In a giant step towards conquering the relentless march of time, scientists from Harvard Medical School (HMS), the University of Maine, and the Massachusetts Institute of Technology (MIT) have unveiled a revolutionary approach to turning back the cellular clock.
This pioneering research, led by Dr David A Sinclair of HMS, has unleashed the potential to not merely slow down ageing but to reverse ageing entirely, all without the need for editing our genes.
Sinclair’s team embarked on a journey into the heart of cellular rejuvenation, wielding an ingenious technique called “EPOCH” – Epigenetic Programming of Cellular Heterogeneity. This methodology holds the promise to breathe new life into ageing cells, resurrecting their vitality while preserving their intrinsic characteristics.
“Until recently, the best we could do was slow ageing. New discoveries suggest we can now reverse ageing,” said Sinclair, a professor in the Department of Genetics and co-director of the Paul F Glenn Center for Biology of Aging Research at HMS.
Tuning the epigenome
The very essence of this groundbreaking research hinges on the duality of information storage within our cells: the genome, our genetic blueprint, and the epigenome, the conductor orchestrating gene behaviour.
While the genome remains largely stable throughout our lifespan, the epigenome, influenced by the environment and the passage of time, undergoes constant flux. As we age, this epigenetic symphony often unravels, causing cellular dysfunction and facilitating the onset of age-related maladies.
In the study, the researchers scrutinised a multitude of ageing hallmarks contributing to cellular decline. Among these, the loss of epigenetic information emerged as a linchpin in the ageing process.
They explained that with age, these epigenetic instructions can become muddled or lost entirely, triggering malfunctions in the cellular powerhouse (mitochondria), provoking inflammation, and disrupting the proper division of cells. This not only expedites the ageing process but also heightens the vulnerability to ailments like macular degeneration, hypertension, and metabolic disorders.
Cooking up chemical cocktails
Knowing this, the scientists then began testing specific chemical compounds’ influence on the ageing trajectory. Human fibroblast cells, culled from individuals spanning various age brackets, including those afflicted by conditions that prematurely age cells, is what they used to validate their experiments.
Some fibroblast cells were intentionally encouraged to cease dividing, permitting them to age gracefully, while others underwent genetic modifications to render them resistant to change. Then these cells were given minuscule quantities of the chemical elixirs.
“The molecules included in these cocktails have been independently tested in other studies involving mice and animals,” said Dr Shefali Sabharanjak, Head of Science and Research at Serotonin Labs Inc., Bengaluru.
To delve even deeper, cutting-edge imaging tools were pressed into service to decode the cellular response to these chemicals. The aim was to illuminate the influence of these compounds on the ageing journey within cells, spanning both natural and genetically modified cohorts.
“It is most likely that these cocktails will increase health span as well as lifespan,” asserted Dr Sabharanjak.
The Yamanaka factor
This pioneering research builds upon the legacy of Shinya Yamanaka, a Nobel laureate, celebrated for his groundbreaking discovery of cellular reprogramming using Yamanaka factors. However, the current study introduces a twist: it seeks to rejuvenate human cells devoid of genetic tinkering, relying instead on chemical concoctions.
This novel approach showed some potential advantages over genetic reprogramming, sidestepping direct DNA alterations and thus offering a promising avenue for cell rejuvenation. The six chemical elixirs were seen to be capable of restoring youthful cellular characteristics and effectively reversing ageing within a mere week, all while safeguarding cellular identity.
These chemicals are reported to achieve rejuvenation to a similar extent as the Yamanaka factors, which had previously demonstrated their age-reversing prowess in certain tissues of mice but were seen as problematic due to genetic changes causing cells to become cancerous.
The published results are absolutely fascinating! Nevertheless, as Dr Sabharanjak cautioned, “It remains to be seen whether similar effects can be achieved in organoids and other higher-order physiological systems, and the safety of the complete cocktail will need to be re-evaluated in further studies.”
The implications of this research are nothing short of monumental. The EPOCH method, if seamlessly translated into a practical implementable tool without unforeseen side effects, holds the potential to be a transformative anti-ageing approach.
From a scientific standpoint, the results unveiled in this study are nothing short of awe-inspiring. Yet, as experts advise, the journey to a deployable strategy remains a path paved with unknowns, awaiting further development and refinement.
