1. Cell Loss Our liver, kidneys and other organs keep a fair number of cells in reserve; still, over time, cell loss may impair their functioning. De Grey’s fix: Engineer embryonic stem cells to create healthy new versions of every type of body cell. Introduce the stem cells into the body to rejuvenate diseased or flagging tissues. The mechanism to deliver the various cell types to all the right places has yet to be developed.
2. Cell Senescence Cells that have stopped dividing often loiter instead of dying. Judith Campisi of Lawrence Berkeley National Laboratory theorizes that these cells may induce neighbors to become cancerous. De Grey’s fix: Experiment in mice to find ways to destroy these old cells. One approach is to insert “suicide” genes that make the cells self-destruct. Another is to find ways to turn the body’s immune system against them.
3. Lysosomal Junk Waste that builds up inside cells is broken down by enzymes in cell structures called lysosomes. Over time, lysosomes can get saddled with undegraded material; diseases such as age-related macular degeneration may result. De Grey’s fix: Borrow genes from soil microbes and put them to work producing enzymes with a taste for lysosomal garbage.
4. Extracellular Junk Waste also builds up in the spaces between cells. Dead immune-system cells and cholesterol plaque that accumulate inside arteries may cause atherosclerosis; plaque that builds up around neurons may contribute to Alzheimer’s disease. De Grey’s fix: Genetically rewire the immune system to engulf the junk outside the cell and transport it inside, where lysosomes can digest it.
5. Sugar-Protein Molecular Bonds As we age, glucose and other sugar molecules bond with protein molecules, creating rigid layers of tissue and potentially causing problems such as blood-vessel hardening that can lead to high blood pressure. De Grey’s fix: Develop more compounds like ALT-711, a re-
cently discovered chemical that has been shown to break one type of glucose-protein bond.
6. Mitochondrial DNA Mutations “Free radicals”—the unstable molecules created when glucose is broken down to make energy—may alter DNA, causing potentially harmful mutations. Mitochondria are especially vulnerable to such assaults because of their role as the
cell’s power plants. De Grey’s fix: Transfer mitochondrial DNA into the cell
nucleus for safekeeping.
7. Nuclear DNA Mutations Mutations of the DNA in the cell nucleus contribute to cancer. De Grey’s fix: Extract cells from the patient. Switch off their ability to produce telomerase, the enzyme that facilitates cell division, and modify them to tolerate toxic chemotherapy. Return cells to the patient, who can now be given chemo to kill off any growing cancer cells. After periodic cell “reseedings,” the cells will lose their susceptibility to cancer.
