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January 28, 2016

Lifespan Machine Stretches Survival Curves, Finds Causes of Aging Aligned

  • Aging appears to be an emergent property, one that remains consistent with certain underlying dynamics whether survival time is extended or not. To probe these dynamics, scientists based at Harvard Medical School built the Lifespan Machine, a device comprising 50 off-the-shelf flatbed scanners purchased from an office supplies store. Unlikely as it sounds, this machine was used to uncover patterns in the aging process that appear to have far-reaching implications.

    Specifically, it found a surprising statistical regularity in how a variety of genetic and environmental factors affect the life span of the Caenorhabditis elegans worm, a common biological model of aging since it has a conveniently short lifespan—about two weeks—and is easy to cultivate in the laboratory.

    To study lifespan dynamics of the worms at the population level, the scientists retooled their scanners to record 16 petri dishes every hour, totaling 800 dishes and 30,000 worms. The scanners capture images at 3,200 dots per inch, which is a resolution high enough to detect movements of eight micrometers, or about 12 percent of the width of an average worm.

    The worms were subjected to interventions as diverse as temperature changes, oxidative stress, changes in diet, and genetic manipulations that altered, for example, insulin growth factor signaling. The Lifespan Machine recorded how long it took the worms to die under each condition.

    Data were aggregated and lifespan distribution curves were generated for each intervention. After the results of this work were compiled, they were presented in an article that appeared January 27 in the journal Nature, in an article entitled “The temporal scaling of Caenorhabditis elegans ageing.”

    “[We observed that diverse interventions] all alter lifespan distributions by an apparent stretching or shrinking of time,” wrote the authors. “To produce such temporal scaling, each intervention must alter to the same extent throughout adult life all physiological determinants of the risk of death. Organismic ageing in Caenorhabditis elegans therefore appears to involve aspects of physiology that respond in concert to a diverse set of interventions.”

    In one sense, the findings were not surprising: Different circumstances produced different life spans. Turning up the heat caused the worms to die quickly, and turning it up higher only increased that rate. Pictured as bell-shaped distributions, certain interventions produced a thinner, high-peaked bell while others resulted in a more drawn-out and protracted bell.

    Despite these obvious differences, the researchers found an unexpected uniformity among the curves, observing what statisticians call "temporal scaling." Stated for the rest of us, if you were to take all of the bell-shaped curves and expand or contract them along the X-axes (which in this study represented time), they would become statistically indistinguishable. Simply compressing the protracted bell would produce a high-peaked bell, or vice versa. The two bells have, in a rigorous sense, the same shape.

    The various interventions seemed to affect the duration of life in the same way across all individuals in the same population, regardless of whether chance or randomness had a short or long life in store for them. No matter which genetic process or environmental factor the researchers targeted, all molecular causes of death seemed to be affected at once and to the same extent.

    "Life span is a whole-organism property," said Walter Fontana, Ph.D., a senior author of the study "It is profoundly difficult to study it molecularly in real time. But by discovering this kind of statistical regularity about the endpoint of aging, we have learned something about the aging process that determines that endpoint."

    Most important, said Dr. Fontana, this regularity suggests that there is profound interdependence in the physiology of an organism, and changes in one physiological aspect affect all others to determine life span.

    The researchers believe that their discovery will influence how scientists study, and even define, aging—for people as well as worms. The researchers now plan to study in more detail how broad statistical regularities can emerge from the action of diverse molecular mechanisms, seeking to determine exactly how alteration of one mechanism can affect all others.

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