Reverse Aging – Scientists Discover a Way to Reverse Aging in Cells
Scientists have devised an ingenious way of delaying cell and organism aging using simple chemicals that reactivate genes that control how DNA folds and packages itself without altering chromosomal sequence.
Our approach draws upon Yamanaka factors that transform adult cells into iPSCs; however, our team has tailored it so as to work in all tissues – even progeria mice!
Epigenetics
Scientists have long recognized that chemical changes to DNA occur as we age. Yet researchers have been unable to establish whether those modifications are cause or effect of our aging process. A new study proves this concept by showing epigenetic changes contribute significantly to aging; by restoring those epigenetic changes reverse many signs of aging independently from changes to DNA sequence itself.
Epigenetics is the process that determines which genes are active or inactive at any given moment, using various techniques including adding or subtracting chemical groups from segments of DNA known as histones, attached to it. These chemical groups determine how the genes are read by cells. Furthermore, physical structures like chromosomes bundle genes into tightly packed chromatin and unspool them when necessary for reading; when inactive when compacted into tightly bound chromatin they’re unavailable for copying and production of proteins until unspooled when unwound.
Just like bookmarks, histone and DNA methylation marks serve as toggle switches that enable individual genes to turn on or off – this allows nerve cells to distinguish from muscle cells; and ensures healthy children grow into happy adults.
Researchers utilized temporary, fast-healing cuts in the DNA of lab mice to simulate low-grade and ongoing DNA breaks experienced by mammalian cells each day due to breathing, sun exposure and cosmic ray exposure as well as contact with certain chemicals. They observed that their epigenetic pattern began unravelling, leading them to look and act older than their chronological age and increase biomarkers associated with aging.
Scientists administered what can only be described as an epigenetic reset on these mice by replacing their histone and DNA methylation marks with those from younger animals, which led to them regaining youthful behavior, appearance, and blood biomarkers reverting back to normal. Although the team hopes that similar results might eventually apply to humans as well, for now their focus remains on discovering ways to prevent and treat age-related diseases through research such as this one.
Mutations
Theory that somatic mutations cause aging was first advanced shortly after discovering the molecular structure of DNA in the 1950s. Yet despite significant technical advancements, scientists were only recently able to test this idea using real world data. Recently however, several studies have confirmed this theory by showing mutations accumulate throughout life across cells, tissues, organs and populations – increasing risks for cancers as well as other age-related diseases.
Mutations may result from either damage to the genome or errors during replication; however, many mutations could also be due to changes in transcription patterns affecting gene expression; such alterations could ultimately contribute to cell senescence and an aging phenotype.
Demethylation refers to the process by which mutations reduce levels of methylation in our genome – known as demethylation. Demethylation mutations have been linked with health issues like cancer, inflammation and neurodegeneration; researchers have discovered that many mutations can be reversed through epigenetic restoration.
Epigenetic information influences how DNA is organized and regulated, and is thought to drive mutation accumulation. A 13-year international study involving hundreds of laboratories has demonstrated how reversing this loss can extend mice lifespan significantly while simultaneously combatting age-related illnesses.
Scientists were able to reverse the signs of aging by reprogramming cells using synthetic genes called Yamanaka factors, which are used to erase cellular identities and reprogram cells into immature progenitor cells which then replace older ones in the body – not only increasing lifespan but also completely reversing signs of aging and improving overall health in mice. This process not only extended their lives but reversed signs of aging as well.
Scientists have also successfully used this approach to target specific proteins implicated in the aging process, such as targeting the protein known as eIF4E to slow mutation accumulation in brain and heart tissue – potentially having profound implications in treating Alzheimer’s or other neurological conditions.
Chemical Rejuvenation
Harvard Medical School researchers have recently developed an effective solution to slowing aging, by “rebooting” cells that control aging. Their team used CRISPR DNA-modification technology to boost stem cells’ rejuvenating abilities while turning back transcriptional clocks that indicate ageing – this allows the team to essentially “reboot” these cells that control ageing and turn back time. Their work was published in January. CRISPR DNA modification technology helped restore stem cells’ rejuvenating abilities as well as reverse their transcriptional clocks which indicated ageing. CRISPR DNA modification technology also helped restore rejuvenation; their work was published then too.
Scientists conducted tests with their cocktail of chemicals on fibroblasts, skin-like cells that produce connective tissue. They compared the average transcriptomic age of senescent fibroblasts with quiescent cells treated with various chemical cocktails; results demonstrated that three most effective chemicals–adenylyl cyclase activators, retinoic acid and forskolin–reversed key epigenetic signatures of aging to make cells transcriptionally younger – an unprecedented demonstration of physiological rejuvenation using small molecule compounds.
Researchers used genome-wide profiling to understand how these chemicals worked, by identifying which genes were activated or inhibited. Next, they utilized high-resolution imaging technology to examine chromatin structures of treated fibroblasts versus those from healthy controls. Chemists noticed that treated cells displayed more relaxed chromatin architecture compared with controls, were less likely to be “methylated,” or marked with additional methyl groups added onto certain DNA bases, and expressed genes associated with rejuvenation more readily. Additionally, they discovered this cocktail caused senescent fibroblasts to become more relaxed while simultaneously expressing genes associated with rejuvenation of rejuvenation of cell rejuvenation as well.
Scientists are now conducting trials of their system on human cells. Their goal is to link the reprogramming genes with an antibiotic known as doxycycline so that even small doses could activate them and begin the clock rewinding process, while discontinuing usage would stop it again. This approach allows scientists to study effects on specific cell types or organs – for instance Sinclair has rejuvenated eye nerves of mice in his lab!
Genetic Rejuvenation
Scientists are exploring methods of genetically rejuvenating cells by eliminating their biomarkers of aging. One theory holds that epigenetic markers accumulate as cells age and that by eliminating these markers we can restore embryonic state for each cell. But recent research calls this traditional approach into question.
Professor Anne Brunet from Stanford University in the US conducted research published in Nature Aging which showed it is possible to rejuvenate cells genetically by restoring earlier gene expression patterns. Furthermore, this research demonstrated how old cells still contain information necessary for biological age reset in accordance with Information Theory of Aging.
Researchers successfully used Yamanaka factors to induce genetic rejuvenation of senescent cells using an approach known as inducing pluripotency or pluripotency by inducing mature cells into iPSCs and then differentiate into neurons or muscle tissue cells. They then compared these rejuvenated cells against healthy control cells not exposed to Yamanaka factors and discovered that rejuvenated ones displayed less cell damage as well as having more youthful transcriptome profiles than controls, providing proof that reverse aging at genetic level could potentially lead to new therapies against age-related illnesses such as Alzheimer’s or dementia.
Furthermore, this study indicates that biological age reversal can be achieved in vivo without uncontrolled cell growth – an essential requirement since human cells are much more resistant to genetic reprogramming techniques used in mice. This will pave the way towards rejuvenation therapies by enabling scientists to target senescent cells specifically.
OSK-mediated epigenetic reprogramming of senescent cells has been demonstrated to be feasible and can significantly decrease biological and chronological ages in mouse cells. More specifically, rejuvenation cocktail reduced multiple functions related to mitochondrial function, lysosomal function, apoptosis and growth signaling dysfunction; its rejuvenative effects were independent of c-Myc – an oncogene known to promote cancer development – for maximum effect. Additional research must be performed in order to ascertain which factors are involved.
