If aging is caused by damage, then reversal of aging – rejuvenation – can be achieved by repairing that damage. This would involve creating targeted therapies and new forms of medical biotechnology that are somewhat more sophisticated than the mainstream drug-based medicine of today. Fortunately, it is the case that for every form of damage described above there is at least one known method of repair: these repair therapies can be described today in great detail, and all that stands between us and rejuvenation is the work needed to validate and develop these new medical technologies.
The simplest and most widely agreed upon definition of aging is also the least helpful: aging is a rise in the risk of death due to intrinsic causes, meaning the failure of one or more organs or systems vital to life. A person is more aged if his or her risk of death has grown over time.
For a better explanation than this we have to ask why and how aging happens. Broadly speaking there are two schools of thought on this matter. The first, dominant school argues that aging is caused by damage, forms of wear and tear to cells and tissues, and that damage leads to characteristic changes and failures in our biology. The second, lesser school argues that aging is an evolved program of characteristic changes and failures in our biology that in turn cause damage and eventual death.
It is a mark of how complex aging is under the hood that the research community can accurately measure all sorts of damage, changes, and failures that accompany aging, but still have room to argue over whether damage causes change or change causes damage.
Regular exercise and the practice of calorie restriction with optimal nutrition are both shown to extend life in laboratory animals, but only calorie restriction reliably extends maximum life span in addition to raising the average. Both exercise and calorie restriction are associated with a longer life expectancy in humans, and improve short-term measures of health in humans in the same way as in laboratory animals. On the other side of the scale, becoming fat and sedentary are shown to shorten life expectancy and make health worse in laboratory animals, and are associated with that same outcome in humans. The amount and quality of evidence for these points are the gold standard against which other claims about health practices should be measured.
No presently available technique or medical technology has been shown to do anywhere near as well as exercise and calorie restriction for a basically healthy individual: any responsible physician will tell you this. So don’t go hunting for silver bullets that don’t exist – there are always people out there willing to sell you a lie. It’s the sad truth that you can’t exercise your way to a 100% chance of living to 100: a majority of even the fittest people with the best diets die of old age and its complications before reaching 90 in the environment of today’s medical technology.
Medical technology is key. Progress in medical technology is the greatest determinant of how long you will live and how good your health will be when you are older. Thus the more you can do to speed development towards therapies capable of human rejuvenation the longer you will likely live, and this is something that we can all help with: learn which research should be supported, make donations, and persuade your friends. All of that exercise and calorie restriction is just there to raise the odds of living to see the day on which aging can be reversed. Without future advances in medicine, you’ll age and die on roughly the same schedule as your grandparents and great-grandparents regardless of how well you look after your health.
The mainstream position in the research community is that aging is caused by an accumulation of various forms of unrepaired cellular and tissue damage. This damage then spirals out to produce evolved responses that try to compensate for damage, malfunctions in biological systems that in turn cause further harm, and so on. A few initial fundamental forms of damage spread out into many varied changes and secondary types of damage. There is considerable debate over which of these forms of damage are more important than others, and how exactly they relate to specific age-related medical conditions, but the types of damage that cause aging are fairly settled. These various fundamental forms of damage were discovered over the past century, with the most recent verified in the late 1980s, and are as follows:
1) Some tissues steadily lose cells that are not replenished and thus progressively fail in their functions with advancing age, such as the heart and areas of the brain.
2) Mutations and other haphazard alterations to our nuclear DNA occur throughout life, raising the risk of suffering just the right combination of mutations somewhere in the body that creates a cancerous cell, one that replicates uncontrollably to form tumors.
3) Our mitochondrial DNA lies outside the cell nucleus and thus accumulates damage more readily than nuclear DNA. This impairs its critical functions and leads to the creation of a small but significant population of dysfunctional cells scattered throughout the body, which cause harmful disruption to tissues and processes.
4) Some of the proteins outside our cells, such as those vital to artery walls and skin elasticity, are created early in our life and never recycled or recycled very slowly. These long-lived proteins are susceptible to chemical reactions called cross-links that glue them together or otherwise degrade their effectiveness.
5) Senescent cells are those that have suffered damage or reached the evolved limits on cell division and shut down. They should be destroyed by the immune system or by their own self-destruction programs, but over the years they nonetheless accumulate where they are not wanted, such as in the joints. Senescent cells degrade the surrounding tissue integrity and also release harmful signals that raise the odds of nearby cells becoming senescent.
6) As we age, a small handful of different proteins misfold and accumulate outside cells in clumps and fibrils known as amyloid. These are associated with many age-related conditions, such as Alzheimer’s disease, but it is not yet fully understood how they cause harm.
7) A few forms of hardy waste product build up within long-lived cells, such as those of the nervous system, impairing cellular housekeeping functions and ultimately preventing a cell from doing its job or causing it to malfunction.
Today we stand at least 20 years from the first comprehensive suite of effective therapies to either slow aging or reverse aging, even in the best of plausible scenarios – although some parts of that suite will likely emerge sooner, such as senescent cell clearance. Many of us will be old by that time: methods of slowing aging that work by reducing the pace at which damage accumulates will do very little for someone who is already aged and very damaged. A therapy that can even partially reverse aging by repairing the damage that causes degeneration will be far more beneficial to old people. Further, a therapy that repairs damage can be used over and again as damage reoccurs with the passage of time, and will provide a benefit each time it is used. Drugs that slow aging would have to be taken on an ongoing basis, producing only a small short-lasting benefit with each dose, and the end result is still that an individual will age to death. In comparison, a set of sufficiently effective repair therapies could be undertaken once every few years to indefinitely hold off the progression of aging.
The differences in utility are very clear. So if billions of dollars and decades of time are to be spent on developing either a way to slow aging or a way to reverse aging, why not work on the obviously better solution rather than the obviously worse solution, given that the costs are in the same ballpark? The real threat to our future that I see today is that the bulk of funding and present work on human longevity is focused on drug discovery to slow aging – research that will likely result in little to no benefit for anyone entering middle age today. If you and I want to live longer, healthier lives, then work on rejuvenation must instead become the priority.
