Aging is happening to all of us but what if we’ve been talking about it the wrong way?
With the global population getting older, scientists and clinicians are realizing something important: we need clearer language to describe what aging actually is, what’s normal, and when it turns into disease.
That’s where ICCARP comes in.
Following the World Health Organization’s move to formally classify age-related causes of disease, the International Consortium to Classify Ageing-related Pathologies (ICCARP) was established in 2023, led by Cardiff Metropolitan University. Its mission is simple but ambitious:
👉 create a shared, precise language for aging so researchers, clinicians, and policymakers are finally speaking the same biological language.
And one word caused more confusion than almost any other:
🧬 Senescence
Let’s break it down clearly, simply, and without the jargon overload.
What Is “Normative Aging”?
Not everyone ages the same way and that’s normal.
Instead of vague terms like “average” or “typical” aging, ICCARP uses:
Normative Aging
Defined as the expected trajectory of aging based on population data.
Normative aging may include:
- Gradual functional decline
- Reduced resilience
- Age-related cellular, tissue, or organ changes
Importantly, normative aging is not automatically pathological. It can involve senescence without disease.
So… What Exactly Is Senescence?
At its broadest level:
Senescence = a decline in normal function associated with chronological aging
These changes are influenced by genetics, environment, and lifestyle—and they shape how well the body maintains and repairs itself over time.
Historically, senescence was seen as inevitable. Today, we know it can be:
- Adaptive
- Neutral
- Or harmful, depending on context
Cellular Senescence: When Cells Retire but Don’t Leave
Cellular senescence is a state where cells permanently stop dividing due to:
- Replicative exhaustion
- DNA damage
- Oxidative stress
- Nutrient deprivation
- Oncogene activation
This growth arrest is primarily regulated by CDK inhibitors p16 and p21.
Senescent cells don’t just sit quietly they change:
- Altered shape and metabolism
- Telomere dysfunction or macromolecular damage
- A pro-inflammatory secretory profile known as SASP (senescence-associated secretory phenotype)
These features distinguish senescent cells from quiescent or terminally differentiated cells.
Key insight: Senescent cells exist at all life stages.
Acute vs. Chronic Senescence: Same Process, Different Outcome
🟢 Acute Senescence (Helpful)
- Occurs during development and tissue repair
- Promotes wound healing
- Helps suppress early tumor formation
- Triggers immune clearance once its job is done
This form is physiological and essential for tissue integrity.
🔴 Chronic Senescence (Harmful)
- Senescent cells accumulate
- Immune clearance fails
- Chronic inflammation increases
- Organ function declines
This persistent state contributes to aging-related pathologies.
Physiological vs. Pathological Senescence
Physiological Senescence
A normal, necessary process involved in:
- Development
- Tissue repair and regeneration
- Homeostasis
- Tumor suppression (especially early in life)
It is usually temporary and purpose-driven.
Pathological Senescence
Occurs when senescence becomes:
- Persistent
- Dysregulated
- Functionally damaging
It may involve:
- Chronic inflammation
- Fibrosis
- Stem cell exhaustion
- Impaired regeneration
- Tumorigenesis
📌 Example:
In kidney aging, p21⁺ senescent epithelial cells reduce regenerative capacity and promote fibrosis, contributing to declining renal function with age and after injury.
Scaling Up: Senescence Across the Body
🧩 Tissue Senescence
An age-related decline in tissue structure or function, driven by:
- Senescent cell accumulation
- Mitochondrial dysfunction
- Altered proteostasis
- ECM remodeling
Organ Senescence
Occurs when senescent tissues impair organ function.
Examples:
- Brain senescence → cognitive decline
- Cardiac hypertrophy → short-term adaptation, long-term risk
- Post-menopausal uterine senescence → normative, not disease
🧠 Systems Senescence
When interconnected systems like the immune system lose efficiency, leading to:
- Immune dysfunction
- Increased inflammation
- Higher disease susceptibility
🧍 Organismal Senescence
The integrated decline of physiological function across the entire organism, marked by:
- Reduced stress resilience
- Impaired repair mechanisms
- Increased disease vulnerability
- Lifespan limitation
Organismal senescence reflects the cumulative impact of cellular, tissue, organ, and system-level changes.
Why These Definitions Matter
Words shape medicine.
Without clear terminology:
- Aging gets mistaken for disease
- Research becomes fragmented
- Clinical decisions lose precision
ICCARP’s standardized definitions aim to:
🧬 unify aging research
🧬 improve diagnostics
🧬 align clinical practice with biology
🧬 support better public health planning
As populations age worldwide, clarity isn’t optional—it’s essential.
The Big Takeaway
Aging isn’t one thing.
Senescence isn’t always harmful.
And decline doesn’t automatically mean disease.
By defining what’s normative, physiological, and pathological, ICCARP helps shift aging science from confusion to clarity and from reaction to prevention.
Understanding aging is the first step toward aging better.
References (PubMed)
- Calimport SRG, Bentley BL. Aging classified as a cause of disease in ICD-11.
- Short E, ICCARP, Calimport S, Bentley B. Defining an ageing-related pathology, disease or syndrome: International Consensus Statement. Geroscience. 2024.
- Di Micco R, Krizhanovsky V, Baker D, d’Adda di Fagagna F. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat Rev Mol Cell Biol
-
The Senescence-Associated Secretory Phenotype (SASP) in the Challenging Future of Cancer Therapy and Age-Related Diseases
(Note: ICCARP consensus letter provides definitions; multiple concepts are supported across foundational senescence literature.)