Is the secret to reversing aging in our genes?Ruslan Dorfman, PhD, MBA
The search to reverse aging and extend lifespan has intrigued humanity ever since we developed awareness of our own mortality. New scientific data now suggests that the fountain of youth is in our genes.
Researchers at the Salk Institute (La Jolla, California), reversed aging in mice by reprogramming their genome. These genetically engineered mice had a lifespan extension of 30 percent, as well as rejuvenation of internal organs and fewer overall signs of aging. To achieve this, researchers activated extra copies of four genes, called the Yamanaka genes, using an antibiotic (doxycycline) fed to mice twice a week in their drinking water. The mice used in the experiment were designed to age prematurely (a model for Hutchinson-Gilford progeria). Normal mice also showed improvement in organ health, however, it is too early to know the effect on lifespan (the mice are still alive). Humans currently cannot benefit from this type of genetic manipulation. Too much activation of the Yamanaka genes can be deadly disastrous, causing loss of cell identity and cancer. Nevertheless, this study provides exciting evidence that aging is not a finite process.
Why do we age?
The aging process holds many mysteries, and scientists have been trying to solve why some species on earth have drastically different aging schedules or ‘clocks’. Aging is clocklike in that the accumulation of cellular changes leads to cells being degraded, resulting in loss of functionality and death. However, the clock does not run the same for all species. Some species do not age for decades, only to experience sudden death after reproduction (cicadas). Other species age steadily throughout their lifetime (lizards). Some organisms achieve incredible lifespans. The giant tortoise lives upwards of 200 years and certain spruce live for thousands. Currently, humans live an average of almost 80 years in developed countries.
Yet perhaps one of the greatest mysteries, is how the clock is set back to zero at conception, regardless of the age of reproductive cells contributed by the parents.
The science of aging
Dr. Denham Harman proposed The Free Radical Theory of Aging (FRTA) in 1954, founding the field of aging science. The theory has since undergone modifications, and many notable contributions have been made. Recently, the science of aging has gained considerable interest with discoveries that aging can be controlled by modifying different cellular pathways.
Aging, at the cellular level, falls into several overlapping genetic and biochemical pathways. A few examples: genomic instability (DNA damage), telomere shortening, loss of protein quality control (proteostasis), nutrient sensing, and changes to the epigenome. The epigenome – the set of proteins and chemical groups attached to DNA – controls which genes switch on and off. The epigenome ensures that cells specific to a part of the body express the genes appropriate for that function. For instance, the epigenome activates the genes required for a cell to work as a brain neuron and turns off the genes that would make that cell specific to the heart. As we age, the epigenome accumulates changes, with certain chemical groups being added or removed. These changes alter how genes express in cells, leading to loss of function. In a way, the epigenome functions as a clock. Resetting this clock with precision is complicated as winding back too far can be deadly.
The Yamanaka genes: resetting the clock of the aging process
Japanese researcher Shinya Yamanaka identified the four genes critical to setting the clock of a fertilized egg nearly 10-years-ago. These four genes – Oct4, Sox2, cMyc, and Klf4 – can turn the cells of the body back to the embryonic state. Embryonic cells, however, easily become uncontrollable. Early experiments resulted in the death of the animals. Eventually, the correct dose of Yamanaka gene activation was achieved in genetically engineered mice.
A similar trial-and-error genetic approach for humans remains infeasible, even with rapid advances in the genome editing technology CRISPR-Cas9. Researchers at the Salk Institute have started testing drugs as an alternative. Dr. Izpisua Belmonte, the lead researcher of this project, believes drugs “will be more translatable to human therapies and clinical applications”.
Perhaps over the next century, scientists will perfect a pharmacological approach to mitigating aging in humans. Meanwhile, remember to take care of your health, and check whether Pillcheck can help to improve your medication management.
In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming. Alejandro Ocampo, et al. Cell. 2016: Volume 167, Issue 7, p1719–1733.
The Hallmarks of Aging. Carlos López-Otín, et al. Cell. 2013: Volume 153, Issue 6, p1194–1217.