March 8, 2022 / Bio Valley BIOON / --- Age may be just a number, but that number often brings unwanted side effects, from osteoporosis and muscle weakness to cardiovascular disease and cancer risk increase
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Now, in a new study, researchers from the Salk Institute for Biological Studies and Genentech demonstrate that they can safely and effectively reverse the growth of middle-aged and older mice by partially resetting their cells to a younger state.
aging process
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The results of the study were published online in the journal Nature Aging on March 7, 2022, with the title "In partial vivo reprogramming alters age-associated molecular changes during physiological aging in mice"
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"We are delighted that we can use this approach to slow aging in normal animals throughout the lifespan," said co-corresponding author Professor Juan Carlos Izpisua Belmonte of the Gene Expression Laboratory at the Salk Institute for Biological Studies
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It is both safe and effective on the body
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In addition to addressing age-related diseases, this approach may provide the biomedical community with a new tool to restore tissue by improving cellular function and elasticity in different disease conditions, such as neurodegenerative diseases and body health
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As organisms age, it's not just their physical appearance and health that changes; every cell in their bodies carries a molecular clock that records the passage of time
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Cells isolated from older or older animals have different chemical patterns on their DNA, called epigenetic marks, compared to younger or younger animals
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Scientists know that adding a mixture of four reprogramming molecules -- Oct4, Sox2, KLF4 and cMyc (also known as the "Yamaka factor") -- in adult cells resets these epigenetic marks to its original mode
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This approach allows one to dial back the developmental clock of adult cells into induced pluripotent stem cells (ips)
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Expression of reprogramming factors in tissues
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Image via Nature Aging, 2022, doi:10.
1038/s43587-022-00183-2
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In 2016, Izpisua Belmonte's lab first reported that they could use Yamanaka factor to fight the signs of aging and increase the lifespan of mice with progeria
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Recently, the team found that Yamanaka factor accelerates muscle regeneration even in young mice
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Following these initial observations, other scientists have used the same approach to improve the function of other tissues such as the heart, brain and optic nerve
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In the new study, Izpisua Belmonte and colleagues tested an improved version of this cellular regeneration method during aging in healthy animals
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A group of mice received regular doses of Yamanaka factor when they were 15 to 22 months old (roughly equivalent to 50 to 70 years in humans)
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Another group of mice received regular doses of Yamanaka factor from 12 to 22 months of age (roughly equivalent to 35 to 70 years in humans)
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A third group of mice received regular doses of Yamanaka factor for just one month at 25 months of age (roughly the equivalent of 80 years in humans)
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"What we really wanted to make sure was that it was safe to use this method over a longer time span," said Pradeep Reddy, co-first author of the paper and a Salk Research Fellow
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, behavior or weight
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Mice that received Yamanaka factor showed no changes in blood cells or changes in the nervous system compared with control mice
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In addition, the authors found no cancer in any group of animals
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When the authors looked at the normal signs of aging in the Yamanaka factor-treated mice, they found that they resembled young mice in many ways
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Mice treated with Yamanaka factor more closely resembled younger mice in epigenetic patterns in kidney and skin
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When injured, the skin cells of mice treated with Yamanaka factor were more capable of proliferating and less likely to form permanent scars -- older mice generally showed less skin cell proliferation and more of scars
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In addition, the metabolic molecules in the blood of the mice treated with Yamanaka factor did not show normal age-related changes
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The authors observed this rejuvenation in mice treated with Yamanaka factor for 7 or 10 months, but not in mice treated with Yamanaka factor for only one month
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What's more, when the Yamanaka factor-treated mice were analyzed halfway through the treatment, the effects were not as pronounced
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This suggests that rather than simply delaying aging, this treatment actively reverses it—although more research is needed to distinguish the two conditions
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The authors are now planning future studies to analyze how specific molecules and genes are altered by long-term processing of Yamanaka factors
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They are also developing new ways to deliver Yamanaka factor
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"Ultimately, we want to restore elasticity and function to old cells, making them more resistant to stress, injury and disease," Reddy said.
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This study shows that, at least in mice, there is a path to that goal
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" (Bioon.
com)
References:
Kristen C.
Browder et al.
In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice.
Nature Aging, 2022, doi:10.
1038/s43587-022-00183-2.
