Model of ageing for Preclinical Research

Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide.

Aging is an intricate biological process leading to a progressive decline in the body's physiological functions. This results from a combination of cellular and molecular changes accumulating over time, such as DNA damage, mitochondrial dysfunction, and the accumulation of senescent cells. This process is highly individual, making biological age often different from chronological age.
Nutraceuticals are gaining significant attention in the field of aging due to their potential to counteract the age-related decline in physiological functions. These products, derived from food sources, are believed to provide health benefits beyond basic nutrition, often by targeting the underlying molecular and cellular hallmarks of aging.
At Vibiosphen, we provide a robust model of ageing in mouse to support the development of novel nutraceuticals. Our models are designed to generate clinically relevant data that help pharmaceutical, and biotechnology companies accelerate food supplement discovery.
 

Background of Model of ageing

This age-related functional decline affects virtually every organ system. The cardiovascular system stiffens, the immune system weakens (immunosenescence), and muscles are lost (sarcopenia). Cognitive abilities can diminish, hormone levels shift, and organs like the kidneys become less efficient. This overall decline reduces an individual's resilience to stress and disease, impacting both the length and quality of life.

To comprehensively assess aging, both globally and within specific organs like the liver, we offer a mouse model where a panel of distinct biomarkers can be investigated. These markers reflect key hallmarks of aging, including cellular senescence, oxidative stress, and systemic inflammation.

Rodent Models of ageing model

Animals (mouse/rat)

The decision to use an inbred or outbred strain depends on the specific research question. Inbred animals are for when you want to minimize all genetic variables and pinpoint the effect of a single factor. Outbred animals are for when you want to see how a factor affects a genetically varied population. 
    Inbred mice: C57BL/6, BALB/c mice.
    Inbred mice : SAM (senescence accelerated mice)
    Outbred mice: CD-1 (also known as ICR) mice, Swiss mice.
    Inbred rats: Fischer 344 (F344) rats
    Outbred rats: Sprague Dawley rats, Wistar rats.

Readouts in ageing Models

1. Cellular Senescence & Its Secretory Phenotype (SASP)
A critical aspect of senescent cells is their Senescence-Associated Secretory Phenotype (SASP), a pro-inflammatory cocktail of secreted factors that can drive chronic inflammation and tissue dysfunction.
o    Pro-inflammatory Cytokines: IL-6, IL-1β, TNF-α, and IL-8 (CXCL8)
o    Chemokines: CCL2 (MCP-1) and CXCL1 (GROα)
o    Growth Factors: VEGF and HGF, influencing angiogenesis and tissue repair/fibrosis.
o    Matrix Metalloproteinases (MMPs): Enzymes like MMP-3 and MMP-9 involved in extracellular matrix remodeling.

2. Oxidative Stress Markers
Oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, is a major contributor to cellular damage during aging.
o    TBARS (Thiobarbituric Acid Reactive Substances): widely recognized biomarker for lipid peroxidation, a destructive process targeting cell membranes. Elevated TBARS levels are strongly associated with increased oxidative stress and are considered a reliable indicator of chronological aging and age-related tissue damage.

3. Organ-Specific Senescence Markers (Liver Example)
o    Liver p16 (p16INK4a): This tumor suppressor protein plays a crucial role in cell cycle regulation, primarily by inducing cell cycle arrest. Increased p16 expression in the liver is a key hallmark of cellular senescence within hepatocytes and other resident liver cells. Its accumulation directly correlates with liver aging and is implicated in the progression of various chronic liver diseases.

4. Systemic Markers of Longevity and Cellular Maintenance
o    Serum SIRT6: Sirtuin 6 is a protein deacetylase involved in DNA repair, genome stability, and metabolism. Its serum levels can reflect the overall activity of cellular maintenance pathways.
o    Telomerase Serum Levels: Telomerase is an enzyme that maintains the length of telomeres. Telomere shortening is a key hallmark of cellular aging, and serum telomerase levels might offer insights into systemic cellular replicative capacity and aging.

5. Systemic Inflammaging & Organ Dysfunction Markers
The state of chronic, low-grade inflammation (inflammaging) is a characteristic of aging and can impact distant organs.
o    Plasma CXCL9: This chemokine has emerged as a crucial player in age-related cardiovascular pathologies, contributing to impaired vascular function, cardiac remodeling, and cardiac aging. Elevated plasma levels suggest systemic inflammatory processes affecting the cardiovascular system.
o    Renal Function Biomarkers: Renal function is strongly associated with aging and is a sensitive indicator of systemic health. Markers directly reflecting systemic senescence and inflammaging through their impact on kidney function include:
    Creatinine and Urea: Standard indicators of kidney filtration capacity.
    Kynurenine and Tryptophan: These are involved in the tryptophan-kynurenine pathway, which is implicated in inflammation, immune regulation, and neurodegeneration, with alterations observed during aging and chronic inflammation impacting renal health.

Why Choose Vibiosphen?

•    Proven expertise in preclinical research
•    Flexible and customized study designs adapted to sponsor requirements (see downloads available as example) 
•    Advanced facilities to ensure reliable and reproducible results (BSL2 and BSL3) 
•    Strong collaborations with pharmaceutical companies, biotech firms, and academic partners
Vibiosphen combines scientific excellence with industry know-how to deliver actionable preclinical data that drive innovation personal care and well being.
 

Contact Us

If you are developing new treatments or vaccines, Vibiosphen can help accelerate your research.
Contact us today to discuss your project and explore how our ageing models can support your development strategy. 
We will be pleased to facilitate your project by providing a customized study design to your project objectives.