How to Reverse Aging in Mice
Researchers are investigating ways to reverse the aging process using chemical treatments to reprogram cells into younger states.
This caused epigenetic factors to become distracted from their usual task of gene regulation, leading to older-looking mice with elevated biomarkers of aging.
Epigenetics
Scientists long believed that aging was caused primarily by changes to DNA. Mutations prevent genes from working effectively, eventually resulting in cells ceasing to function altogether and leading to tissue and organ failure, disease and even death. But more recent research indicates there may be more to aging than mutations; epigenetic changes also play a part in its progression.
Epigenetics plays an essential role, since DNA serves as the blueprint of life, yet doesn’t always dictate how cells express or fulfill their function. Instead, epigenetics acts like an operating system by controlling which genes are activated or not activated and when. Thus different cell types appear and behave differently even though they share identical DNA.
Researchers wanted to see whether an epigenetic breakdown contributed to aging by creating temporary but fast-healing cuts in lab mice’s DNA. These temporary cuts simulated low-grade but ongoing DNA damage sustained daily due to activities like breathing, exposure to sunlight and cosmic rays, contact with certain chemicals etc. They observed that when these mice’s epigenetics became disrupted they started aging more rapidly – their cells lost identities such as skin or muscle cells and biomarkers of aging appeared within their bodies more rapidly.
Scientists then used gene therapy on mice to reverse epigenetic changes, returning them back to a youthful state and reversing epigenetic changes caused by epigenetic stressors. As a result, they once again showed the ability to regenerate tissues and heal themselves; experiments are being done now with expanding this treatment approach to other mammals.
No one knows yet whether this technique would work on humans. While increasing telomerase levels could lengthen lifespan, doing so also raises cancer risks; so scientists would need to find safer means of slowing or reversing human aging. If successful, however, the research could eventually lead to treatments allowing millions in developing nations who cannot afford costly longevity clinics to live longer healthier lives.
Cellular Rejuvenation
Cellular rejuvenation is the practice of altering cells’ genetic make-up to restore their youthfulness, through alteration. There are various methods available, but most therapies involving cellular reprogramming use epigenetics to reset internal clocks allowing cells to function like before becoming damaged, potentially stopping or even reversing signs of aging such as oxidative stress, inflammation and DNA mutations that contribute to this process.
Harvard scientists led by Professor Yanagihara have demonstrated how it is possible to reverse cell aging without leading to uncontrollable cell growth, through virally injecting specific Yamanaka genes into cells. Results are promising: improved vision and extended lifespan in mice are reported while this research may lead to therapies for various diseases.
Researchers tested several chemical cocktails for their ability to reset internal clocks and rejuvenate senescent cells. All identified cocktails reduced estimated ages of these senescent cells by several years. They also lowered expression of genes associated with aging while upregulating those associated with younger cells; this led to a decrease in metabolic activity. NAD+ (nicotinamide adenine dinucleotide), an essential coenzyme which couples with enzymes to perform essential body functions, was the most successful cocktail. As people age, however, NAD+ levels decrease leading to signs of aging such as wrinkles, reduced cognition, and poorer sleep quality.
Researchers employed an experimental strategy wherein they temporarily exposed senescent muscle cells to proteins required for embryonic development, partially reprogramming them as more stem-like but without altering somatic identity. After assessing whether rejuvenation had taken place, all cells had lower transcriptional age estimates and down-regulated age-associated genes, providing evidence of true rejuvenation.
Cellular rejuvenation therapy can bring many advantages to people of all ages. It can reduce fine lines and wrinkles, increase skin radiance, and boost overall health – but be patient as this process takes time – it could take weeks or even months before seeing visible results! For best results it is advised to seek advice from healthcare providers prior to beginning any cellular rejuvenation treatment therapy program.
Reactivation of Telomerase
Human cells’ telomeres become shorter with each division. If they become too short, the cell will either cease dividing or self-destruct – a process known as cellular senescence. Researchers are developing strategies to combat senescence and extend lifespan by activating telomerase. Telomerase’s two components – an RNA component providing templates for creating new telomeric DNA, and a catalytic protein that adds new telomeric DNA each time the cycle repeats – help it perform this crucial function. Reactivating telomerase may increase cancer risks; therefore, researchers have been exploring other strategies for lengthening telomeres such as increasing TERT gene copy number or overexpressing oncogenes such as c-Myc that can bind its promoter and promote transcription; alternative splicing or using TERT alternative transcript variants may all work better as ways of expanding them.
Harvard Medical School researchers recently achieved rejuvenation of senescent mouse retinal ganglion cells using four main Yamanaka factors administered through a harmless virus. Next, these cells were exposed to a chemical cocktail mimicking reactivating telomerase activity which included NAD+ precursor molecules like NMN which can increase SIRT1 activity which helps cells resist senescence and preserve telomere integrity.
The team also found that activating telomerase extended mice’ lifespans slightly; however, this didn’t translate into any change in average lifespan, suggesting it is too soon to say whether this approach would significantly extend human lifespan.
Research like this underscores aging as something reversible rather than something inevitable; however, some longevity experts remain wary. Dr. Luigi Fontana of Harvard Health and Wellness Center cautioned MNT that while he found this study intriguing, it does not prove there is one magical pill for longevity; rather it indicates that mitochondria and oxidative stress play major roles in determining life span – areas he would like to see further study on in future research studies.
Safety
Though humans have dreamt of finding the Fountain of Youth for centuries, science may finally be getting closer. According to a Harvard research team’s study published in Aging Journal, they successfully reversed aging in mice by rejuvenating their cells – something which may pave the way to treatments for heart disease and Alzheimer’s diseases among others.
Research undertaken by Sinclair’s team centers around altering how genes are switched on or off and folded into cells’ nuclei; this process, known as epigenetics, can be severely compromised by factors like pollution, environmental toxins, smoking, an unhealthy diet and chronic stress. They have developed a chemical reprogramming method which resets gene activity within cells to restore youthful functions; their method has already been tried out on mice before moving on to primates for testing.
Scientists used this approach to discover that six cocktail combinations of small molecules could restore cells back to their embryonic state, thus reversing aging and cancer development. These cocktails consist of compounds that make cells act like stem cells with the ability to form into any type of cell within the body.
To evaluate their cocktail’s effects, the team used noninvasive tests that evaluate frailty in mice. Results demonstrated that treatment reduced biological aging by one year while also improving health in these animals. Furthermore, nuclear compartmentalization tests accurately predict a mouse’s biological age.
The scientists also employed a tool known as a transcription-based aging clock to track gene activity. Their cocktails increased expression of genes involved in making blood vessels; shrinkage of such vessels is thought to play an integral role in aging as it reduces oxygen and nutrients reaching vital organs.
