The Goal of Geroscience is Life Extension

It is only comparatively recently that the research community has become supportive of efforts to treat aging as a medical condition, with researchers able to publish and speak in public on the topic without risking their careers. Even so, few researchers in this more receptive environment have been willing to be clear that the goal of treating aging is to greatly extend healthy life span, not just improve health within the life span we presently enjoy. We can hope that this too will change, and extending the healthy human life span will also come to be a topic of clear public discussion by the broader scientific community.

One cannot have large increases in life span without improved health: the two are tightly linked. Aging is nothing more than accumulated cell and tissue damage, and the dysfunction caused by that damage. A damaged machine functions poorly, and it is very hard to keep a damaged machine from complete failure by any means other than repairing the damage. To treat aging, we must repair the molecular damage that causes aging. Effective repair therapies will both improve health and extend life.

The goal of geroscience is extension of lifespan by extending healthspan. Standard medical interventions can prolong lifespan without extending healthspan (e.g., using a ventilator in comatose patient) but anti-aging interventions increase lifespan by slowing aging and thus delaying age-related diseases (extending healthspan). Healthspan is a period of life without age-related diseases. However, in comparison with lifespan, healthspan is difficult to measure, especially in animals. So why has healthspan become so popular in animal studies?

The reason is that only a few drugs were shown to extend lifespan in mammals. Other drugs seemingly increase healthspan but do not extend lifespan. This is considered an acceptable and even desirable effect. But it is not. Increased healthspan must automatically increase lifespan, if healthspan represents good health. Animals, including humans, do not die from good health, they die from age-related diseases. If diseases are delayed, an animal will live longer.

Consider a scenario in which lifespan is not increased, while healthspan is increased. To keep lifespan constant, while increasing healthspan, diseases must be compressed: start later but kill faster. For example, in this scenario, cancer kills an organism in a matter of minutes, instead of months. This is impossible. So how is it possible that some senolytics, NAD boosters, and resveratrol, increase healthspan without lifespan? The simplest explanation is that they do not increase healthspan at all, because such studies use irrelevant or ambiguous markers of health. Ambiguous parameters can be associated with either good or bad health, depending on the underlying cause. For example, similar changes in insulin signaling are associated with either slow or fast aging, depending on the mTOR activity.

Even if a drug does increase lifespan in mice and other mammals, gerontologists are still skeptical that it will work in humans. Consider an example. Calorie restriction (CR) extends lifespan in mice, rats and even monkeys. CR must extend lifespan in humans because it delays all age-related diseases in humans. Still it is debated whether it would extend life in humans. Some gerontologists think that it will not. Imagine, if CR would not increase lifespan in any mammal including mice. Would we then think that it may mysteriously extend life in humans? No. But then why are drugs that do not extend life in mice still being considered for the potential to extend life in humans? Although hundreds of recent reviews proclaim a wide arsenal of "emerging" drugs that "promise" to extend healthspan and lifespan, these drugs either do not extend lifespan in mice, or data is not sufficient.

Link: https://doi.org/10.18632/oncotarget.27882

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