Aubrey de Grey hopes to simplify the repair of age-related damage by replacing some genetic interventions with drugs
Aubrey de Grey hopes to simplify the repair of age-related damage by replacing some genetic interventions with drugs
Speaking on Futureproof Report on November 6, aging researcher Aubrey de Grey compared the original plans for his SENS program to repair age-related damage with alternative approaches. The program’s goals remain the same, while the methods used to repair the damage may change.
SENS centers on repairing several partly independent types of damage. The body loses cells it needs, accumulates harmful substances, and undergoes changes in tissue structure. The seven SENS categories group damage by how it can be repaired: lost cells can be replaced, and waste can be broken down or removed. Once researchers have developed one method within a category, they can apply what they have learned to subsequent problems.
For cancer, de Grey sought a shared vulnerability: tumor cells need to maintain their telomeres, the protective regions at the ends of chromosomes that shorten as cells divide. Most tumors use the enzyme telomerase for this purpose. De Grey originally proposed deleting the genes responsible for telomere maintenance throughout the body, because tumor cells are difficult to distinguish from healthy cells. Healthy stem cells would also lose their ability to replenish tissues over the long term, so they would need to be replaced regularly.
De Grey now favors a drug under development that uses tumor cells’ telomerase to disrupt the protection of their telomeres. He calls this “an approach I could not have imagined twenty years ago.”
Mitochondria supply cells with energy and have their own DNA; mutations in that DNA can impair their function. De Grey’s longstanding plan is to place modified copies of mitochondrial genes in the chromosomes of the cell nucleus. The cell would use these copies to produce the required proteins and transport them into mitochondria, compensating for the effects of mutations. This plan builds on the cell’s existing machinery: many mitochondrial proteins are already produced from genes in the nucleus.
This requires introducing genes into the appropriate cells and establishing protein production and transport. De Grey sees another possibility in compounds that would help cells selectively remove mitochondria carrying mutations. This selection could increase the proportion of functioning mitochondria and preserve the cell’s energy supply.
De Grey sees partial reprogramming, an attempt to restore cells to a youthful state, as a way to reduce the need for cell transplantation. Some tissues contain cells that replenish them with new cells; this capacity declines with age. In his view, reprogramming could restore these cells’ ability to renew tissue. The protein scaffold surrounding cells also needs repair: it loses elasticity with age, making arteries, for example, less able to stretch. In de Grey’s program, repairing cells and repairing this scaffold require different interventions.
According to de Grey, some approaches to repair have already reached clinical trials, while others lag behind. This is why he chooses to work on the most difficult problems, which other researchers pass over in pursuit of quick results:
“We really need the most difficult areas to catch up with the rest.”
For comprehensive repair, he proposes combining several interventions in the same organism and testing how treatments targeting different types of damage work together.