The key elements of a strategy for age reversal are emerging in the recent literature –we call it YOUNGING1.0.  This blog entry describes our understanding of that strategy, its elements, how it works and its results, and cites research evidence for its salient aspects.  This is possibly the most important blog entry published over the 12-year history of ANTI-AGINGFIREWALLS.  That is because such a strategy – where human physiological age is actually and significantly reversed –once demonstrated will be unique in our history of all humanity.  Age reversal has happened in stories and myths, such as the story of Dr. Faustus and vampire myths, and the power of Fountains of Youths, a number of which can be visited in the world today.  Vince first visited the Fountain of Youth Archeological park in Saint Augustine Florida when he was only 4, and has since visited others including the Fontana di Trevi in Italy, the Baños de Coamo in Puerto Rico and. Tambomachay in Peru.

But though much sought after, true YOUNGING approaches have never existed as the result of an actual scientific intervention.  We seek here to lay out the elements of a science-based age reversal strategy, one that works in small animals which we believe will work in humans as well, and one that is actionable now.  We draw those elements from studies by numerous specialized researchers, many of whom are unfamiliar with the work of the others.  So, we are seeking to fit together pieces of knowledge from separate sources to constitute a whole new framework.  This characterization of YOUNGING is as complete as we can make it now, and we believe it to be compelling.  True, major gaps in our knowledge are still to be filled in.   We proceed first in this Section I by listing key assertions without digressing into the backup science and literature, and in Section II back up our key points with additional information, research literature sources and citations, and identify some important still-unanswered questions.

YOUNGING is real. It has been demonstrated in small animals and by much research which characterize and validate its details.

The evidence is strong that YOUNGING will work in humans. It has been demonstrated to work in rats(ref).  Of course, all statements we make here with respect to human YOUNGING are conjectural until it is actually demonstrated by well designed clinical studies.  However, the genetic and epigenetic compositions of humans and rats and associated pathways and process in humans (and in fact of all mammals) are so evolutionarily conserved and nearly identical, that we assign a high degree of certainty to the basic points made here.  The research literature citations in Section II associated with each of these points convey why we are so certain.

YOUNGING is the result of an epigenetic program. In this respect it is a program like aging itself, running the aging clock backwards.  You can think of it as a program or subroutine that replaces or runs simultaneously with the aging program itself.  We have good ideas about the nature of one such program we call YOUNGING1.0, how to trigger its activation, how it works, how long it runs, and what its biological youth-generating results can be.

There are many seemingly practical approaches to demethylating H3K27me2/3 and thus to initiate the YOUNGING.  The main substance that specifically demethylates H3K27me2/3 is JMJD3.  The Jumonji domain-containing protein D3 (JMJD3), specifically demethylates di- and trimethyl-lysine 27 on histone H3 (H3K27me2/3).  So we can ask “what substances can we practically use to activate JMJD3 and what other substances cab be used to demethylate H3K27me2/3?  It turns out the list of familiar substances that can do that is quite long, including:

Certain familiar herbal substances, including Curcumin, and High AkBA Boswellia

DHEA

Alpha keto-gluterate

Vitamin D

and dozens of others to various extents

And also processes such as fasting and breathing supplemental oxygen

Nicotinamide riboside, the mitochondrial UPR response and extending mammalian longevity

The 2016 publication NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice is among those reporting on this issue.  “Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging.  We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD(+) precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice.  NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmd(mdx)/J) mouse model of muscular dystrophy.  We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span.  Strategies that conserve cellular NAD(+) may reprogram dysfunctional SCs and improve life span in mammals.”