WSU researchers conducted their experiment by activating four genes known as Yamanaka factors that promote rejuvenation in damaged cells into stem cells, thus rejuvenating muscles and pancreas of mice.
MiR-302b treatment greatly enhanced external appearance and grip strength in aged mice without increasing tumor or disease burdens, as well as reversing its decrease. Furthermore, its delivery restored proliferative capacity within liver and skin tissues of aged animals.
Epigenetics
An international team has reversed aging in mice by restoring the integrity of their DNA’s epigenetic pattern rather than changing genetic code itself. Their findings, published in Cell, demonstrate how loss of epigenetic information leads to signs of aging in mice; resetting their epigenetic clock can reverse it and reverse these signs of aging.
Researchers used temporary, fast-healing cuts in the DNA of lab mice to simulate low-grade, ongoing breaks that mammalian cells experience from daily activities like breathing, exposure to sunlight or cosmic rays and certain chemicals, or contact with certain substances. As these cuts induced changes to epigenetic patterns of their DNA, and as these epigenetic changes accumulated they caused biomarkers of aging in these mice to increase significantly; using recently developed tools researchers measured biological age rather than chronological age and discovered it was higher compared to mice without cuts.
Next, scientists administered gene therapy that restored their damaged epigenetics back to their younger states – with dramatic results. “The effect was comparable to rebooting a computer that had become dysfunctional,” according to Sinclair. All organs and tissues of mice returned to functioning normally once again.
Epigenetic reprogramming entails chemical modifications to DNA that switch genes on and off, with long-term impacts that determine their rate of revival after being switched off by cells. Lifestyle and environmental factors, including air pollution, poor diet, psychosocial stress, exercise, pharmacological treatments (like HDAC inhibitors and senolytics), as well as medications (like HDAC inhibitors or senolytics), all affect epigenetic aging – this process known as epigenetic aging; studies show it can be reversed using various interventions, lifestyle interventions, supplements, medications/pharmacological treatments/ pharmacological treatments as well as gene therapy strategies.
Reversing epigenetic aging can be accomplished using lifestyle and pharmaceutical approaches, or by reprogramming cells into pluripotency using Yamanaka factors. The ICE technique offers another solution by bypassing pluripotency altogether and targeting specific genes involved with aging directly. It has the potential to reduce aging more quickly in humans than most mice since signs of aging usually appear earlier than expected; providing for an earlier rejuvenation window while still giving enough time for normal functioning to resume after change occurs.
DNA Repair
The genome is constantly exposed to DNA damage from environmental hazards like oxidative stress, genotoxic chemicals and radiation as well as endogenous factors like replication errors or spontaneous hydrolysis reactions, or endogenous factors like replication errors or spontaneous hydrolysis reactions. Such damage may lead to mutations which disrupt cell functions leading to premature cell senescence or even eventual cell death [1].
Scientists long held the view that DNA mutations were one of the main drivers of aging; however, more recent research has demonstrated other sources of genomic instability also contribute significantly to it – such as shortening of telomeres, replication errors and mitochondrial dysfunctions – while degradation of proteins within cytoplasm and DNA damage caused by UV light exposure or reactive oxygen species are significant contributors as well.
Researchers have researched various approaches for increasing lifespan by strengthening DNA repair mechanisms, such as mismatch repair (MMR), error-prone nick repair (ER), and non-homologous end joining (NHEJ).
All these mechanisms require significant amounts of energy in the form of NAD+ or NADP+ coenzyme coenzymes that become depleted as we age. Sinclair and his colleagues were able to address this problem by developing a drug containing the precursor for NAD+ called Nicotinamide Mononucleotide or NMN that gave older mice access to its precursor and kickstarted their DNA repair process and even reverse existing damage, producing indistinguishable animals from younger counterparts.
Sinclair and his team are currently hard at work translating their discovery to human patients, working towards creating a daily pill to promote the cellular repair mechanism and protect against future DNA damage. If all goes according to plan, testing of this new compound in humans should begin later this year – if its effects prove positive then therapy could delay age-related diseases while improving quality of life overall – ultimately increasing lifespan by 10 years in total! It would mark a monumental step forward against cancer and cardiovascular diseases among others.
Yamanaka Factors
Yamanaka Factors (Oct3/4, Sox2, Klf4 and c-Myc) can reprogram adult cells into pluripotent stem cells (iPSCs). When allowed to mature into certain cell types, iPSCs can be used for drug discovery as well as studies into human development, which could revolutionize how we perceive aging research as well as rejuvenate ourselves over time. This work could change both how aging research progresses as well as our biological age and rejuvenation strategies.
Scientists had long assumed that egg cells contained a complex array of factors capable of returning somatic cells back to embryonic status and making them suitable for rebirth as new blood, skin or heart cells. Takahashi and Yamanaka’s discovery that just four factors could reprogram mature cells into iPSCs revolutionized cellular reprogramming research.
Researchers have long understood how to manipulate Yamanaka factors to create various combinations of iPSCs. For instance, adding stemness-promoting genes, like NANOG and LIN28 can increase efficiency when it comes to reprogramming cells; additionally removing one such as c-Myc can decrease risk for cancerous cell development.
Utilizing their knowledge, scientists were able to optimize the reprogramming process by combining and screening different sets of reagents that would increase formation of iPSCs. A team led by postdoctoral researcher Ori Bar-Nur and including Professor Hochedlinger discovered that using both classic Yamanaka factors as well as two smaller molecules (ascorbic acid and CHIR-99021) together is capable of creating highly effective iPSCs in mouse cells.
These iPSCs were then programmed into aged mice, where they proved capable of rejuvenating both muscles and brains of these animals. A uniformly accelerated rotarod test demonstrated this, with Exos-aging mice staying on longer than PBS ones even at 30 months of age! Furthermore, Exos animals also performed better in water maze tests, spending less time searching for their platform.
However, as of 2023 we have learned that full reprogramming of adult cells to iPSCs may not be optimal for rejuvenation as the resultant cells no longer bear their original identities – like Brad Pitt in “The Curious Case of Benjamin Button.” Instead, researchers want the ability to partially reprogram adult cells so they maintain their identities while rejuvenating themselves effectively.
Cellular Rejuvenation
Researchers are investigating cellular rejuvenation therapies as a way of combatting the aging process by restoring damaged or aged cells’ functionality. Therapies involve multiple approaches including cellular reprogramming, gene editing and stem cell therapy. Rejuvenation therapies require multidisciplinary collaborations as well as innovative research technologies like machine learning (ML) to speed development and evaluation processes for rejuvenation strategies.
ML technology can be used to identify and assess molecular signatures of aging processes at the single-cell level, providing insight into patterns and trends difficult to discern with traditional methodologies. Furthermore, this technique could facilitate novel therapies as well as predict cellular rejuvenation responses more accurately than before.
Another promising method for rejuvenating cells is using induced pluripotent stem cells (iPSCs). These versatile cells can transform into any tissue type, making them suitable candidates for regenerative medicine and immune rejection prevention. Furthermore, iPSCs can even be created from patient’s own cells to eliminate risk altogether and regenerate specialized transplantable cells to restore damaged tissues’ functionality.
Rejuvenating the body through removal of senescent cells is currently being explored, though researchers must tread carefully as certain senescent cells may play essential roles in wound healing and other vital processes. Senolytic drugs can be developed that specifically target these senescent cells with minimal impact on healthy tissues.
Scientists have demonstrated that resetting a cell’s genome can delay biological aging. This can be achieved through methods such as telomere elongation, DNA repair and renewal, epigenetic modifications, mitosis/cell division stimulation stimulation mitophagy maintenance. Resetting one’s genomic may reduce oxidative stress while increasing protein production as well as maintaining mitochondrial health.
Although regenerative medicine holds enormous promise, its development and testing can be dauntingly complex. Due to regulatory barriers and high costs, advancement can often stall. But with innovative and accessible solutions being offered by manufacturers and patient advocacy groups alike, rejuvenation could revolutionize healthcare while helping people live longer, healthier lives. Through partnerships between patients and researchers can ensure research addresses real world problems while increasing clinical acceptability.
