Plugging the leaks of time

To fend off the rising cost of aging, societies need to lend greater support to geroscience’s struggle against age-related diseases

David Stipp

You might call it Murphy’s law of aging: anything that can go wrong inside you will do so if you live long enough. Yet no one experiences the full force of the law, of course, since one malady is often enough to lead to the system’s breakdown. Still, the law’s effects are increasingly familiar as ever more of us reach the biodegrading time of life. In fact, non-communicable diseases now pose a greater health burden, in terms of healthy life years lost, than communicable diseases in most countries outside of Africa.

Unfortunately, the conventional strategy in medicine, treating one disease at a time, isn’t meeting this challenge very well. One reason is that the ills of aging tend to be intractable and progressive, and by the time symptoms appear, they have often caused irreversible damage. Treatments frequently yield little gain despite racking up large medical bills. And even if one ailment can be held at bay, Murphy’s law guarantees that it won’t be long before others strike.

Worse, diseases such as macular degeneration, heart failure, strokes, arthritis and Alzheimer’s disease often leave their victims in a costly, disabled state long before they die. As a New England Journal of Medicine article on global health trends put it, “What ails most [elderly] persons is not necessarily what kills them.” Disability caused by non-communicable diseases now accounts for more than 40% of lost healthy years in the US, Europe and other parts of the developed world, according to the World Health Organization. This burden is increasing rapidly. By, 21% of the world’s population, about 2 billion people, will be 60 or older, more than triple the number in, according to the UN report World Population Ageing: . Today, the oldest nation, Japan, has a median age of 46; by mid-century, half of the people in a number of countries, including Spain, Italy, South Korea and Japan, are expected to be over 50. Meanwhile, older populations in less developed regions will have quadrupled. In China, an estimated 437 million people will be 60 or older.

ONE DISEASE AT A TIME DOES NOT WORK

Ominously, life expectancy gains in the US are already adding more years of disabling disease than healthy years to people’s lives, says Dana Goldman, a University of Southern California health economist. That’s not surprising in light of the study he coauthored in : Substantial Health and Economic Returns from Delayed Aging May Warrant a New Focus for Medical Research. The study showed that the one-disease-at-a-time strategy is likely to face diminishing returns – that is, smaller gains in longevity – even if in coming years it greatly reduces the incidence of the two leading causes of death in the developed world, heart disease and cancer. Indeed, the strategy increasingly resembles the little Dutch boy of popular legend: instead of saving the day by plugging a dike leak with his finger, he’s overwhelmed as one leak after another springs out. That’s Murphy’s law at work.

Yet it doesn’t have to be this way. Broad-acting preventive medicines could dramatically increase the period of life spent in good health – our health span. This ray of hope reflects progress in the science of aging, or geroscience. We now possess reams of data about how healthy lifestyles can lower risks of age-related diseases. Geroscientists have also discovered that altering certain genes can significantly slow time’s toll in animals to enhance longevity and health in later life.

Interventions that slow the rate of aging are now a realistic prospect. They would represent a “superefficient” way to attack the diseases of aging, says Goldman, because they would delay all of the diseases at once to extend the period of healthy life. His study showed that preventive interventions that only modestly delay aging could achieve much greater reductions in disability and per capita medical costs than the reactive approach. For example, according to research by Goldman, a drug that increased life expectancy at age 51 by only 2.2 years could, by, boost the number of healthy, non-disabled older Americans by more than 11 million.

To be sure, anti-aging interventions would likely increase the number of elderly people eligible for government entitlement programs, increasing the programs’ total costs. But Goldman’s study showed these costs could be readily offset by slightly raising eligibility ages for the programs to reflect the fact that older people would be healthier and living longer.

HOW TO DELAY AGING

Laboratory findings that suggest aging can be slowed date to, when scientists discovered that putting rats on very-low-calorie diets extends their lifespans by a third or more. Later studies showed that such calorie restriction, or CR, can delay aging in many species. Importantly, it also makes animals healthier in their extended later years.

For decades, CR remained little more than a lab curiosity. Its dietary regimen was demanding and there was no definite proof it worked in humans; its mechanism of action was too obscure to suggest drugs that would mimic its benefits. This situation began to change in the, however, when scientists discovered gene mutations in worms, flies and mice that extend healthy lifespan much as CR does. Analyzing what these mutations do within cells has suggested that there’s a latent, anti-aging capacity in the body engendered by networks of interacting genes. These networks can be switched on by CR and by mutations in specific genes, most notably those that govern growth early in life. Probing the networks’ molecular constituents has suggested that certain drugs might tap them to slow aging.

In, the U.S. National Institute on Aging launched a program to test such drugs’ effects on lifespan in mice. Six years later, it yielded an unprecedented success: rapamycin, a medicine used to prevent rejection of transplanted organs, robustly extended life expectancy in elderly mice by about a third. Subsequent studies have shown that the drug also reduces cancer, neurodegeneration and other ills while improving liver, heart, kidney and muscle function in mice. Rapamycin’s side effects, such as increased blood sugar, may rule it out as a possible anti-aging drug. But other candidates include acarbose, a drug for lowering blood sugar in diabetics, and another diabetes drug, Metformin, which mimics key effects of CR while increasing both healthspan and lifespan in mice.

Rigorously validated anti-aging drugs would still take many years to develop. Among other hurdles, scientists must find “biomarkers” to measure the rate of aging so that candidate drugs can be tested in relatively short clinical trials. Still, “it’s the beginning of the end of the beginning,” in humanity’s long quest to delay aging, says Richard A. Miller, professor of pathology at the University of Michigan. And while the modestly slowed aging that geroscientists now feel is achievable wouldn’t repeal Murphy’s law of aging, it would profoundly reduce its penalties.

Plugging the leaks of time

To fend off the rising cost of aging, societies need to lend greater support to geroscience’s struggle against age-related diseases

David Stipp

Plugging the leaks of time

To fend off the rising cost of aging, societies need to lend greater support to geroscience’s struggle against age-related diseases

David Stipp

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