Summary: New research has revealed that aging triggers a novel stem cell that produces large cell quickly, which is what causes belly fat to frequently increase in middle age. Scientists found that aging triggers adipocyte progenitor cells ( APCs ) to evolve into committed preadipocytes, age-specific ( CP-As ), which actively generate new fat.
This fat-cell development is mediated by a indicating road called LIFR. These findings may help develop new treatments for CP-As to stop aging fat get and physiological disorders.
Important Facts:
- Aging Causes the Emergence of CP-A Cells, which produce a large number of new large tissues.
- Important Pathway identified: Middle-aged fat cells are fueled by the LIFR signaling road.
- Possible Therapy Target: Blocking CP-As may help decrease age-related stomach fat and extend healthspan.
Origin: Hope City
Our waistlines frequently increase as we get older, but this is not just a plastic issue. Belly fat drives aging and slows down digestion, increasing our risk for developing diabetes, heart problems and other serious conditions.
However, it’s unclear how time changes a six bottle into a soft stomach.
The mobile factor responsible for age-related belly fat has been identified in experimental studies by City of Hope, one of the largest and most cutting-edge research and treatment centers in the country and a leader in diabetes and other lethal illnesses. This provides fresh insights into why our midsections get wider with mid age.  ,
Published now in , Science,  , the findings suggest a tale target for potential therapies to reduce belly flab and expand our good lifespans.
People often gain body fat and muscle as they get older, even when their body fat is unchanged, according to Qiong ( Annabel ) Wang, Ph.D. One of the most important medical organizations in the world, the Metabolism Research Institute, Arthur Riggs Diabetes &, is Dr., co-author of the study and associate professor of molecular and cellular physiology at City of Hope’s.
” We discovered aging causes the appearance of a novel form of adult stem cell and enhances the body’s large production of new large cells, particularly around the stomach”.
In collaboration with Xia Yang, Ph. D., co-author of the UCLA laboratory. D., the researchers conducted a number of mouse experiments that were later validated on human cells. Wang and her colleagues focused on white adipose tissue ( WAT ), the fatty tissue responsible for age-related weight gain.
The scientists speculated that WAT expanded by producing new fat cells, which would indicate that fat cells grow bigger with age. This suggests that it has untapped potential to grow.
A group of stem cells from WAT that develop into fat cells was the subject of the researchers ‘ investigation to test their hypothesis.
The City of Hope team first transplanted APCs from young and older mice into a second group of young mice. A colossal volume of fat cells were quickly produced by the older animals ‘ APCs.
However, the stem cells did not produce many new fat cells when the team transplanted APCs from young mice into older mice. The results confirmed that older APCs are equipped to independently make new fat cells, regardless of their host’s age.
The scientists then compared APC gene activity in young and older mice using single-cell RNA sequencing. APCs woke up with a vengeance in middle-aged mice and began pumping out new fat cells, despite being barely active in young mice.
” While most adult stem cells ‘ capacity to grow wanes with age, the opposite holds true with APCs— aging unlocks these cells ‘ power to evolve and spread”, said , Adolfo Garcia-Ocana, Ph. The Ruth B., D. Robert K. Lanman holds the Chair of the City of Hope’s Department of Molecular & Cellular Endocrinology and holds the Robert K. Lanman Endowed Chair in Gene Regulation & Drug Discovery Research.
” This is the first evidence that our bellies expand with age due to the APCs ‘ high output of new fat cells”.
Age-specific ( CP-As ), a new branch of stem cell, were created from the APCs in the form of committed preadipocytes. Increasing in middle age, CP-A cells are actively producing new fat cells, which accounts for why older mice put on more weight.
A signaling pathway called leukemia inhibitory factor receptor ( LIFR ) proved critical for promoting these CP-A cells to multiply and evolve into fat cells.
We discovered that LIFR is the body’s main factor in the fat-making process. Young mice do not require this signal to become fat, but older mice do,” Wang said.
” Our research indicates that LIFR plays a crucial role in triggering CP-As to create new fat cells and expand belly fat in older mice”.
Wang and her colleagues then conducted a lab analysis of APCs from human tissue using single-cell RNA sequencing on samples from people of various ages.
Again, the team found CP-A cells that were more prevalent in the tissue of middle-aged people. Their discovery also illustrates that CP-As in humans have high capacity in creating new fat cells.
Our findings “raise the importance of preventing new fat cells from form in order to treat age-related obesity,” Wang said.
Understanding the roles of CP-As in metabolic disorders and how these cells develop as they age could provide new treatments for belly fat loss and longevity improvements.
Future research will focus on tracking CP-A cells in animal models, observing CP-A cells in humans and developing new strategies that eliminate or block the cells to prevent age-related fat gain.
Guan Wang, Ph. D., the study’s first author, is Guan Wang, Ph. D., City of Hope. and Gaoyan Li, Ph. D., from UCLA. D.
About this research on aging and weight gain news
Author: Letisia Marquez
Source: City of Hope
Contact: Letisia Marquez – City of Hope
Image: The image is credited to Neuroscience News
Original Research: Closed access.
By Qiong A.,” Active adipogenesis is fueled by distinct adipose progenitor cells that emerge with age..” Wang et al. Science
Abstract
Active adipogenesis is fueled by distinct adipose progenitor cells that emerge with age.
INTRODUCTION
Adipose tissue exhibits significant compositional and phenotypic plasticity and plays a crucial role in controlling various hormonal and metabolic processes. From middle age to early aging, adults often experience a notable increase in visceral adipose tissue mass.
Visceral adiposity is thought to be a significant risk factor for various metabolic conditions. Adipose tissue accumulation occurs through two primary mechanisms: adipocyte hypertrophy and adipogenesis. However, the mechanisms by which early aging contributes to adipose tissue accumulation remain poorly understood.
RATIONALE
Adipogenesis is the process by which adipose progenitor cells ( APCs ) multiply and differentiate to become new adipocytes. In an in vitro, two-dimensional ( 2D ) culture setting, earlier reports suggested that older humans or rodents exhibit a lower capacity for adipogenesis.
In this work, we used in vivo lineage tracing mouse models, 3D profiling of APC transplants to monitor , adipogenesis of APCs up to middle age, and single-cell RNA sequencing to identify distinct types of APCs generated during this life stage.
These age-specific APCs ‘ functional analyses reveal how adipogenesis causes visceral adipose tissue to accumulate in middle- and early-age.
RESULTS
Male mice gained body weight at the age of 12 because their visceral sites, particularly at the visceral site, were more in the body. By contrast, female mice only had moderate body weight gain.
More than 80 % of adipocytes were newly generated in the visceral adipose tissue of 12-month-old male mice after receiving a standard chow diet, according to research using lineage-tracing mouse models.
Middle-aged mice also developed adipocyte hypotrophy, visceral adiposity, reduced energy expenditure, and insulin resistance as a result of this extensive adipogenesis. 3D profiling of APC transplants quantitatively showed that APCs in middle-aged mice had a much higher adipogenic rate than those in young mice, indicating that these APCs cell-autonomously obtain higher adipogenic potential.
A new committed preadipocyte population that is age-enriched ( CP-A ) exists in both the mouse and the human population, according to single-cell RNA sequencing of APCs. CP-As demonstrated high proliferation and differentiation capabilities both in vitro and in vivo.
The number of CP-As in the visceral adipose tissue increased when mice were 9 months old, peaked when they were 12 months old, and then sharply declined when they were 18 months old. Leukemia-inhibitory factor ( LIFR ) was identified as a potential functional marker of CP-A. According to genetic manipulation and pathological inhibition, LIFR is required for CP-A adipogenesis.
The inhibition of LIFR did not affect the adipogenesis of young APCs, indicating that LIFR signaling is specifically required for CP-As. Finally, early aging and ongoing treatment with a LIFR inhibitor prevented mice’s visceral fat from expanding.
CONCLUSION
Our research incorporates in-vivo lineage-tracing, 3D profiling of transplants, and single-cell RNA sequencing, demonstrating how significantly APCs ‘ adipogenesis affects the visceral expansion of middle-aged tissues.
The discovery of CP-A as an age-specific APC population, along with the validation of its high adipogenic capacity both in vitro and in vivo, and the identification of LIFR signaling as a CP-A–specific adipogenic mechanism enhance our understanding of the early aging process in fat tissue.
Our research revealed that despite having a low turnover rate of adipocytes in young adults, adipogenesis is unlocked in middle age.
APCs are different from the majority of other adult stem cells, which typically exhibit a decreased capacity to proliferate and differentiate with age due to the increase of their adipogenic capacity.
Moreover, as the enhancement of adipogenesis and emergence of the CP-A population happens primarily in the male visceral adipose tissue and only during middle age and early aging, these events are location, stage, and sex specific.
Our findings provide a fundamental understanding of the pathophysiology of age-related metabolic disorders, which may have significant implications for preventing and treating age-related diseases and promoting healthy aging.
