Chemically Induced Reprogramming to Reverse Cellular Aging – Why This Headline is Phony

David Sinclair is a popular media darling for a reason, and it’s not because of great science. Rather, the reason is what philosopher, Dr. Harry G. Frankfurt, Ph.D., called bullshit.

David Sinclair at Harvard has claimed to have used a cocktail of chemicals to reverse aging. He hasn’t. Let’s see why he hasn’t. In his study, he isolated human fibroblasts, a type of mesenchymal progenitor cell that occurs throughout much of the human body, including the skin where they can easily be obtained as biopsied donor tissue. The cells were then either fed a cocktail in one group versus another group that didn’t receive the cocktail. So the comparator group was essentially given nothing – it’s a so-called placebo control. In the so-called placebo group you basically do nothing other than the standard procedure to help out the cells. It’s similar to a placebo controlled clinical trial where you compare a “heart medication” to a group where individuals who are obese and eat a horrible diet do nothing to correct their ill health. Imagine comparing the drug to obese, poor-eating individuals who start eating a great diet and lose weight during the trial. Which group, the drugged group or the healthy lifestyle group, would have the better improved outcomes? Answer: those eating better and losing weight. So Sinclair in his study doesn’t do anything in the comparator group to make the cells healthy. Many nutrients can make cells in culture have better longevity, including the commercial supplement PowerFeed A from Lonza. Shall we start an infomercial campaign for drinking PowerFeed A from Lonza to induce longevity? I think not. That would be as absurd as what Sinclair is feeding the hysterical mass media.

But what was Sinclair measuring, longevity? No. He wasn’t. He was measuring transcripts from the fibroblasts, i.e. RNA. Disease and longevity are a function of proteins, not RNA. Environmental insults are the cause of about 90% of diseases, and these environmental insults act predominantly on proteins, including brain diseases. And just because your RNA profile demonstrates a “better longevity profile” after the cocktail doesn’t mean your proteins will demonstrate a better longevity profile. They won’t, or at least, many won’t. Many proteins in the body are long-lived, including in our mitochondria, meaning once the protein is made you’re stuck with it for years, or decades, or even throughout most of your life. Transcripts don’t mean diddly for long lived proteins because your not replacing those proteins. Even when the protein is made through transcription-translation, the protein will be further modified through post-translational modifications. And post-translational modifications are a big factor in aging. Environmental factors can destroy the function of proteins, doing so through post-translational modifications. One simple example is the glycation of collagen fibrils in the human body, increasing the odds of cancer, diabetes, dementia, and old looking, poorly functioning skin. It’s complex, but basically proteins become glycated through interactions with too much sugar, including though dietary sugars. Glycated proteins in the extracellular matrix of the skin and blood vessels, for example, become less sensitive to proteolysis. Thus glycated collagen fibers within the arterial wall become resistant to remodeling enzymes. As a result, these proteins accumulate, irreversibly thickening the vessel wall. Again, transcripts don’t mean diddly for glycated proteins because you’re not replacing those proteins. If you want to learn some of the things you can do to reduce glycation to improve healthspan and possibly lifespan, read here.

Another big problem with Sinclair’s work is the total absence of considering intrinsically disordered proteins (IDPs). These are proteins that lack 3-dimensional structure, are easily modifiable, whose function depends on the protein’s surroundings, and that account for about a third of all proteins in the body. These proteins are characterized by their low content of bulky hydrophobic amino acids. They are smaller and more pliable than their globular 3-dimensional counterparts, and therefore much more free to operate as a function of their environment. Thus, our exposome likely affects the IDPs, and mRNA transcript characterization would mean little to how the IDP is functioning.

Others have written about David Sinclair’s propensity for bullshit, money, and bad science, and it’s sad this guy gives science and scientists a bad name through the echo chambers of a poorly engaged mass media peddling his phony science. When talking about Sinclair’s work, fellow molecular biologist at Harvard, Dr. Gary Ruvkun, Ph.D,, has said, “Don’t believe anything you’ve heard.” Basically, we’re talking about more BS from US medical schools, funded by the National Institutes of Health, which is run by physicians, such as Francis Collins, with a propensity for bullshit (the genome will predict all diseases) and fraud. The field is besieged by “medical fakery” as exemplified by phony clinical trials. And then this fakery is sold by practicing physicians who act as technical sales reps for the drug companies. Making this fakery even is worse, is that drug companies pay physicians to sell their drugs using physicians who don’t what they’re doing and/or commit malpractice. The medical industry is often perverse and driven by a desire for power, fame, and money (Sacklers are an example of such physicians), and many people are suffering as a result. This is a world-wide phenomenon, from the halls of Harvard, to medical practices in Texas, to academic physicians in Italy, it’s pervasive. Over half of FDA approved drugs don’t work, industry knows it and in a major conflict of interest, funds 3/4 of the FDA budget of the division that regulates drugs, and David Sinclair’s work is not helping to bring forth therapeutics that work.