Longevity Medicine
Therapies halting/reversing the root causes
of age-related degeneration
Regenerative medicine helps create an environment in which missing or damaged tissue, that normally does not re-grow, can regenerate fully through cell manipulation and the use of scaffold materials that emit biochemical signals to spur someone’s stem cells into action.
Regenerative trial therapies have healed broken bones, bad burns, blindness, deafness, heart damage, nerve damage, and damage caused by ‘aging’. Aging also damages the stem cells required for regenerative therapies!
In 2008, researchers have found what may be a shortcut to the growth of replacement organs from a patient”s own stem cells.
The process takes a donor organ and chemically strips the cells from it, leaving only the scaffolding of the extracellular matrix behind. Stem cells from the organ recipient are then used to re-populate the scaffold, creating a functioning organ ready for transplant with little risk of rejection.
Researchers at Russia’s Altai State University developed a medicine that stimulates the body’s stem cell production, reinvigorates tissues and maintains them at levels which correspond with those of a biologically young organism.
Synthetic biologists focus their attention on re-engineering the human genome, for ways to cure diseases. This also involves the epi-genome and epi-genetics.
Other research showed that ‘splicing factor’ genes switch off as humans age. Scientists found a way to restart the splicing by treating old cells with molecules that restore the levels of the splicing factors. Cells are now able to grow, and their telomeres are now longer, like in young cells.
Some researchers believe we may be able to slow down—and even turn back—the clock that governs aging in our cells.
We all age chronologically with the passage of time, but what about our bodies? Is physiological aging inevitable too? A growing cadre of biologists says no, thanks to developments in the field of epigenetics, which studies the processes that determine how our genes “express” themselves in directing our cells throughout our lives.
Imagine your DNA, as a piano keyboard, then epigenetics determines how the keys play music. The primary players in this concert are molecular substances that affix to your genome and leave markers.
These markers give cells specialized functions and regulate how they function. If too many markers accumulate—too much “epigenetic noise”–the directions become muddled, and cells become dysfunctional.
Recently, researchers learned that these markers can offer a remarkably accurate measurement of your biological age. That insight led to a more startling finding that epigenetic markers not only measure aging but help cause it.
When researchers at Harvard added epigenetic accretions to the genomes of young mice, they experienced an accelerated loss of muscle and bone mass, turned gray, lost sight and became more easily confused.
The results of these experiments are helping solidify an “information theory” of aging, which says that an accumulation of epigenetic noise interferes with genetic data. The chaos eventually causes cells to become senescent and stop reproducing and influence adjacent cells to do the same. That is the experience we call aging.
The origins of this process can be found in the earliest era of microscopic life on earth. Simple organisms evolved signals to reproduce cells when conditions were favorable and to shut down and attend to any damage when conditions were poor.
We suffer from aging, as a side effect of a primeval program that regulates and repairs our cells. As such, aging is like cancer, which also evolved as a survival mechanism, allowing cells to abandon higher functionality.
Initially, we considered cancer as just a part of life. Now, we correctly call cancer a disease, and fight against it. We should regard aging in the same way, because a disease is a condition that prevents the body/mind from working normally!
Aging is thus “the mother of all diseases.” While smoking increases the risk of getting cancer several-fold, at 50 the risk of cancer increases over 100 times. At 70, it is over 500 times. Aging is a major factor in heart disease, dementia, stroke, type-2 diabetes.
Curing any of these diseases, increases the average lifespan by only a few years, because the risk of all other diseases continues to increase, thru the driving force of aging. But reduce them all, by addressing them at the cellular level, the potential for extending productive, healthy human lives is much more significant.
There is no law of biology that says we must age at the rate at which we do now. Other forms of life don’t. The bristlecone pine can survive for 5,000 years and does not appear to experience aging.
The jellyfish known as Turritopsis dohrnii is made up of cells that can reverse and become juvenile cells, and seems to be functionally immortal.
If a retina can be rejuvenated,
what else can?
Epigenetic markers of deterioration/aging can accumulate from unhealthy behaviors, like damaged DNA from sun overexposure, or poor diet, or smoking. If we can reboot the cell, we would have the potential to stem or reverse cellular aging. It would allow an older body to heal and to fight against age-related diseases more like young people do.
At the Salk Institute, researchers showed that the lifespan of mice suffering from premature aging could be extended by 30% by transiently turning on 4 genes that are known to wipe out accumulated epigenetic markers and induce “pluripotency,” the ability of a cell to develop into any other form of cell in an adult body. By partially resetting the program, the mice seem to have experienced a taste of what life is like as an immortal jellyfish.
In the Sinclair lab at Harvard, researchers administered a combination of 3 genes to blind old mice and turned the genes on for 3 weeks. The treatment rejuvenated their optic nerve cells and restored their vision. If something as complex as a retina can be rebooted to a youthful state, potentially multiple times, what else can?
Dr. Sinclair and others have started a company to develop medicines for eye diseases based on this science. However, would it be a good idea to lengthen human lives if we cannot substantially improve our living free of debilitating diseases?
The same team reported that 9 patients treated with a cocktail of 3 molecules —growth hormone, DHEA, and metformin— experienced an epigenetic age reversal, shedding 2 years off their biological ages.
Cited papers:
- Reversal of ageing- and injury-induced vision loss by Tet-dependent epigenetic reprogramming.
- In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming.
- Erosion of the Epigenetic Landscape and Loss of Cellular Identity as a Cause of Aging in Mammals.
- DNA Break-Induced Epigenetic Drift as a Cause of Mammalian Aging.
- Epigenetic changes during aging and their reprogramming potential.
