Variation in Early Life Stress Contributes to Differences in Lifespan in Genetically Identical Worms

Why do genetically identical nematode worms raised in the same environment exhibit a distribution in life span? Researchers here suggest that differences in oxidative stress in early life are an important contributing factor, perhaps steering metabolism in some of these simple organisms towards greater resistance to the rising oxidative stress of aging. So a form of hormetic effect, perhaps. Does this have much relevance to higher animals such as our own, however?

It would be challenging to separate out early life effects of this nature from the environmental differences across the whole of life, given the existing human epidemiological data. We might consider lines of research into childhood exposure to persistent viruses such as cytomegalovirus, which hint at an earlier burden of infection leading to a shorter and less healthy later life. Or evidence for greater exposure to solar radiation in utero, via seasonal variation, to produce differences in long-term human health and life expectancy. These are not hormetic effects, but ones in which the burden of increased damage reduces health and longevity. Perhaps hormetic effects do exist, but they would certainly be harder to find in the human data.

Oxidative stress happens when cells produce more oxidants and free radicals than they can deal with. It's part of the aging process, but can also arise from stressful conditions such as exercise and calorie restriction. Examining a type of roundworm called C. elegans, scientists found that worms that produced more oxidants during development lived longer than worms that produced fewer oxidants. Researchers have long wondered what determines variability in lifespan. One part of that is genetics: If your parents are long-lived, you have a good chance for living longer as well. Environment is another part.

That other stochastic factors might be involved becomes clear in the case of C. elegans. These short-lived organisms are a popular model system among aging researchers in part because every hermaphroditic mother produces hundreds of genetically identical offspring. However, even if kept in the same environment, the lifespan of these offspring varies to a surprising extent. "If lifespan was determined solely by genes and environment, we would expect that genetically identical worms grown on the same petri dish would all drop dead at about the same time, but this is not at all what happens. Some worms live only three days while others are still happily moving around after 20 days. The question then is, what is it, apart from genetics and environment, that is causing this big difference in lifespan?"

Researchers found one part of the answer when they discovered that during development, C. elegans worms varied substantially in the amount of reactive oxygen species they produce. Reactive oxygen species, or ROS, are oxidants that every air-breathing organism produces. ROS are closely associated with aging, but instead of having a shorter lifespan, worms that produced more ROS during development actually lived longer. When the researchers exposed the whole population of juvenile worms to external ROS during development, the average lifespan of the entire population increased. Though the researchers don't know yet what triggers the oxidative stress event during development, they were able to determine what processes enhanced the lifespan of these worms.

By separating worms that produced large amounts of ROS from those that produced little amounts of ROS, she showed that the main difference between the two groups was a histone modifier, whose activity is sensitive to oxidative stress conditions. The researchers found that the temporary production of ROS during development caused changes in the histone modifier early in the worm's life. How these changes persist throughout life and how they ultimately affect and extend lifespan is still unknown. What is known, however, is that this specific histone modifier is also sensitive to oxidative stress sensitive in mammalian cells. Additionally, early-life interventions have been shown to extend lifespans in mammalian model systems such as mice.



"Does this have much relevance to higher animals such as our own, however?"

Without teasing out which form of stress, but instead, just looking at "stress as stress", and the effect of any stress too great for hormetic effect, then I wonder if this would parallel to the ACES study in humans, where number, frequency, duration and type of adverse childhood experience(s) set the stage for earlier onset adult illnesses, such as autoimmunity, ME/CFS, PTSD, and a host of others.

"I. The Adverse Childhood Experiences (ACE) Studies
The adverse childhood experiences (ACE) studies show that trauma in childhood increases risk for autoimmune 1 and other chronic diseases, additional health problems later in life 2 and in future generations. A Kaiser-CDC study with over 17,000 participants identified this connection. Results have been reproduced in other studies with different populations 3 and a continuation of the original study with over 400,000 patients.

The key point from this body of research is that the effects of childhood trauma are not just psychological. Trauma alters brain development, function and structure; autonomic nervous system regulation; physiology, stress responses 4-6, and gene function (epigenetics) 7. The American Academy of Pediatrics has used this and other research to develop a new policy 4, assessment tools, and a trauma toolbox for primary care. For more info: WHO, CDC 8, RWJ, PBS 9, NPR 10, New York Times 11, CBS 60 minutes, and news site ACES Too High.

II. ACEs Increase Risk for Chronic Illnesses and Poor Physical Health 1,2,12
Celiac disease
Chronic Fatigue (ME/CFS)*
Coronary heart disease
Diabetes, type 1 & type 2
Fibromyalgia (FMS)*
Irritable Bowel Syndrome
Inflammatory Bowel Disease
Liver Disease
Lung Disease (Asthma, COPD)
Multiple Sclerosis
Myasthenia Gravis
Rheumatoid arthritis
Sleep Disorders
Thyroid, Grave's
Thyroid, Hashimoto's
Poor self-related health
** more listed on website"

So while the worm study is more about oxidative stress, rather than psychological stress, it could still stand that the changes made in early life to any organism, cause by any form of stress to great to immediately overcome, could change the function and epigenetic landscape, and could have the knock-on effect of shortening lifespan due to stress-induced, inefficient adaptations.

The parallel is not exact, but certainly does not rule out theory or conversation as to similarity in effect.

Posted by: Adam at December 16th, 2019 5:38 PM

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