The repair of aging in the human brain will have to proceed one small step at a time. Either the rejuvenation biotechnologies of the SENS program will prove sufficient to remove every aggregate and process that stops an old brain maintaining itself like a young brain does, or there must be an even more patchwork quilt of therapies, each one fixing some form of damage. The former is a much more efficient path towards meaningful healthy life extension than the latter, but the vast majority of laboratory research and related funding goes towards progress on the harder, slower road.
So reforging the brain: if we're not thinking about picking out the fundamental forms of cellular and molecular damage that cause aging and then letting the body repair itself, then the list of repairs is a long one. There is myelin to be restored where it wears away; the matter of diminished stem cell activity and so ever fewer new neurons created to replace losses; the failure of structures like the choroid plexus that remove unwanted metabolic byproducts from cerebral fluids; the malfunctioning of the brain's complex complement of immune cells; and so on for many, many more items.
Here are a couple of research releases, each looking at one small aspect of the brain's fine structure, and giving some insight into means of repair.
The source of the myelin cells in the brain and spinal cord is cell type called the oligodendrocyte. Oligodendrocytes are, in turn, the offspring of another cell called the oligodendrocyte progenitor cell, or OPC. Myelin disorders have long been considered a potential target for cell-based therapies. Scientists have theorized that if healthy OPCs could be successfully transplanted into the diseased or injured brain, then these cells might be able to produce new oligodendrocytes capable of restoring lost myelin, thereby reversing the damage caused by these diseases.
It took [researchers] four years to establish the exact chemical signaling required to [transform human induced pluripotent stem cells, or hiPSCs, into] OPCs in sufficient quantities for transplantation and each preparation required almost six months to go from skin cell to a transplantable population of myelin-producing cells.
They found that the OPCs spread throughout the brain and began to produce myelin. They observed that hiPSC-derived cells did this even more quickly, efficiently, and effectively than cells created using tissue-derived OPCs. The animals were also free of any tumors, a dangerous potential side effect of some stem cell therapies, and survived significantly longer than untreated mice. "The new population of OPCs and oligodendrocytes was dense, abundant, and complete. In fact, the re-myelination process appeared more rapid and efficient than with other cell sources."
Cognitive decline in old age is linked to decreasing production of new neurons. [Scientists] have discovered in mice that significantly more neurons are generated in the brains of older animals if a signaling molecule called Dickkopf-1 is turned off. In tests for spatial orientation and memory, mice in advanced adult age whose Dickkopf gene had been silenced reached an equal mental performance as young animals.
Neural stem cells in the hippocampus are responsible for continuous supply of new neurons. Specific molecules in the immediate environment of these stem cells determine their fate: They may remain dormant, renew themselves, or differentiate into one of two types of specialized brain cells, astrocytes or neurons. One of these factors is the Wnt signaling molecule, which promotes the formation of young neurons. However, its molecular counterpart, called Dickkopf-1, can prevent this.
Stem cells in the hippocampus of Dickkopf knockout mice renew themselves more often and generate significantly more young neurons. The difference was particularly obvious in two-year old mice: In the knockout mice of this age, the researchers counted 80 percent more young neurons than in control animals of the same age. Moreover, the newly formed cells in the adult Dickkopf-1 mutant mice matured into potent neurons with multiple branches. In contrast, neurons in control animals of the same age were found to be more rudimentary already.