Researchers claim they’ve changed a mouse’s biological clock, leading them to live longer, look younger and be healthier than before – an achievement which may eventually pave the way for treatments that prevent age-related diseases as well as extend human lifespan.
According to them, the key lies within the epigenome: those chemicals and compounds which bind DNA together and control which genes are activated or inactive.
How it works
Researchers have long searched for ways to slow the aging process and extend human lifespans, with limited success. Over the last several decades, however, researchers have discovered ways to control some genes associated with cell aging using small molecules; additionally, drug trials may extend lab animal lives or possibly lower disease risks in people – though these discoveries could take decades before reaching humans.
Scientists had until now been limited in their ability to rejuvenate specific cells by genetically resetting them to their younger state, using cells known as induced pluripotent stem cells (iPSCs), which can become any cell type within the body. Researchers from California’s Belmonte Institute first developed iPSCs in 2006 and used them to make mice with genetic modifications causing premature aging but had difficulty turning back into young animals.
Last year, this lab developed the methods needed to generate iPSCs from any kind of adult cell. Since then, scientists have demonstrated that these cells can restore worn out muscles and brain cells of mice as well as reverse aging in all mice altogether. They even reported it this week!
Scientists know this research is important because rejuvenating animal cells could potentially cure any related diseases and even extend its lifespan by undoing effects of aging like weakening bones or compromised immunity systems.
To accomplish their feat, scientists made iPSCs from skin cells in a laboratory and modified them genetically so as to reactivate TERT, an anti-aging gene which certain natural substances, such as red wine resveratrol can boost. Once modified, the team inserted their genes into a harmless virus which delivered these modified cells directly into damaged retinal ganglion cells behind aged mice’ eyes where they transformed into healthy neurons that restored vision in these animals.
Results
Researchers recently created waves in medical research by rejuvenating worn-out lab mice into healthy young mice – sparking hope that this revolutionary treatment may one day be used to delay or even reverse age-related diseases in humans.
Study results after 13 years’ of investigation confirm for the first time that degradation in how DNA is organized and regulated can cause organisms to age without changes to genetic code itself. Furthermore, restoration of epigenetic integrity has shown to reverse symptoms associated with aging such as poor eyesight, decreased attention spans and skin tissues that fray over time.
Sinclair and her team used a chemical cocktail to turn adult mouse cells into pluripotent stem cells, which can grow and differentiate into any cell in the body. Following treatment with chemicals designed to manipulate epigenetics and restore youthful gene expression patterns, their cells were evaluated for signs of aging and found to be significantly younger than untreated control mice.
Mice treated for seven or 10 months appeared and behaved much like their younger counterparts, according to scientists’ examination of tissues such as kidney and brain tissue samples from these mice. When injured, these mice did not display normal aging-related metabolic molecules in their blood indicating that this treatment actually repaired DNA damage and altered how genes are expressed.
The next steps for these researchers will be to confirm their findings with other types of mice as well as human cells grown in the laboratory, before testing if long-term administration of Yamanaka factors can restore performance and function to aged cells found in kidney, brain, muscle, liver and other organs. But before that can take place, Miller says anti-ageing research requires additional funding due to two major obstacles – health politics and translating laboratory research findings into drug interventions which benefit real people.
Conclusions
Scientists have managed to reprogramm cells so they act like embryonic stem cells and reverse some signs of aging in mice over 13 years of study. Their work revealed that degradation in how DNA is organized and regulated — known as epigenetics — causes signs of aging; by restoring integrity of epigenetics they could reverse some signs. Their work, published online Jan 12 in Cell, may one day help humans heal faster after injuries while living longer lives.
Researchers employed “smart DNA” technology to alter the epigenetic pattern of mouse cells. To do this, scientists created temporary but fast-healing “cuts” in their DNA that mimicked daily damage caused by chemicals, sunlight and other factors that contribute to aging. The cuts didn’t impact gene coding but changed folding of DNA instead, leading to mice that looked and behaved more like their younger counterparts.
To gain a greater insight into how these changes impacted animals, the scientists compared ICE mice with untreated control mice and measured their biological age based on organs and tissues such as liver cell growth, formation of new blood vessels in kidneys, muscle repair after injury as well as biomarkers associated with the start of aging.
They discovered that one key indicator of biological age was levels of nicotinamide adenine dinucleotide (NAD+). When scientists increased NAD+ levels in older mice, their biological age decreased dramatically. They also studied how other events, such as surgery (both elective and emergency), pregnancy, and severe COVID-19 infection could impact biological age; after surgery biological age increased but returned to normal four to seven days later.
Researchers administered an injection to their mice that activated their telomerase and partially reversed some of the signs of aging, including poor eyesight, shorter attention spans, damaged intestinales and spleens and reduced mobility. After one month of treatment, their mice appeared, behaved and felt younger, mirroring many characteristics found in younger mice.
Authors
Since Ponce de Leon first imagined discovering the Fountain of Youth, humans have sought ways to slow aging and extend life. Aging can often accelerate serious illnesses such as cancer, heart disease and dementia – yet scientists now realize many negative effects can be reversed at least partially through reprogramming cells so they behave like younger cells.
Researchers have long noted the correlation between epigenetic changes and yeast and mammal aging, but their implications remain ambiguous. Now, scientists at the Salk Institute for Biological Studies in La Jolla, California and other laboratories worldwide have conducted a groundbreaking research project showing how epigenetic information breakdown causes mice to age prematurely; partially resetting these changes reverses this effect and reverses signs of aging in mice.
Scientists developed a technique in their lab that enabled them to temporarily create fast-healing breaks in laboratory mice DNA, mimicking low-grade DNA damage that mammalian cells experience daily due to breathing, exposure to sunlight and cosmic rays, contact with certain chemicals etc. However, most breaks did not fall within any coding regions, thus avoiding mutations and allowing epigenetic factors such as transcription factors pause before moving closer towards damaged DNA to coordinate repair; once repairs had been made they moved back back towards their original locations once repairs had completed then returned back out.
After only three weeks of treatment, mice showed significantly fewer of the normal signs of aging. Their muscles became stronger while kidneys and skin displayed epigenetic patterns more similar to young mice’. Furthermore, animals treated were more resilient against injury as they could grow replacement cells more rapidly–an ability often lost with age.
The next step will be assessing whether this treatment can work on larger animals such as primates, which will require considerable investments of money and time as well as surmounting obstacles such as health care policies and drug laws.
