MODULE 02 · 60 min

The Hallmarks of Aging

Twelve interconnected mechanisms that drive cellular and organismal decline.

In progress

Quiz 0/3

Core summary

Scientists have identified about a dozen biological processes that drive aging — things like DNA damage piling up, cells losing the ability to clean themselves, and mitochondria (the cell's batteries) wearing out. They're connected, which is why one intervention like exercise can help many of them, and why no single pill is likely to be a fountain of youth.

Topics covered

01Genomic instability and DNA damage accumulation
02Telomere attrition and replicative senescence
03Epigenetic alterations (methylation drift)
04Loss of proteostasis and autophagy decline
05Disabled macroautophagy
06Deregulated nutrient sensing (IGF-1, mTOR, AMPK, sirtuins)
07Mitochondrial dysfunction
08Cellular senescence and the SASP
09Stem cell exhaustion
10Altered intercellular communication and inflammaging
11Chronic inflammation
12Dysbiosis

Learning objectives

→Recall the 12 hallmarks framework (López-Otín 2023).
→Distinguish primary, antagonistic, and integrative hallmarks.
→Map common interventions (exercise, rapamycin, senolytics, metformin) to specific hallmarks.
→Explain why hallmarks are interconnected — and why single-target therapies often disappoint.

Key takeaways

→Aging is not one process; it's a network of feedback-coupled mechanisms.
→Most validated interventions hit several hallmarks at once (exercise, fasting, sleep).
→Senescence and inflammaging are emerging as the most druggable nodes.

Graded claims

Senescent cell burden increases with age in human tissue

Clinically established — Replicated across multiple tissue atlases.

Epigenetic clocks estimate biological age

Supported, context-specific — Strong correlations; causal status and reversibility debated.

Inflammaging contributes to multimorbidity

Supported, context-specific — Robust mechanistic and observational support.

All 12 hallmarks are independently druggable

Plausible, unproven in humans — Many lack validated human-grade modulators.

Quick check

1. Which hallmark covers chronic, low-grade systemic inflammation?

2. Which intervention has been shown to extend lifespan in mice across multiple labs?

3. Senescence-associated secretory phenotype (SASP) primarily contributes to: