Epigenetic reprogramming: the road to reversing time

Epigenetic modifications – also known as “aging clocks” – have emerged as promising markers of aging and accurate predictors of age-related diseases; they’re a hot area of investment activity.

Although extending life expectancy – Longevity – has long been associated with health, the overall increase in human life expectancy in recent decades is often accompanied by health deterioration and the occurrence of various age-related diseases, which compromise the quality of life. The past decade has seen substantial advances in the understanding of the molecular mechanisms underlying aging; however, the role of epigenetics in lifespan and healthspan has only recently come in to focus.

Longevity.Technology: Epigenetics collectively refers to phenotype-modulating mechanisms that go beyond the DNA sequence. These epigenetic mechanisms range from the addition of chemical modifiers to DNA (such as methylation) and histones (such as acetylation) – also known as epigenetic “marks” – to the regulation of mRNA stability and its translation into proteins. By turning genes on and off, these mechanisms can reversibly alter cellular and physiological phenotypic characteristics without altering the genetic sequence [1].

In 2013, Steve Horvath [2] first revealed that epigenetic modifications, and especially DNA methylation, at specific parts of the genome, are associated with aging and are, therefore, promising biomarkers of aging or “aging clocks” [3]. Since then, several efforts have been made to identify novel epigenetic clocks, with machine learning-based aging clocks (also known as “deep aging clocks”) showing considerable promise [4].

 


 

Since epigenetic modifications are reversible, epigenetic reprogramming is a promising approach to increase lifespan and healthspan.

 


 

We previously reported that Insilico spin-out Deep Longevity is collaborating with Human Longevity Inc. to deploy an extensive range of AI-powered aging clocks and shortly thereafter, Deep Longevity was acquired for US$3.79 million by Hong Kong-based Regent Pacific Group – aging clocks are fast emerging as a key Longevity investment area.

EAA: epigenetic age acceleration. Source: Wandering along the epigenetic timeline. Clin Epigenet 12, 97 (2020)

Numerous environmental factors previously linked to aging (stress, smoking, unhealthy diet, alcohol, etc.) have been shown to, at least in part, promote the development of age-related conditions by modulating aging clocks. Scientists believe that epigenetic age, based on these aging clocks, is a more accurate predictor of age-related conditions than chronological age as they are indicative of a person’s lifestyle and exposure to aging-promoting environmental factors [1].

Effects of environmental factors on aging and epigenetic reprogramming methods to counteract agin
Effects of environmental factors on aging and epigenetic reprogramming methods to counteract aging. Source: Topart, C., Werner, E. & Arimondo, P.B. Wandering along the epigenetic timeline. Clin Epigenet 12, 97 (2020).

Given the strong links between aging and epigenetic modifications, it is not surprising that the accumulation of certain epigenetic alterations and DNA methylation, in particular, during aging, have been associated with numerous age-related diseases, including cancer, chronic inflammation and Alzheimer’s disease.

 


 

… a recent clinical study by Fahy et al. … was the first to confirm the possibility of reversing aging through epigenetic reprogramming in humans.

 


 

Emerging evidence suggests that epigenetic reprogramming can actually reverse aging [1]. Notably, a recent clinical study by Fahy et al. [5] has shown that a 12-month treatment with recombinant human growth hormone decreased the epigenetic age by approximately two-and-a-half years; this landmark study was the first to confirm the possibility of reversing aging through epigenetic reprogramming in humans.

Aging clocks can provide further insight into the molecular mechanisms underlying aging required for the development of Longevity-promoting and rejuvenation interventions. Since epigenetic modifications are reversible, epigenetic reprogramming is a promising approach to increase lifespan and healthspan.

[1] https://bit.ly/31LFV7G

[2] https://pubmed.ncbi.nlm.nih.gov/24138928/

[3] https://pubmed.ncbi.nlm.nih.gov/23177740/

[4] https://www.aging-us.com/article/102475/text

[5] https://pubmed.ncbi.nlm.nih.gov/31496122/

Image by Gerd Altmann from Pixabay

Eleanor Garth
Deputy Editor Now a science and medicine journalist, Eleanor worked as a consultant for university spin-out companies and provided research support at Imperial College London and various London hospitals in a former life.

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