Researchers have successfully reversed aging in simple organisms and are currently testing their powers in human cells. They’re searching for molecules called transcription factors that can alter gene activity on or off.
Differences in biological age often develop well before disease symptoms manifest themselves, suggesting that reversing these can delay or even stop their appearance as we get older.
1. The Yamanaka factor
Shinya Yamanaka and Kazutoshi Takahashi stunned scientists in 2006 by showing they could turn an ordinary cell into an embryonic stem cell, capable of giving rise to all other types of cells in the body. This feat was no small accomplishment since many thought reprogramming of somatic (adult) cells into embryonic stem cells required lengthy processes like gene editing.
Scientists have since demonstrated that reprogramming is possible using just four master genes – commonly referred to as Yamanaka factors after one of their discoverers – known as Yamanaka factors. With them, researchers were able to reprogram mouse fibroblast cells back into developmental states that can then become induced pluripotent stem cells or iPSCs; from here they could then become any cell type in the body including heart cells, nerves cells, skin cells or muscles cells.
Though this discovery was extraordinary, researchers wanted to see whether genetic reprogramming could also be used to rejuvenate cells already present within living organisms. Since Yamanaka first reported his work, scientists have made considerable strides toward this goal, developing chemical cocktails which can quickly convert adult cells to iPSCs without harming cellular identity or regeneration processes and regenerate treated tissue within seven days without compromise to identity.
Reprogramming factors work by reversing changes to a cell’s epigenome – the collection of chemical markers which regulate gene activity. Such changes typically arise naturally during cell development but may contribute to premature aging by restricting normal functions within cells. Researchers have used iPSC reprogramming techniques to regenerate mouse hearts and reduce scar tissue among other uses.
Yuancheng Lu of Harvard Medical School decided to try an alternate approach to cellular reprogramming. Lu and his colleagues removed one of the Yamanaka factors known to cause cancer from a mouse body before injecting the remaining three factors directly into its cells to partially rejuvenate those cells and improve age-related neurological issues like memory deficits and glaucoma.
2. Partial reprogramming
Scientists were thrilled when iPSCs and Yamanaka factors made scientists aware that partial reprogramming (using Yamanaka factors to revert aging epigenetic changes), or partial reprogramming, enabled by using different sets of factors, could partially reverse some epigenetic aging effects in cells throughout our bodies. Reversing effects on transcription via removal of inhibitory molecules is the initial step; then additional factors can be added to turn back time by delaying epigenetic age of cell and make it appear younger.
Studies, including our own, have demonstrated the efficacy of partial reprogramming on human fibroblasts. This marks an important step toward applying this technology to patients as aging fibroblasts have impaired healing capabilities that lead to various diseases like degenerative disc disease or liver fibrosis.
In our 2023 research study, we demonstrated how partial reprogramming could rejuvenate cells by erasing epigenetic markers associated with their aging and restoring normal gene expression. Furthermore, longer-term partial reprogramming regimens could slow cellular senescence and extend lifespan; an important tool in combatting age-related diseases.
Researchers continue to work toward perfecting partial reprogramming. They are investigating different chemical cocktails and delivery methods in search of the ideal combination that will enable them to turn back time on cells in vivo and thus increase its efficacy, treating more patients and prolonging lifespans.
One key area for improvement involves understanding the conditions under which partial reprogramming works effectively. A recent study demonstrated that depletion of vitamin B12 during partial reprogramming decreases its efficiency; this finding is important because lack of vitamin B12 can lead to deficiency as well as neurodegeneration, making depletion an additional source of risk.
Partial reprogramming not only extends lifespan and reduces degeneration, but it can also boost cognitive performance. A recent study reported on how reprogramming fibroblasts from older mice to their younger states with doxycycline resulted in improved cognitive performance as evidenced by reduced amyloid-beta plaques, senescence markers and dendritic spines as well as increased synaptic strength and memory in mouse models of Alzheimer’s disease; an encouraging step forward to eventually using partial reprogramming to restore function for human patients suffering dementia.
3. Stem cells
Stem cells are master cells in our bodies, capable of both self-renewal and differentiating into more specialized cells as they age and mature. Stem cells provide the foundation upon which all other cells develop – serving as building blocks to form more mature ones later on. Stem cells also possess remarkable abilities of self-renewal – producing more stem cells as they mature to form healthy tissues where needed.
Stem cell research is one of the fastest-expanding fields of medicine, offering hope of reversing age-related diseases, improving health and well-being and perhaps even prolonging lifespans.
Although stem cells can be found throughout the body, they play an especially vital role in organs and tissues in need of replacement or repair, making them perfect candidates for regenerative medicine treatments aimed at combatting age-related conditions such as Alzheimer’s and heart disease.
Scientists have recently made groundbreaking advances in reprogramming stem cells in the laboratory into any cell type imaginable – heart, blood and muscle cells among others – replacing damaged tissue or even regeneration new tissue growth. This technique may eventually be explored for Parkinson’s disease treatment as well as diabetes management, heart failure management and osteoarthritis relief.
Stem cells have demonstrated healing and anti-inflammation benefits in animal models, as well as being used for safety testing of new medications before giving them to people.
Recent evidence in mice suggests that human stem cells can help combat age-related vascular dysfunction and neurodegeneration, protecting against neurodegeneration. Stem cells were shown to restore normal vascular structure and function by modulating microRNAs involved with remodelling processes like the cGAS-STING pathway or epigenome.
Researchers are investigating using human stem cells as an innovative therapy option for treating various illnesses, from blood cancer and bone disorders to chronic inflammation and diabetes. Stem cells extracted from fat tissue or bone marrow of patients can then be reprogrammed in a laboratory environment into specific cell types needed. Finally, IV infusion can then deliver them back into the body.
4. Plasma
Plasma is one of the four states of matter, along with solids, liquids and gases. When heated gas changes into plasma – made up of positively charged particles called ions and negatively charged electrons. Plasma exists throughout outer space such as in nebulas and stars like our Sun; not visible but making up over 98% of it’s total volume! Plasma also exists around electrodes used for medical treatments or lightning bolts – as well as being present within our everyday air!
Researchers using parabiosis surgery found that when two rodents of different ages were surgically joined together through their circulatory systems, blood from a younger one rejuvenated organs of older animals – leading them to suggest plasma transfusion as an antiaging therapy option for humans.
Some scientists, including Robert Wyss-Coray of Robert Wyss-Coray Ventures, believe exchanging plasma between people could slow biological aging and help stop disease progression. To test their theory in humans, they’re using a plasma fraction composed of young, fresh frozen plasma with albumin as carriers to test this theory in humans; albumin is known for rejuvenating cells due to being the carrier for hundreds of other proteins; thus possibly rejuvenating aged ones as well.
Plasma can easily traverse through our body’s circulatory system and reach all tissues, unlike many drugs. Clinical trials on animals have so far yielded promising results but it remains uncertain if such early results will translate to human patients.
Plasma science, the study of ionized gases and their interactions with materials, is an amazingly versatile field, offering solutions in space physics/astrophysics/material science/atomic, molecular and optical physics/biologics as well as medicine/agriculture. Horvath works at Princeton Plasma Physics Laboratory of the Department of Energy where she has helped advance technology necessary for fusion power development.
Emma, a young girl living with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), requires plasma medicines every week in order to avoid paralysis from her neck down. Each year it takes 155 plasma donations in order to provide her with enough treatment.
