Researchers at the Salk Institute have extended the lives of mice and improved their muscle and organ function. This was achieved by resetting their cellular clocks.
This is done by adding a mixture of four reprogramming genes to cells. These reprogramming genes prevent telomeres from becoming too short.
Moreover, this treatment also reversed aging in blood cells and reduced the oxidative stress they generate. It also boosted brain cell growth and improved the mice’s memory.
Reversing aging in mice is possible
A team of researchers has turned back the clock on aging in mice by using gene therapy to lengthen their telomeres. This slowed their cellular degeneration and prevented age-related diseases, such as infertility and brain impairments. In addition to its regenerative properties, the treatment also increased the mice’s brain cell growth and improved their performance in memory tests. This study is the first time that reversing aging in mice has been achieved through cell reprogramming.
Previous studies, such as heterochronic parabiosis, have shown that exposing older animals to young blood can improve their health and organ function, but it was unclear whether this improvement represents rejuvenation or simply a response to the more youthful environment. Recent studies have begun to leverage epigenetic clocks and IgG glycans, both of which indicate a person’s biological age, as a more reliable marker of rejuvenation.
Scientists have discovered that a protein called TERT, which binds to the ends of chromosomes, can help maintain telomere length and inhibit a process known as cellular senescence. This is a zombie-like state that more cells enter as they become damaged, triggering damaging inflammation and causing the organism to age prematurely. By switching off the TERT gene, scientists can slow or even reverse aging in the mice.
The method involves reprogramming cells
Reprogramming cells is a powerful tool that can produce specialized cell types for various applications, including tissue engineering and disease modeling. The process involves transforming somatic cells into pluripotent stem cells, which have the ability to differentiate into any cell type. Cell reprogramming is accomplished by inducing the expression of specific transcription factors, which triggers endogenous expression of appropriate lineage-specific genes. However, there are some limitations to this technique. For example, reprogramming may not result in the retracing of all prior differentiation intermediates, and some genes are more important than others for maintaining the desired endpoint phenotype (Figure 33.1(A)).
In recent years, scientists have made great progress in reprogramming adult somatic cells into induced pluripotent stem cells (iPSCs). These cells can be obtained from a patient with a genetic disease and are therefore useful for studying complex diseases in the lab. However, reprogramming is a difficult task and can be time-consuming, particularly when using lentiviral vectors to deliver the reprogramming factors. A new method that uses small molecules instead of gene-delivering viruses to achieve reprogramming could be much faster and more cost-effective.
Scientists have found that reprogramming mature cells can improve function in organs of old mice by extending the lifespan of these animals. This is because the reprogrammed cells can replace older ones and slow down the natural pace of aging. Scientists have discovered that the protein TERT is a critical factor in this process. By blocking TERT activity, researchers can make cells age more slowly by preventing the premature degradation of telomeres.
Reprogramming has been a challenging field for many reasons, but the most serious issue is that the rate of conversion is low. Only about one in 1,000 mature cells is successfully reprogrammed. This is despite the fact that a large number of different factors are used in the reprogramming process. HSCI Principal Faculty member Konrad Hochedlinger and his team have developed two ways to increase the odds of success by using more efficient reprogramming factors.
In their study, Hochedlinger and his colleagues demonstrated direct reprogramming of mature somatic cells to nephron progenitor cells using a cocktail of six transcription factors. They also showed that reprogrammed cells can differentiate into mature kidney cells in culture. In addition, they showed that direct reprogramming of non-myocytes into induced cardiomyocytes improves heart function in myocardial infarction mice.
It is safe
Researchers genetically manipulated mice to age faster than normal and then used gene therapy to lengthen telomeres. This reversed their aging symptoms and improved brain function. In their study, the scientists increased the activity of a gene called TERT, which normally dwindles with age. This reduced senescence in blood cells and boosted a key molecule that promotes cell growth in the brain. The results are similar to findings from studies of epigenetic clocks and glycans, such as those found in human immunoglobulin G (IgG). The research is safe, and the scientists say it could eventually be applied to humans. 32.
It is effective
Scientists at the Salk Institute have partially reversed aging in middle-aged and elderly mice by changing their cells’ activity levels. This breakthrough could help us live healthier lives, free of age-related diseases. The key is in the activity level of genes, which can be controlled by a group of molecules called transcription factors. Changing the activity of these genes can alter the way a person looks and feels.
The scientists in this study used a compound called NAD+ to turn back the clock. They put drops of it into the water of the mice and saw that their muscles became younger, and DNA damage repaired itself more quickly. In addition, they found that the mice had improved cardiovascular and neurological function. They also had less fat buildup and better glucose tolerance. The researchers have now published their findings in the journal Cell.
NAD+ is a powerful antioxidant that protects genes from DNA damage. It is found in many foods, including avocados, broccoli, and edamame. It is a key player in the body’s energy production and has been linked to a reduced risk of dementia and heart disease. Increasing NAD+ in the body may prevent the effects of aging, and researchers hope to one day apply this approach to humans.
In a previous experiment, the same team genetically manipulated mice to age faster and then gave them gene therapy to extend their telomeres. The telomeres are the ends of a strand of DNA, and when they become too short, they cause cells to stop dividing. The mice in the study had longer telomeres after treatment, and they looked and acted like young mice. They also had lower biomarkers for aging, such as brain size and infertility.
While these results suggest that it is possible to slow and even reverse aging, it remains unclear whether this improvement signifies genuine rejuvenation. For example, clinical biomarkers like telomere length and IgG glycans do not reliably indicate fundamental cellular changes. It is also crucial to determine whether the plasma fraction treatment actually turned back epigenetic aging in these animals.