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WHY COMBINATIONS OF LONGEVITY DRUGS ARE THE FUTURE

Everywhere around the world, scientists are looking for substances that can slow down aging. They are testing thousands of ingredients in laboratory animals, hoping that one of these will make them live longer.

But that is very likely not the right approach. 

Chances are small that one substance will be able to significantly slow down aging. A far better approach is to use combinations of substances. Different ingredients act on different aging mechanisms simultaneously, enabling synergistic effects, which can at times be impressive. 

Imagine that ingredient X succeeds very well in slowing down an important aging mechanism. You then would expect that this ingredient will significantly extend lifespan. But this is often not the case. After all, aging is caused by many different mechanisms, each of which contributes a small part to aging. Ingredient X may impact one aging mechanism, but then there are many other mechanisms that will still slowly kill you. 

Compare this to repairing a dilapidated house, and that you repair only the gutter. Fixing the gutter is a great idea in itself, but probably will do little to slow down the collapse of the house if you do not also repair the flooded basement, the broken windows, the crumbling walls, or the leaky sewerage.

It is not that repairing the gutter does not work. It is that if you solve one thing, there are many other things that will cause the house to eventually collapse. Repairing the gutter will only postpone the collapse a little bit longer, at best, because other mechanisms contribute their part to the inexorable decline. 

The same for our aging bodies. If you slow down one aging mechanism, usually, you will not significantly increase lifespan. However, if you tackle several aging mechanisms at the same time, you will see a much larger effect on lifespan. 

An increasing amount of scientific studies show that combining different longevity substances works much better than just administering each one separately. Strong synergistic effects can be achieved by combining different ingredients. 

In one study, three longevity drugs were examined to see if they could extend lifespan in fruit flies. These drugs were lithium (a mood-stabilizing drug), trametinib (a MEK inhibiting anti-cancer drug) and rapamycin (a mTOR inhibitor). Each substance in itself extended its life by about 11 percent. Combining two drugs extended lifespan by about 30 percent. Combining all three drugs prolonged lifespan by 48 percent compared to the untreated fruit flies (R).

Another study looked into combinations of rifampicin (an antibiotic), rapamycin (an mTOR inhibitor), psora – 4 (a potassium channel blocker), metformin (an antidiabetic drug) and allantoin (an uric acid metabolite) in the little worm C elegans. A combination of rapamycin, rifampicin and allantoin resulted in an impressive 89 percent lifespan extension. A combination of psora-4, rifampicin and allantoin even resulted in a 96 percent lifespan extension, far more than each ingredient separately (R):

 Source: Drug Synergy Slows Aging and Improves Healthspan through IGF and SREBP Lipid Signaling. Developmental Cell. T. Admasu et al.

In another study, combining valproic acid with trimethadione resulted in a considerably synergistic effect compared to using valproic acid or trimethadione alone (R).

Another study compared various ingredients like resveratrol and plant extracts to see if they could extend lifespan in yeast cells. The plant extracts were made from valerian root, Passiflora incarnata, ginkgo biloba, Salix alba, Apium graveolens, and Cimifuga racemosa. Using valerian extract or Cimicifuga racemosa extract alone each extended yeast lifespan by about 5 days, while a combination of the two extracts extended lifespan by about 12 days. Interestingly, resveratrol alone only had a relatively small effect on lifespan (achieving an increase of about 3 days), compared to Salix alba alone which increased lifespan by about 10 days. However, a combination of resveratrol with Salix alba increased lifespan by no less than 20 days, a considerable synergistic effect (R):

Source: Pairwise combinations of chemical compounds that delay yeast chronological aging through different signaling pathways display synergistic effects on the extent of aging delay. Oncotarget, P. Dakik et al.

This important principle applies not only to drugs, but also to genes. In one study, several genes were introduced into mice. Each of these genes could theoretically slow down aging. These genes were FGF21 (fibroblast growth factor 21), klotho and TGFb-R2 (transforming growth factor-b receptor 2). The combination of TGFb-R2 and FGF21, or the combination of TGFb-R2 and Klotho, resulted in synergistic effect: they significantly improved or even abrogated heart failure, renal failure, type 2 diabetes and obesity. Combination of two genes lead to an almost 60 percent increase in heart functioning in a heart failure model, a 75 percent reduction in kidney atrophy in a kidney failure model, and complete reversal of obesity and diabetes in mice that were fed a continuous high-fat diet (R).

In another study, scientists genetically modified aging-related pathways in C elegans worms, such as the TOR and insulin pathway. Only modifying the TOR pathway resulted in a lifespan increase of 30 percent. Tweaking the insulin pathway led to a 100 percent longer lifespan. However, when both the TOR and insulin pathway were modified simultaneously, lifespan was increased with 500 percent, an impressive fivefold difference (R). Dr. Jarod Rollins, co-author of the study, said the following about this: 

“The synergistic extension is wild. The effect isn’t one plus one equals two, it’s one plus one equals five. Our findings demonstrate that nothing in nature exists in a vacuum; to develop the most effective anti-aging treatments, we have to look at longevity networks rather than individual pathways.”

The longevity drug of the future will not be one drug, but a combination of drugs. Far better results can be achieved when different substances or different genetic modifications are combined. This paramount insight guides us in developing NOVOS. NOVOS contains various ingredients that target different aging pathways, enabling synergistic effects. We don’t just want to repair the gutter, we want to repair as much of the house to keep it in an excellent condition for as long as possible. 

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.