenance of NF-ÎºB Activation in T-Lymphocytes and a Naive T-Cell Population in Autoimmune-Prone (NZB/NZW)F1 Mice by Feeding a Food-Restricted Diet Enriched with n-3 Fatty Acids We know of several approaches that can extend the normal lifespan of mice by 30% to 50% We are not sure how many of these approaches will scale-up to work for humans but these experiments are providing valuable clues and are a source of optimism for longevity aficionados like me.
5. In-vitro and in-vivo studies of cell populations. There is a great numer of experimental studies going on that look at specific cell populations under particular conditions that that have a bearing on longevity. For example, many such studies look at neurogenesis and adult stem cell differentiation as impacted by specific gene activation cascades and particular proteins, or as stimulated by certain dietary substances. These studies can yield specific nuggets of insight such as the roles of key proteins and activation factors like INK4a, P-53, and NF-kappaB. Again, there are very many of these studies and they can be quite technical each yielding a single piece of the immense longevity puzzle. An example related to eating pigmented fruits is A dietary anthocyanidin delphinidin induces apoptosis of human prostate cancer PC3 cells in vitro and in vivo: involvement of nuclear factor-kappaB signaling.
6. Synthesis and review studies. These are studies that consider results together from possibly many experiments and look at them in terms of the powerful forefront areas of genetics, cell signaling cascades, gene activation, genomics and epigenomics. They also draw on knowledge from related areas, such as computational genomics, epigenomic and protein-folding databases. Some of these studies are starting to link gene expression factors to longevity, such as in We have identified various signaling cascades directly related to longevity such as the Insulin Growth Factor 1 axis. This axis seems to be the one that is involved in achieving longevity via calorie restriction. And it also seems to be activated by taking the supplement resveratrol.
All the actions and supplements in the anti-aging firewalls are based on one or more of these kinds of research. Most are supported by several of these kinds of research and, for a few firewall elements, supporting research exists on all of the above levels. For example, the value of green tea as a cancer preventative is established on all of the above levels as is the value of regular hard exercise for longevity in general.
It is clear that radical life extension—to beyond age 110—must depend on knowledge associated with the newer and more sophisticated ongoing studies in epigenetics, molecular biology, and medical research. Research suggests that certain substances already in the anti-aging regimen may act powerfully toward this end, but what they can actually do for human life extension will not be clearly known for many years. These substances include:
– Use of r-alpha lipoic acid and acytl-l-carnitine to address cell mitochondrial longevity and inhibit unwanted cell apoptosis (self-destruction).
– Use of resveratrol or resveratrol homologs to activate the SIRT1 and FOXO3 “longevity” genetic pathway, the pathway known to confer life extension due to calorie restriction
.– Use of astragaloside IV or cycloastragenol to activate telomerase expression in body cells, possibly immortalizing these cells and conferring longevity to the associated organs.
.– Use of combinations of green tea, curcumin, and other phyto-substances for their powerful cancer-preventative effects and cardiovascular benefits that operate through genetic mechanisms.
Longevity research is a ride into uncharted territory. The ride is moving faster and faster and I believe we will see breaking the 120-year ultimate human age limit in my lifetime. As a matter of fact, I am planning to be one of the breakers.