IgG is an aging factor that drives adipose tissue fibrosis and metabolic decline
Aging is underpinned by pronounced metabolic decline; however, the drivers remain obscure. Here, we report that IgG accumulates during aging, particularly in white adipose tissue (WAT), to impair adipose tissue function and metabolic health. Caloric restriction (CR) decreases IgG accumulation in WAT, whereas replenishing IgG counteracts CR’s metabolic benefits. IgG activates macrophages via Ras signaling and consequently induces fibrosis in WAT through the TGF-β/SMAD pathway. Consistently, B cell null mice are protected from aging-associated WAT fibrosis, inflammation, and insulin resistance, unless exposed to IgG. Conditional ablation of the IgG recycling receptor, neonatal Fc receptor (FcRn), in macrophages prevents IgG accumulation in aging, resulting in prolonged healthspan and lifespan. Further, targeting FcRn by antisense oligonucleotide restores WAT integrity and metabolic health in aged mice. These findings pinpoint IgG as a hidden culprit in aging and enlighten a novel strategy to rejuvenate metabolic health.
https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00015-9
B cell null mice don’t get this. Even lymphocytes are not totally innocuous
CR reduces IgG…
can someone PDF
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Every cell in the human body has the same DNA sequence in it, but cells in different tissues have a distinct “identity” determined by their epigenetic profile; some genes are transcribed into protein while others are turned off, which facilitates their specific function in human biology. Scientists have begun to uncover that as the years go by the cells themselves begin to lose their highly specialized identity, which results in tissues and organs not doing their job anymore. Scientists can even track down these old cells by the proteins they produce:
"…increased spatial structural disorder and loss of cellular identity are universal signs of systemic aging, suggesting that spatial structural damage may be a primary cause of organ functional decline during aging.
The team also identified senescence-sensitive spots (SSS), which are structural regions in different tissues more susceptible to aging’s effects… areas closer to SSS exhibit higher tissue structural entropy and greater loss of cellular identity, indicating that SSS could be the nucleus of organ aging.
Notably, in immune organs, plasma cells, which are responsible for antibody synthesis, and cells with specific structures and functions, are the main components of the SSS microenvironment. The expression levels of immunoglobulin-related genes in these cells increase around SSS.
The study further discovered that immunoglobulin G (IgG) accumulates in multiple tissues and organs during aging in humans and mice, suggesting that IgG levels could serve as a new biomarker for aging. Moreover, IgG was found to directly induce aging in human and mouse macrophages and microglia, releasing inflammatory factors. Intriguingly, injecting IgG into young mice induced aging in multiple tissues and organs, demonstrating its potent aging effects."
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