SENS

The Framework

SENS (Strategies for Engineered Negligible Senescence) is a framework for defeating biological aging developed by Aubrey de Grey. Rather than trying to slow aging or understand all its mechanisms, SENS focuses on identifying and repairing the damage that accumulates over time.

The key insight is that aging isn't a single process but the accumulation of various types of molecular and cellular damage. Fix the damage periodically, and the body can be maintained indefinitely.

The Seven Categories of Damage

SENS identifies seven categories of aging damage, each requiring different repair strategies:

1. Cell loss and atrophy: Cells die and aren't replaced, leading to tissue decline. Solution: stem cell therapies and growth factors.

2. Cancerous cells: Cells with dangerous mutations that could become cancer. Solution: remove telomere-lengthening machinery to limit cancer's ability to grow indefinitely.

3. Mitochondrial mutations: Damage to mitochondrial DNA reduces cellular energy. Solution: copy essential mitochondrial genes to the nucleus.

4. Death-resistant cells: Senescent cells that should die but don't, secreting harmful factors. Solution: senolytics to selectively destroy these cells.

5. Extracellular crosslinks: Proteins become chemically linked, stiffening tissues. Solution: drugs or enzymes that break these crosslinks.

6. Extracellular aggregates: Junk accumulates outside cells (like amyloid plaques). Solution: immune therapies or enzymes to clear the aggregates.

7. Intracellular aggregates: Junk accumulates inside cells (like lipofuscin). Solution: enzymes that can digest these materials.

Progress and Status

Each category has seen meaningful research progress:

• Senolytics: Multiple drugs in Phase 2 human trials. Unity Biotechnology and other companies are testing senolytic therapies for specific age-related conditions.
• Amyloid clearance: FDA-approved treatments (lecanemab, donanemab) now exist for Alzheimer's, validating the approach of clearing extracellular aggregates.
• Stem cell therapies: Increasingly sophisticated, with cellular reprogramming showing the ability to reverse aging markers in mammalian tissues.
• Mitochondrial therapies: Gene therapy approaches to address mitochondrial mutations are advancing.
• Crosslink breakers: Earlier stage, but computational chemistry and AI-driven drug design are accelerating the search.

No single category is "solved," but the approach is being validated across multiple fronts simultaneously.

AI as Accelerant

AI is emerging as a powerful accelerant for the SENS agenda. Machine learning models can screen drug candidates, predict molecular interactions, and identify promising therapeutic targets at speeds impossible for human researchers alone. The convergence of AI and longevity research may compress timelines for addressing all seven damage categories.

The Repair Paradigm

SENS represents a shift from treating aging as inevitable to treating it as an engineering problem. We don't need to understand every detail of how damage accumulates—we just need to fix it before it causes problems.