"The smaller the fatter the longer the life" - the longevity mechanism of growth hormone receptor deficiency in adipose tissue

A study of mice by researchers from the Ohio University School of Traditional Osteopathic Medicine and the Edison Institute for Biotechnology showed that stopping the activity of growth hormone (GH) in fat cells improved health and extended lifespan
.

The most well-known role of growth hormone is to regulate growth; However, its existence has both advantages and disadvantages
.
It is found in many tissues of the human body and plays an important role
in many biological functions, including aging.

The concept of the study was inspired
in part by a mouse that set a record for the longest lifespan in the lab.
This long-lived mouse had no effect of growth hormone in any cells or tissues, resulting in mice that were small and obese but lived much
longer than typical laboratory mice.
The researchers wondered whether selectively removing growth hormone receptors from fat cells, rather than completely from the body, could preserve beneficial aspects of growth hormone insensitivity while limiting more harmful effects
.

"This study expands our understanding of the role of GH and how it specifically affects different tissues, producing different physiological outcomes," said Dr.
John Kopchick, who conducted the study
in collaboration with researchers Edward List, PhD, Darlene Berryman, PhD, and researchers at Dalhousie University in Nova Scotia 。 "Although the mice gained fat in this study, they were metabolically healthy and lived longer than the control mice, which means we can apply this to our own lives and help the public understand that not all fats are bad
.
"

The findings were recently published in the journal Endocrinology and won the honor
of a special article.
The findings suggest that disrupting the growth hormone receptor (GHR) gene in fat cells can improve insulin sensitivity and extend lifespan
in aging male mice.
The mice's fat mass increased, circulating levels of insulin, C-peptide, adiponectin, and resistance hormone decreased, and weakness scores improved
as grip strength increased in old age.
The researchers found that in male mice without the effect of growth hormone, about 23 percent of the increased lifespan was due to the destruction
of growth hormone in fat cells.
In a previous report, they determined that about 19 percent of the increased lifespan was due to growth hormone effects in the muscles, while women benefited less from
growth hormone disruption.

The study was conceived when the researchers considered a series of mice developed in Kopchick's lab at Ohio University that have been used to study healthy aging for more than 25 years
.
This group of mice is called growth hormone receptor knockout (GHRKO) mice, and they have no growth hormone effect in
their bodies.
They live longer, have increased insulin sensitivity, and can protect against a variety of age-related diseases
.

"In fact, this mouse was completely insensitive to growth hormone because it lacked growth hormone receptors (GHRs), and it held the record for the longest-lived laboratory mice, which lived 5 years and a week, compared to about 2 to 2 and a half years for control mice," List said
.
"We also know that growth hormone acts on fat cells, so we wondered what would happen
if we only took the growth hormone in those cells and kept the growth hormone in all the other cells and tissues.
"

After removing the GH receptors from mouse fat cells, the researchers allowed the mice to live normal lives and analyzed whether this alteration affected their metabolism and lifespan, looking at the lifespan
of obese, cytokine/adipokines, glucose homeostasis, weakness, and aging amphoteric mice.

According to this study, the data suggest that removing the effects of growth hormone, even in a single tissue, is sufficient to produce observable health benefits, promote long-term health, reduce weakness, and increase longevity
.

"This study is important because it tells us that some of the less beneficial effects of growth hormone on health occur in adipose tissue, and that growth hormone is not an anti-aging drug; It accelerates aging
.
”

List is an associate investigator at the Edison Institute for Biotechnology (EBI), where Kopchick is principal investigator
.
Kopchick is also a Gore Ohio Distinguished Scholar and Professor of
Molecular Biology.
His research focuses on human and animal growth hormone and the molecular biological relationship
between growth hormone and growth, obesity, insulin resistance, diabetes, cancer, and aging.
HE IS ALSO THE FOUNDER OF THE DRUG SOMAVERT, A GROWTH HORMONE ANTAGONIST USED TO TREAT ACROMEGALY
.
Acromegaly is a growth disorder characterized by high levels of growth hormone that, if left untreated, can lead to swollen hands and feet, facial deformities, multi-organ disorders, and premature death
.
Berryman is associate dean of the School of Research and Innovation and professor of
biomedical sciences.
Her research focuses on obesity and assessing nutritional and hormonal factors that influence adipose (fat) tissue and influence obesity risk, as well as associated diseases
.
She studies how growth hormone levels and diets with different macronutrients affect adipose tissue distribution, metabolism, and function, as well as the progression of
obesity to excessive diabetes.
In addition to List, Berryman and Kopchick, Silvana Duran Ortiz, a postdoctoral researcher at the Edison Institute for Biotechnology, and Kevin Funk, a doctoral student at the Ohio College of Arts and Sciences, are also co-authors
of the study.