Fight Aging!

While it is still a small field in comparison to much of biotechnology and medicine, research into slowing and reversing the aging process has achieved legitimacy and growth in the past decade. This newfound capacity for progress results from a great deal of work by patient advocates, visionary researchers, and other allies to overcome public disinterest and a hostile leadership in the field of gerontology.

Sadly, most participants in the now energized research and development communities are pursuing varieties of a poor strategy, often called geroscience. They have taken the wrong realization regarding the plasticity of aging, and are working on lines of development that are unlikely to produce large effects on human life span. This work descends from the earliest and best supported modern investigations of aging interventions. It involves the search for longevity-related genes, near all of which manipulate stress response systems (such as autophagy) that can slow aging in short lived animals. Calorie restriction research is one of the major areas of work, but there are numerous others that touch on ways to make animal metabolism more optimal for longevity than is the case in the wild.

Unfortunately, we already have all the evidence we need to show that these systems of cellular maintenance - activated by stresses such as starvation, cold, heat, and toxins - have comparatively small effects on longevity in long-lived species. Calorie restriction extends life by up to 40% in mice, but it certainly doesn't add more than a few years in humans. Further, the practice of calorie restriction cannot greatly reverse the state of aging once it has occurred. It is very much a case of better than nothing, but not a road to dramatic rejuvenation or lengthening of life.

Some people see the uptake of interest in aging research and the building of a longevity industry, and feel justified in saying that an inflection point has passed. That is the case in today's open access paper, quoted below. The real inflection point still lies ahead, however, in the adoption of a truly viable strategy to produce human rejuvenation - a strategy based on damage repair that is quite different from the majority of present work on aging. This inflection point will occur when significant portions of the research community buckle down to work on repairing the molecular damage that causes aging, rather than tinkering with metabolism to slightly slow down the accumulation of that damage. This transition has yet to happen. Until it does, progress will be marginal.

From discoveries in ageing research to therapeutics for healthy ageing

The rapid increase in our understanding of the molecular mechanisms that underlie ageing has created new opportunities to intervene in the ageing process. Two notable findings have emerged from these early studies. First, the number of genes that can extend lifespan is much larger than expected, which suggests a much higher level of plasticity in the ageing process than expected. Second, genes that control ageing - which define cellular pathways such as the TOR and insulin signalling pathways - are remarkably conserved in yeast, worms, fruit flies and humans. The conservation of these pathways across wide evolutionary distances and the fact that targeting these pathways in model organisms increases both lifespan and healthspan has brought to the fore the idea of interventions in humans.

Rapidly ageing societies across the world are seeing an increasing healthcare burden attributable to both morbidity and cost of age-related diseases, such as heart disease, stroke, cancer, neurodegeneration, osteoarthritis, and macular degeneration. However, current medical care is highly segmented as well as organ- and disease-based, and ignores the fact that age and the ageing process are the strongest risk factor for each of these diseases. According to the concept of geroscience, targeting conserved ageing pathways is anticipated to protect against multiple diseases and represents a different approach to tackling the rapidly growing burden of diseases worldwide.

The concept of geroscience predicts that conserved ageing pathways are part of the pathophysiology of many age-related conditions and diseases. For example, multimorbidity is seen as the multisystem expression of an advanced stage of ageing rather than a coincidence of unrelated diseases. Targeting conserved ageing pathways should, therefore, prevent or ameliorate multiple clinical problems. This hypothesis remains to be tested in clinical trials, but is supported by several lines of evidence. A wide range of animal models of specific diseases can be affected by manipulating a single ageing mechanism (such as NAD+) or senescent cells in the laboratory. Rates of individual age-related diseases and of multimorbidity increase nonlinearly with age, and the rate of acquiring new chronic diseases may be higher in people who have an existing chronic disease.

We are now entering an exciting era for research on ageing. This era holds unprecedented promise for increasing human healthspan: preventing, delaying or - in some cases - reversing many of the pathologies of ageing based on new scientific discoveries. Whether this era promises to increase the maximum life span of humans remains an open question. What is clear is that, 30 years after the fundamental discoveries that link unique genes to ageing, a solid foundation has been built and clinical trials that directly target the ageing process are being initiated. Although considerable difficulties can be expected as we translate this research to humans, the potential rewards in terms of healthy ageing far outweigh the risks.