Science Blog
9-7-19
Josh Mitteldorf, Aging Matters

Yesterday, the TRIIM study was described in science news headlines around the world, though, through a glitch, the original research paper is not yet on the Aging Cell web site. (You saw it first here.) I refer you to the writeup in Nature’s News section for a full summary of the paper, and in this column I will add my personal framing, and what I know about the study from private connection to its authors and one of the subjects. The big news is setback of the epigenetic clock, by several methylation measures. Instead of getting a year older during the trial, nine subjects got a year younger, on average, based on the version of the Horvath methylation clock that best predicts lifespan. The study had been originally designed to regrow the thymus. (Loss of thymus function has been linked to the collapse of the immune system that occurs typically before age 70.) Imaging showed that the functional part of the thymus expanded over the course of the trial, and blood tests confirmed improved immune function. The treatment included

human growth hormone (HGH)
Metformin
Vitamin D
Zinc
DHEA
It is my belief that the age of our bodies is controlled by several biological clocks. (Greg Fahy, who conceived and conducted the TRIIM study, shares this perspective.) Candidates for clocks include

Thymic involution
Methylation profile
Timekeeper in the hypothalamus
Telomere length

Perhaps some changing homeostatic state of signal molecules and transcription factors circulating in the blood
This story is about #1 and #2. To be explicit, I’m saying that the body doesn’t wear out with age, but rather aging is a continuation of the timed growth and development program into a phase of late-life self-destruction. Just as growth and development are under epigenetic control.

Thymic involution

The thymus is a thumb-sized organ just above the sternum where our immune cells are trained to recognize self from other. It is fully developed by the time we are 10 years old, but after that it begins gradually to shrink, simultaneously losing its functional tissue and filling with useless fat. By age 25, it has already lost 30% of its mass, and by age 60 it is less than half its peak size. There is evidence that this is related to the immune decline that contributes so much to growing mortality risk with age, and that reversing that decline might lead to longer, healthier lives. A healthy immune system is important for fighting infection and for eliminating cancer cells before they become tumors. Immune aging may be related to systemic aging in other ways. (Of course, aging affects the immune system, but it also seems that the immune system may be a driving force in other aspects of aging.)

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