IL-11 and Healthspan Extension | Rejuventech

Introduction to Critical Pathways in Aging

Aging is a complex process involving several critical signaling pathways, including ERK, AMPK, and mTORC1. Inflammation is a central hallmark of aging, contributing to various age-related diseases and conditions. This study focuses on IL-11, a pro-inflammatory cytokine from the IL-6 family, and its impact on healthspan and lifespan. Researchers hypothesized that inhibiting IL-11 could mitigate age-associated pathologies and extend lifespan.

The Importance of Chronic Inflammation in Aging

Chronic sterile inflammation is increasingly recognized as a key factor in aging. Aging is associated with a dysfunctional immune system, characterized by immunosenescence and thymic involution, alongside inappropriate activation of innate immune genes such as IL-6. Pro-inflammatory signaling factors like NF-κB and JAK–STAT3 are specifically implicated in aging. Inhibiting these pathways has shown potential in alleviating age-related dysfunction.

IL-11 and Aging Pathologies

IL-11 plays a significant role in age-associated pathologies. It can activate both the ERK–mTORC1 and JAK–STAT3 pathways, contributing to metabolic decline, multi-morbidity, and frailty in old age. Researchers found that IL-11 is upregulated in older individuals, further supporting its role in senescence, a hallmark of aging.

Key Findings

1. IL-11 Upregulation with Age: IL-11 expression increases with age, contributing to harmful signaling pathways. This upregulation is seen across various tissues, including the liver, visceral white adipose tissue (vWAT), and muscle.
2. Deletion of IL-11: Deleting Il11 or its receptor Il11ra1 in mice protected against metabolic decline, reduced multi-morbidity, and frailty, and improved muscle function.
3. Anti-IL-11 Therapy: Administering anti-IL-11 antibodies to aged mice improved metabolism, muscle function, and reduced aging biomarkers. This therapy extended the median lifespan of male mice by 22.5% and female mice by 25%.

Mechanisms of IL-11 in Aging

IL-11 affects multiple aging pathways, including ERK, AMPK, mTOR, and JAK–STAT3. The study shows that inhibiting IL-11 has pleiotropic benefits, modulating these pathways and reducing age-associated pathologies.

Impact on Metabolism

Inhibition of IL-11 in old mice resulted in metabolic benefits similar to those seen in young mice with WAT-specific deletion of Raptor. This includes lower body weight, reduced fat mass, and improved glucose tolerance and insulin sensitivity. IL-11 inhibition also preserved mitochondrial function and prevented the age-related decline in telomere length and mitochondrial DNA content.

Senescence and Tissue Health

IL-11 is linked with senescence, contributing to tissue fibrosis and other aging-related issues. Inhibiting IL-11 reduced senescence markers in various tissues, improved muscle strength, and reduced frailty. These benefits were apparent even in young mice, suggesting that IL-11 has a significant impact on metabolic health and tissue integrity.

Lifespan Extension

Inhibition of IL-11 significantly extended the lifespan of both male and female mice. The magnitude of lifespan extension remains to be fully determined, but current data suggest a more than 20% increase in median lifespan. Anti-IL-11 therapy was effective when administered in late life, indicating its potential for extending lifespan even when started later in life.

Cancer and Longevity

Cancer is a common cause of death in old mice. The study found that inhibition of IL-11 significantly reduced the incidence of age-related cancers. This supports the notion that IL-11 plays a role in tumorigenesis and tumor immune evasion. Clinical trials of anti-IL-11 in combination with immunotherapy to treat cancer are planned.

Potential for Human Health

Given the promising results in mice, IL-11 inhibition is proposed as a potential therapy for age-related diseases in humans. Anti-IL-11 therapies, currently in trials for fibrotic lung disease, may also benefit older adults by reducing inflammation and improving overall health.

Implications for Anti-Aging Therapies

This study highlights the potential of IL-11 inhibition as a powerful anti-aging therapy. By reducing chronic inflammation and improving metabolic health, IL-11 inhibitors could enhance both healthspan and lifespan in humans. The therapy's safety profile and ongoing clinical trials suggest it could be a viable option for extending human healthspan and lifespan.

Conclusion

The study demonstrates that IL-11 plays a critical role in age-related pathologies and lifespan. Inhibiting IL-11 has significant benefits for metabolic health, tissue integrity, and longevity. These findings suggest that anti-IL-11 therapy could be a promising approach to extend human healthspan and lifespan, providing a new avenue for anti-aging interventions.

Conclusion

Discover how inhibiting IL-11 can extend both healthspan and lifespan. IL-11, a pro-inflammatory cytokine, impacts age-related diseases and metabolic decline. Blocking IL-11 improves metabolism, reduces frailty, and significantly extends lifespan in mice. This study reveals the potential of IL-11 inhibition as a powerful anti-aging therapy, enhancing healthspan and lifespan by reducing chronic inflammation and improving metabolic health. With ongoing clinical trials, IL-11 inhibitors could become a viable option for extending human healthspan and lifespan, offering a promising future for anti-aging interventions.

In the meantime, here are a few proven, commercially-available products for improving wellness and increasing lifespan.

Recent research highlights several innovative therapies that show promise in enhancing wellness and extending lifespan. Cryotherapy, which involves exposing the body to extremely cold temperatures, is lauded for its ability to treat pain and inflammation, potentially improving overall health and longevity. Vibration plates, such as those available from LifetimeVibe and VibePlate, use micro-vibrations to stimulate muscles, enhance circulation, and aid in calorie burning, contributing to better physical health. Red light therapy (RLT) is another emerging treatment, showing efficacy in reducing wrinkles, redness, acne, and scars, making it a valuable tool in the anti-aging arsenal.

Sources

1. PinnacleCare - Healthspan versus Longevity: Building a Strategy to Age Well
2. NCBI - Energetic Interventions for Healthspan and Resiliency
3. López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2022). Hallmarks of aging: an expanding universe. Cell, 186, 243–278.
4. Fabian, D. K., Fuentealba, M., Dönertaş, H. M., Partridge, L., & Thornton, J. M. (2021). Functional conservation in genes and pathways linking ageing and immunity. Immun. Ageing, 18, 23.
5. Selman, C. et al. (2009). Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science, 326, 140–144.
6. Salminen, A., & Kaarniranta, K. (2012). AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res. Rev., 11, 230–241.
7. Slack, C. et al. (2015). The Ras–Erk–ETS-signaling pathway is a drug target for longevity. Cell, 162, 72–83.
8. Castillo-Quan, J. I. et al. (2019). A triple drug combination targeting components of the nutrient-sensing network maximizes longevity. Proc. Natl Acad. Sci. USA, 116, 20817–20819.
9. Furman, D. et al. (2019). Chronic inflammation in the etiology of disease across the life span. Nat. Med., 25, 1822–1832.