Scientists have demonstrated that aging is malleable – laboratory animals can live longer by switching genes on and off; however, resetting an epigenetic pattern which determines which genes are expressed is more difficult.
Sinclair and her team have developed six chemical cocktails to revive mouse cells quickly and without harm to cellular identity, rejuvenating them within days without compromising cellular identity. The chemicals increase activity of an anti-ageing protein which has decreased significantly with age.
Epigenetics
Researchers have long suspected environmental factors could alter gene activity, yet could never pinpoint what caused them. Epigenetics could provide the answer: DNA sequences make proteins that, when altered in any way, cause disease; epigenetic changes occur when changes in how cells read those DNA sequences – these changes do not alter DNA but instead can make genes “on” become “off”, with devastating health impacts ranging from diet and exercise habits affecting genetic expressions to epigenetic influences on your health from food intake and exercise regiment.
An epigenetic mark prevents genes from turning themselves on and can last years or even for life. Some epigenetic marks are harmful – like those which prevent your body from healing itself after an auto accident or prevent cancerous cells from growing – while others can help you respond better to stress or maintain immune system health.
Epigenetic marks are created by molecules called methyl groups, which attach to your genes and alter how they’re read. Methyl groups act like erasers by turning off or slowing down their functionality – researchers are still learning how the environment impacts these methylation patterns and whether or not they can be reversed.
Studies have confirmed that epigenetic effects can be heritable, meaning they are passed from parent to offspring. One well-known example is the Agouti gene which controls hair color. Mice with its variant known as Avy have faulty controls for this gene and produce yellow fur or dark agouti coats in pups – further suggesting they exhibit more irregular genetic expression than expected. These Avy mice also tend to be obese and suffer from other health issues suggesting their genetic code might express itself more inconsistently than normal.
Sinclair’s team has pioneered an effective method for altering epigenetic states using four chemicals known as Yamanaka factors. Similar to enzymes that methylate DNA, they make changes faster and more precisely. In one experiment they applied this technique on retinal ganglion cells from mice eyes in order to restore them back into embryonic or pluripotent stem cell status – and subsequent mice regained sight as a result! They have since used it on brain, muscle, and kidney cells with similarly promising results
Stem cells
Stem cells that give rise to specialized cells in blood, bone, muscle and other tissues possess unique qualities. They’re capable of replicating themselves ad infinitum; yet have limited lifespans that will eventually cause them to stop producing and die off or enter a suspended state known as senescence; contributing to signs and symptoms associated with aging.
Scientists study stem cells to gain an insight into how specialized cells form, identify the sources of disease such as cancer and develop models of illness in the laboratory for testing new medicines.
Researchers are exploring ways to extend the lives of mice by reprogramming their cells back to more youthful states and hope this method can also work on humans. Scientists found that activating telomerase, which keeps chromosomes from shortening too rapidly leading to cell degradation, helped reverse aging on mice. Scientists then administered injections with chemicals activating this gene and revitalizing aging cells with rejuvenating treatments, leading to healthier intestinal, spleen, heart and brain organs resulting in longer, healthier lives
Scientists used an experimental compound known as ICE to reactivate telomerase. This compound works by creating temporary cuts in DNA that heal quickly – mimicking daily cell damage from chemicals, sunlight and environmental stressors like pollution and radiation. By making cuts like these in DNA, the ICE compound was able to stimulate telomerase activity and restore healthy chromosome length in mice that showed diminished sense of smell, smaller brain size, and infertility symptoms reduced significantly.
Scientists believe reprogramming cells into more youthful states may provide us with greater insight into disease development, while simultaneously developing methods to directly manipulate genes related to aging in order to extend lifespan and health. Their discoveries could pave the way towards anti-ageing treatments that could prevent or treat conditions like Alzheimer’s, Parkinson’s and diabetes; their work was published in Nature journal.
TERT
A new treatment to reverse aging on mice involves increasing the levels of telomerase reverse transcriptase (TERT), a protein that typically decreases with age. TERT helps protect chromosome ends and maintain the protective caps protecting their ends – when these caps wear away cells can no longer divide as frequently, leading to build-ups of cell debris called telomeres that eventually break down and lead to cellular senescence.
Researchers engineered mice with gene switches that caused their telomeres to wear down prematurely so they could study the impact of activating telomerase on these animals. Reactivating telomerase significantly delayed symptoms associated with aging while significantly improving health span and longevity – not to mention an increase in number of surviving cells across all tested tissues.
Reactivating telomerase was found to significantly boost cell growth and neurogenesis, reduce inflammation, improve memory, coordination, grip strength and memory tests in mice as well as slow the progression of brain tumors in the hippocampus and improve performance on memory tests.
Researchers administered AAV viruses carrying mTERT genes to mice, which allowed it to pass quickly into cells throughout their bodies and cause significant increases in TERT levels as well as an increase in telomere length across numerous tissues. At the same time, this increase coincided with decreased levels of p16, an anti-aging protein linked to cell senescence.
Harvard scientists state in their proof-of-concept study that reactivating telomerase can rejuvenate cells, but it remains uncertain if such actions would extend human lifespans. Adult humans turn off their telomerase production when they reach adulthood; it remains to be determined if activating it again would prevent cancer or simply hasten the process.
ICE
Researchers from the Salk Institute have developed an effective technique for “reversing” aging in mice using gene therapy. After making temporary cuts in their DNA, they then administered an ICE gene therapy treatment to reboot epigenetics – effectively undoing genetic “software glitches” responsible for aging – and resetting organs and tissues back to a youthful state – proving invaluable research data that may one day help scientists create strategies to extend human lifespans as well.
Researchers used the ICE gene to reprogram cells in the body so they behave like stem cells – cells with the capacity to differentiate into other types of cells and grow and divide over time – known as induced pluripotent stem (iPS) cells, and these iPS cells may then form new tissues and organs to reverse signs of aging and disease. Their next goal will be assessing if similar rejuvenation processes could help treat other diseases like heart disease or diabetes.
Scientists have long held the view that mutations to DNA were the main contributor to aging, but recent research conducted at Cell University shows otherwise. One key contributor could be changes to how genes turn on and off. The report was released recently as well.
Scientists wanted to test whether using the ICE gene would reverse aging by creating mice that experienced multiple DNA breaks. When this happens, epigenetic factors are supposed to repair them and return the genes to their original locations – however in these modified mice these factors kept becoming “distracted”, failing to return back where they should. As a result, epigenomes became disorganized.
Scientists manipulated this condition by disrupting gene expression patterns, mimicking how mammals age over time. Scientists then gave mutant mice the ICE gene and administered a drug that suppressed certain proteins; this not only caused their iPS cells to appear older but also reversed certain biomarkers of aging.
After reviewing their experiments, researchers concluded they had discovered a chemical cocktail which rejuvenates cells without altering their identity – OSK cocktail to be exact – which rejuvenates both biological and chronological age significantly below that of untreated mice. OSK significantly enhanced gene function related to senescence such as mitochondrial metabolism, lysosomal function and apoptosis which had become severely impaired over time.
