A new rejuvenation technique that potentially could reverse 30 years of aging!

Aging is a natural process in which the organismal capacity and fitness decline over time, leading to tissue decline, dysfunction, and disease. The aging process is driven by mechanisms such as telomere attrition, epigenetic alterations, genetic changes, and the accumulation of abnormal proteins. The outcome of these processes is mitochondrial dysfunction, cellular senescence, and others, impacting the regenerative capacity of cells and tissues. Currently, epigenetic alterations can be measured accurately and be used to determine chronological age with high accuracy in humans, making them a valuable tool in identifying the success of the rejuvenation process.

Somatic cell reprogramming is a technique that converts most somatic cells to induced pluripotent stem cells (iPSCs) (embryonic stem cell-like state), reversing the age-related decline. This method leads to the reversal of many hallmarks of aging, like the ones mentioned above. However, this technique also leads to loss of somatic cell identity and function. Recent research has brought to light techniques that allow in vivo transient reprogramming that induces rejuvenation without losing cellular identity. However, the rejuvenation effect of transient methods reverses the aging clock for about three years compared to complete iPSC reprogramming. Here we report results from a study by Gill et al., who managed to achieve rejuvenation equivalent to about 30 years using a novel transient reprogramming strategy.

In their work, the researchers implement their technique during the maturation phase of the reprogramming process using lentivirus. This way, the aging process is reversed without losing cell identity. The reprogramming process can be divided into 3 phases, 

• the initiation phase involving somatic repression, 
• maturation phase in which partial pluripotency genes expression occurs,
• stabilization phase where complete pluripotency activation takes place. 

Using this maturation phase transient reprogramming (MPTR) method, the researchers were able to reverse the effects of aging on dermal fibroblasts from middle-aged human donors while keeping cellular identity. Their results indicated that the rejuvenation effect on the transcriptome (the protein-coding part of the genome) was about 30 years. Similarly, the reversal of epigenetic alterations, including H3K9me3 histone methylation and DNA methylation, was in the same reported range. In addition, the authors indicated that the treated fibroblasts showed levels of collagen proteins corresponding to young age.

The authors concluded that rejuvenation is possible without losing cellular identity, indicating the possibility of developing therapeutic agents targeting the aging process through the described pathway. They also indicated the need for future research to better separate cellular rejuvenation from pluripotency programs.

Source: Gill D, Parry A, Santos F, Okkenhaug H, Todd CD, Hernando-Herraez I, Stubbs TM, Milagre I, Reik W. Multi-omic rejuvenation of human cells by maturation phase transient reprogramming. eLife. 2022;11:e71624

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