Epigenetic Reprogramming

This is a very interesting subject and below, I have edited parts of an article which looks at the subject of re-programming us to promote a longer, active lifespan. Research into epigenetic reprogramming is still in its infancy and looks at the erasure and remodeling of epigenetic marks (like DNA methylation and histone modifications) that alters gene expression without changing the underlying DNA sequence. It is essential for early embryonic development and cell differentiation, and is now being researched to reverse aging (rejuvenation) and treat diseases.

Perhaps not quite on the subject of skincare, but nonetheless it shows how far science has come to preserving a longer active lifespan. If you are interested in this fascinating subject, the link and citation to the original article are shown at the bottom of this post. Epigenetics studies heritable changes in gene activity that don't alter the DNA sequence itself, but rather how genes are read and expressed, like switches turning them "on" or "off". Think of it as an instruction manual that tells DNA genes what to do and when.

The pursuit for the fountain of youth has long been a fascination amongst scientists and humanity. Ageing is broadly characterised by a cellular decline with increased susceptibility to age-related diseases, being intimately associated with epigenetic modifications.

Recently, reprogramming-induced rejuvenation strategies have begun to greatly alter longevity research not only to tackle age-related defects but also to possibly reverse the cellular ageing process. Hence we highlight the major epigenetic changes during ageing and the state-of-art of the current emerging epigenetic reprogramming strategies leveraging on transcription factors. Notably, partial reprogramming enables the resetting of the ageing clock without erasing cellular identity.

Promising chemical-based rejuvenation strategies harnessing small molecules, including DNA methyltransferase (crucial for establishing and maintaining DNA methylation patterns, which regulate gene expression, genomic stability, and developmental processes) and histone deacetylase (act as epigenetic regulators, crucial for controlling cell proliferation, differentiation, and survival) inhibitors are also discussed. Moreover, in parallel to longevity interventions, the foundations of epigenetic clocks for accurate ageing assessment and evaluation of reprogramming approaches are briefly presented. Going further, with such scientific breakthroughs, we are witnessing a rise in the longevity biotech industry aiming to extend the health span and ideally achieve human rejuvenation one day.

Several studies suggest that ageing should be considered a disease, emphasizing the plasticity of the ageing process, having a potential for treatment, rather than an inevitable process. Notably, there have been many efforts to formally classify ageing as a disease, as such a step is fundamental to formally advance appropriate clinical diagnosis and longevity interventions. For instance, organ and tissue senescence-related disease codes have been proposed to be included in ageing classifications in the World Health Organization (WHO) International Classification of Diseases (ICD).

Reprogramming-induced epigenetic rejuvenation is an emerging field of research focused on countering the ageing process through the modification of epigenetic marks and gene expression patterns. Reprogramming can be carried out in different ways, namely complete reprogramming and partial reprogramming.

Overall, epigenetic reprogramming is currently the most promising strategy to be harnessed for age reversal and human rejuvenation. Notably, according to the ITOA, the loss of epigenetic information throughout someone’s life is driven by DNA breakage and repair-induced changes and this is a reversible cause of ageing.

In other words, ageing in mammals is just now beginning to be perceived as a software problem in the system, which can be easily rebooted to restore the corrupted epigenetic information from an existing backup copy. With such groundbreaking hypotheses, the manifestation of age-related diseases may one day be prevented and even reversed, which may lead to a revolutionary paradigm shift in traditional medicine. The plasticity and modulation of the epigenetic landscape play a pivotal role in the ageing process, nevertheless, such complexity is yet to be fully deciphered. Moreover, the ageing field is still in its infancy, and translating rejuvenation strategies to humans should be cautious, facing many hurdles, from long-term stability to safety and efficacy aspects to ethical and legislative considerations.

The rise of ageing research also opens the door for several ethical and social concerns that should be discussed. What does it really mean to “reverse” or “delay” ageing? Is ageing a disease? Scientific research is still in its infancy and ageing interventions should be accurately validated before clinical translation, regarding the optimal period, frequency, and suitability of interventions. Furthermore, metaphysical concerns are raised as humans seem to be trying to play Gods. Is it morally acceptable to extend human life? If ageing is an integral part of the human experience, intervening in this process may be viewed as altering the fundamental nature of what it means to be human. Cultural, social, and religious factors lead to conflicting opinions, and resolving these philosophical issues will not be easy.

As gene therapies face many hurdles regarding their safe and efficacious delivery, alternative reprogramming strategies such as the use of small molecules for chemical-based cell rejuvenation is a highly promising alternative. Notably, in the future, artificial intelligence may further speed the screening of novel compounds for mammalian age reversal. Other alternative rejuvenation approaches using young blood plasma perfusion or parabiosis have also shown favorable effects against various aged-associated diseases in mice. Notably, numerous screened blood factors can restore youthful traits, revitalise organ function, and reduce the DNA methylation age.

NOT MY OWN WORK. Taken from: (Italics here and above, are mine)

Beatriz Pereira, Francisca P. Correia, Inês A. Alves, Margarida Costa, Mariana Gameiro, Ana P. Martins, Jorge A. Saraiva, Epigenetic reprogramming as a key to reverse ageing and increase longevity, Ageing Research Reviews,

Volume 95, 2024,102204, ISSN 1568-1637, https://doi.org/10.1016/j.arr.2024.102204.

(https://www.sciencedirect.com/science/article/pii/S1568163724000229)

Copyright © 2026 by the authors.

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