Science is founded upon observing and measuring natural phenomena. This can involve anything from recording temperature or rainfall amounts, to building large-scale observatories that detect subatomic particles.
Shinya Yamanaka revolutionized cell biology when he discovered how cells could be reprogrammed back into embryonic state without altering their code or becoming cancerous, leading to him winning a Nobel Prize for this groundbreaking discovery. His lab developed methods to reprogramme cells without changing their DNA code or making them cancerous.
Reprogramming T Cells
Researchers have unlocked a way to revive T cells – white blood cells which help fight cancer and other diseases – through genetic modification. When introduced into mice, genetically modified T cells fought cancer as well as making older ones healthier and younger, making life more productive overall. According to researchers, their results represent “an initial step towards increasing healthy lifespan”.
T cells require constant reprogramming in order to perform their critical immune functions, including finding and eliminating pathogens such as viruses and bacteria, as well as sensing changes to our tissues and organs. Without enough reprogramming, old T cells stop responding to threats as effectively and eventually die; when removed from the body, young healthy T cells replace them, helping restore immunity’s full effectiveness.
However, as people age they experience an increase in senescent T cells that can lead to inflammation and age-related diseases as the immune system becomes compromised. To combat this trend, scientists aim to increase the number of reprogrammed T cells within our bodies; their experiments with mice have been successful while the next step will be finding an approach for human patients.
Scientists are exploring other strategies to postpone age-related disease, such as caloric restriction and using the drug rapamycin which blocks an important molecular pathway in cells. Unfortunately, however, these solutions only address individual disease processes without addressing its underlying causes.
Reprogramming methods have also been employed as part of research to try to reverse what scientists refer to as an “epigenetic clock,” or alter how a cell expresses its genes. To do this, researchers use DNA with instructions for reprogramming injection into cells whereby binding takes place resulting in turning on stem cell genes while silencing adult-identified genes.
Shinya Yamanaka pioneered this field of research and discovered that only four transcription factors are required to transform fully mature cells into pluripotent stem cells with all the properties of embryonic tissue. But the key for human patients will be understanding how to prevent creating tumorigenic stem cell reservoirs which could lead to cancer or other serious medical problems.
Reversing Aging in Mice
Scientists have long recognized that mice can reverse certain hallmarks of aging, including accumulation of damaged proteins and reduced ability to repair tissue damage. But how? According to scientists, they believe the key lies in the epigenome, an ensemble of proteins and compounds which coat DNA to control whether certain genes turn on or off.
Researchers discovered in the 1990s that cells of yeast modified through gene-switch were significantly more resistant to damage and regeneration faster than their unmodified counterparts. Assuming the same method would work on mammals, scientists extended lifespan by up to 25% while simultaneously finding healthier bodies with stronger muscles that developed less cancerous tumours than untreated animals.
Salk Institute researchers from La Jolla, California demonstrated that signs of aging could be eliminated in cells exposed to four Yamanaka factors for short duration without altering or killing them; their research was reported by Nature Aging magazine on March 7, 2022.
Scientists used a virus to deliver rejuvenating Yamanaka factors directly to damaged retinal ganglion cells in an aged mouse’s eye, where they not only regenerated but also sprouted new axons connecting its retina with its brain – providing evidence that whole organ rejuvenation had taken place.
Scientists analyzed the DNA of ICE mice to see how many sites had lost the methyl groups that are typical markers for old cells, and discovered that their methylation patterns resembled more closely those found in younger mice – suggesting reversing this process could be key in slowing cell aging.
Researchers have since used their technique to rejuvenate other parts of mice bodies using muscle and brain rejuvenation techniques, with Sinclair anticipating that this can one day be applied to human cells for whole-body rejuvenation. Unfortunately, however, obstacles remain which make the market for anti-ageing drugs difficult.
Reversing Aging in Humans
Scientists have long explored ways to slow and reverse some of the most damaging aspects of aging. One approach known as the “Ship of Theseus” may allow us to swap biological parts with synthetic ones so as to live longer and healthier lives; although, while such procedures might theoretically work in some instances, scientists have discovered it’s often too hard or costly for humans to implement them effectively.
For centuries, scientists believed that aging was unstoppable. Recently however, researchers began to realize that many age-related diseases could be delayed or reversed through correcting cell damage.
Researchers focused on telomere shortening as an indicator of cell division; as cells divide, their telomeres get gradually shorter until eventually they disappear altogether and leave cells too damaged to repair themselves; this damage contributes to many diseases associated with aging.
Sinclair and her team at Harvard Medical School successfully reversed human cell aging with medications designed to reverse gene expression associated with aging, as well as high-throughput cell-based assays to identify chemical cocktails which rejuvenated old cells; their study identified six chemical combinations which restored cell growth while simultaneously reversing transcriptomic aging of test samples.
Though this was an exciting development, it remains uncertain if any of these compounds will work to extend human longevity. One major difficulty lies in how biological ageing occurs years before symptoms appear for disease; therefore any treatments would need to start early on in life.
But even if these approaches can be translated into human treatments, it will likely take decades before such therapies reach clinics. Dermatologists, however, continue to make inroads into reversing the effects of aging by smoothing away fine lines and wrinkles with laser therapy or light therapy treatments.
Reversing Aging in Plants
Researchers have recently demonstrated how certain cells can be coaxed into acting like stem cells and rejuvenating new tissue to reverse signs of aging, marking an important step toward their ultimate goal: turning back time at the cellular level while rejuvenating whole bodies.
Though various human and animal studies have demonstrated the possibility of increasing lifespan for simple organisms, scientists are still learning how to reverse the natural ageing process in higher complex animals – however UC Riverside scientists may have made progress by discovering an integral link between one organelle of plants and aging processes.
Plant cells contain an organelle known as the Golgi body that’s essential for combatting stress and prolonging longevity, known to scientists for over 100 years but only recently recognized by researchers at UC Riverside as playing an essential part in the aging process.
This research team originally set out to understand how a specific protein in plant cells affected their responses to various stressors, such as infections, excess salt or lack of sunlight. By chance, they came upon evidence for Golgi bodies’ essential role in protecting against cell death and slowing aging processes.
Evidently, adding four reprogramming molecules (Oct4, Sox2, Klf4 and cMyc) to a cell can reset its molecular clock. Epigenetic markers consisting of chemicals that tag DNA change their patterns over time to reflect biological aging rather than chronological age – by resetting these epigenetic markers scientists can transform old cells into youthful and healthy new ones.
Yamanaka factors were added to mouse cells, and as a result they behaved as stem cells and produced healthy young mice. Researchers are currently applying this knowledge to other animal and human cells; should this work be successful it could allow for the creation of pills which rejuvenate and prevent age-related illnesses.
