Leverage the Malleability of Aging


Professor Janet M. Lord gave the 15th annual Keynote Medical Research Council (MRC) Lecture on Wednesday during the SOT 58th Annual Meeting and ToxExpo. In her talk, titled “Ageing and Multimorbidity: Time for a New Approach,” we were reminded of the rise in aging populations around the world and the health care burden that this brings. At the Queen Elizabeth Hospital Birmingham, United Kingdom, in the last six months of 2017, there was no single presenting disease that could be identified as the leading cause of emergency department visits, and subsequent hospitalization, in those over the age of 50. In this hospitalized population, on average, each patient had six comorbidities, and their length of stay was more strongly related to number of comorbidities than to age itself. In order to tackle these comorbid diseases, Professor Lord suggested we tackle the process of aging itself!

Aging has been deemed malleable through several experiments, across different species. In worms, flies, mice, and primates, caloric restriction, altered IGF signaling, and exercise have been associated with an increased life span. Caloric restriction has also been shown to increase the health span of primates, who remain physiologically and physically healthier than their non-caloric-restricted age counterparts. A natural experiment in Okinawa, Japan, suggests caloric restriction can induce longevity along with an improvement in health span in humans, too. These findings have led researchers to look for targets in pathways related to caloric restriction and altered IGF signaling. A few molecules have been identified and are now in clinical trials for this ability. The diabetic drug metformin is one such molecule. It activates AMP kinase and promotes autophagy and cellular clean-up of accumulated damage. Cell senescence has been implicated as a cause of aging-related decline in health since senescent cells can produce pro-inflammatory markers and release angiogenic signals. Genetically engineered mice that delete senescent cells have shown better life span and health span. Molecules that target and kill senescent cells, senolytics, have shown potential to improve health outcomes associated with a range of age-related diseases including osteoporosis and frailty.

To understand whether physiological changes seen over time are a result of underlying aging physiology or due to lifestyle factors, the group recruited lifelong cyclists (cycling > 15 years) and studied their blood and muscle biopsies. Turns out, many of the regular hallmarks that have previously been attributed to aging don’t hold up in this population. As they age, they did not show an increase in body fat, there was no increase in insulin resistance, and no real measure of sarcopenia was seen. In the lifelong cyclists, the reduction in size of the thymus over age was much lower than age-matched noncyclists and they did not appear to be statistically different from a young population. Their cardiopulmonary function did decline, suggesting this could be attributed to the intrinsic aging process.

Professor Lord presented convincing evidence that aging is a malleable process and in understanding the drivers of most age-related diseases, we should consider changes in physiology that result from aging itself. She also provided compelling evidence that lifestyle factors play a significant role in aging and that exercising can stave off most reduction in function associated with aging.

This blog was prepared by an SOT Reporter. SOT Reporters are SOT members who volunteer to write about sessions and events they attend during the SOT Annual Meeting and ToxExpo. If you are interested in participating in the SOT Reporter program in the future, please email Giuliana Macaluso.

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