Scientists are exploring how Yamanaka factors can be used to partially reprogram cells without turning them into stem cells, using transient activation of Yamanaka genes for shorter timeframes than they would during full cellular reprogramming.
Researchers used SB000 and individual Yamanaka factors to induce primary HDF or lung fibroblasts from aged donors, then profiled their transcriptomes using scRNA-seq. Their studies concluded that SB000 partially reversed age-related changes in both cell types.
Stem Cells
Reprogramming allows cells to reset their genetic age through reprogramming; turning mature cells back into stem cells and then re-differentiating into different cell types; this method is called “rejuvenation” or “reversal of aging.” Specifically, Yamanaka factors are transcription factors which partially convert cells into pluripotent stem cells (iPSCs) with multilineage capabilities that may eventually form any cell in the body.
The Belmonte lab and other research groups have demonstrated that Yamanaka factors can rejuvenate specific tissues like muscles, kidneys and brain tissue in mice. Furthermore, these factors have even improved function of neurons within an optic nerve region of the brain – this phenomenon is known as Reprogramming-induced Rejuvenation (RIR).
RIR has yet to be tested in patients suffering from neurodegenerative diseases like Alzheimer’s. Researchers must ensure that the process does not trigger uncontrollable cell division that could result in tumor formation; to do this, they must identify which genes and molecules are involved. They can do this by analyzing chromatin modifications, transcription factors and DNA modifications during various types of reprogramming processes.
Yamanaka factors can have the unfortunate potential of changing cell identities so they no longer correspond with particular tissues or cell types; this creates major difficulties when used for rejuvenation therapy, as such treatment would likely require genetically engineered cells that don’t perfectly correspond with human anatomy.
Scientists have recently learned to harness Yamanaka factors more carefully, using them to partially reset skin cell identities in a more controlled fashion and replace damaged or dead ones in order to repair aging damage and restore youth. Such research provides significant steps forward towards developing anti-ageing treatments that do more than cover wrinkles with makeup.
Future scientists could develop rejuvenation treatments using Yamanaka factors combined with other genes and proteins. For instance, they could add a gene that prevents cancer caused by Yamanaka factors; additionally they might include one to allow cells to tolerate reprogramming; they might even improve efficiency by making sure only mature cells become iPSCs.
Neurons
Neurons are information messengers, transmitting electrical and chemical signals across their axons, dendrites and synapses to other neurons – responsible for everything we think, feel and do – through their axons, dendrites, synapses and synaptic connections. Their work is essential to our brain health and functioning – without it we wouldn’t be able to think, feel or move at all! These support cells known as astrocytes and oligodendrocytes’ work we wouldn’t even be alive today!
As we age, neurons gradually lose some of their ability to transmit messages and their metabolic processes become slower – both major risk factors for neurodegenerative diseases like Alzheimer’s. Recently however, scientists have demonstrated how some Yamanaka factors may reverse these changes in neurons.
Researchers behind this study focused their efforts on neurons located within the hippocampus, an area involved with memory and learning. Their team demonstrated how a cocktail of four transcription factors could restore these neurons back to functioning at levels seen in younger mice; suggesting other transcription factors may also help rejuvenate neurons and possibly other types of cells.
Not only were neurons restored through this technique, but researchers discovered that reprogrammed cells also extended lifespan in older mice. This is an astounding discovery as it suggests it may be possible to extend organism longevity by reversing aging at its source – cells.
Though partial reprogramming is an exciting field, some issues must first be addressed for it to be utilized therapeutically. One issue involves Yamanaka factors used for partial reprogramming activating pluripotency genes and increasing cell proliferation, leading to tumor-like structures known as teratomas. Furthermore, sustained OSKM expression may cause hepatic and intestinal failure in mice.
This research not only extends the lifespans of older mice, but it also shows the promise of partial cell reprogramming to rejuvenate other tissues such as skin, liver, and kidneys. A team of researchers is currently testing its effects in order to create therapies which extend lifespans and improve human health.
Muscles
Muscles are composed of cells/fibers with the sole function of contracting in order to move. Most muscles are responsible for moving bones in the skeleton; however, they also help the heart beat properly and line hollow organ walls such as the intestines and uterus linings. Most food, blood, and fluid movement in our bodies is produced through muscle contraction; Type IIb muscle tissue is generally faster and more glycolytic than other types; other muscle types include fan-shaped or triangular muscles as well as multipennate muscles which resemble feathers side by side.
Blood Cells
Harvard team researchers first demonstrated the ability of Yamanaka genes to rejuvenate cells in muscles, brain tissue and the optic nerve (which plays an essential role in vision) using long-term treatment with Yamanaka gene cocktails over long periods. Later they extended lifespan in mice suffering from premature-aging diseases through this approach and reported improved vision in monkeys receiving similar treatment over long time periods.
To test whether these factors could impact aging in other tissues, they conducted research with mice with chronic anemia, an illness which causes extreme weakness and fatigue. They discovered that using Yamanaka genes restored these red blood cell’s ability to produce hemoglobin (a protein responsible for transporting oxygen around the body). They also observed cells revert back to more youthful states as they no longer produced inflammatory molecules which contribute to inflammation elsewhere in the body.
Another type of blood cell which responded positively to Yamanaka factors was white blood cells, which are vital in helping fight infection and release substances like histamine if there is an allergic reaction. White blood cells also prevent blood clots and repair damaged tissue, according to researchers. They found that using the cocktail of Yamanaka genes reactivated these cells into more youthful states without producing inflammatory molecules which trigger autoimmune disorders like asthma.
Scientists are now developing methods of administering Yamanaka genes directly to tissues with the goal of increasing organism longevity. One option involves directly editing adult cell genomes via gene therapy systems; however, this raises ethical considerations. An alternate less invasive option involves providing cells with Yamanaka factors via DNA or mRNA delivery systems; however this has proven ineffective due to poor efficiency and insufficient organ specificity of existing delivery systems.
