A significant hallmark of aging is the increase in chronic, systemic, low-level inflammation. This phenomenon is so prevalent in aging organisms that it was dubbed “inflamm-aging” by Claudio Franceschi et al. nearly a quarter of a century ago. A recent study published in Nature has identified a novel target to help repress inflamm-aging in mice, resulting in a longer and more robust life.
Inflamm-aging
Inflammation is a necessary and beneficial process of the immune system, playing a critical role in combating infection and promoting wound healing. While inflammation’s benefits are typically seen as part of a transient immune response, poor regulation can lead to chronic inflammation, as observed in autoimmune diseases like rheumatoid arthritis, psoriasis, lupus, and numerous other conditions.
As organisms age, chronic low-level inflammation both drives and is intensified by various underlying mechanisms. These mechanisms include immune system dysregulation, cellular senescence, mitochondrial dysfunction, epigenetic changes, metabolic alterations, and other biological disruptions associated with aging. This vicious cycle of inflammation not only accelerates aging but also amplifies the decline in overall health, making it a central factor in age-related deterioration.
IL-11’s Role in Inflammation and Health
The study targeted a critical protein in the inflammatory response, IL-11, as a means to control chronic inflammation. IL-11 activates a complex of proteins often associated with lifespan modulation, known as ERK–AMPK–mTORC1. The research demonstrated a 20% extension of lifespan in mice following the deletion of this pro-inflammatory protein.
Unsurprisingly, the deletion of IL-11 led to reduced systemic inflammation as these experimental animals aged. Beyond its anti-inflammatory effects, the deletion also enhanced several metabolic functions, including improved glucose tolerance, increased insulin sensitivity, and reduced liver steatosis (fat accumulation). Furthermore, IL-11 deletion decreased inflammation and fibrosis in metabolic tissues, which are crucial for maintaining metabolic health and reducing the risk of age-related metabolic diseases. The degradation of metabolic control is a common feature of aging, and many existing pro-longevity interventions produce similar effects on these metabolic parameters.
The direct benefits to inflammation, fibrosis, and metabolism likely contributed to the improved physical condition of these mice. The authors noted significant enhancements in frailty measures; treated mice exhibited better physical performance, increased strength, and improved endurance as they aged. This improvement in healthspan is particularly noteworthy as extending lifespan is far more meaningful when those additional years are lived in good health.
Translating Findings for Human Benefit
The research suggests that targeting IL-11 signaling could be a promising strategy for developing drugs or therapies aimed at improving metabolic health, reducing age-related diseases, and extending human lifespan, similar to the effects observed in mice. Clinical trials would be necessary to determine the safety and efficacy of such treatments in humans, but this study provides a strong foundation for future anti-aging therapies centered on IL-11.
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