| id |
b996a863-1c98-4a77-842c-4008d596029f |
| user_id |
8684964a-bab1-4235-93a8-5fd5e24a1d0a |
| job_id |
wvptnahr-9268 |
| base_model_name |
xevyo |
| base_model_path |
/home/sid/tuning/finetune/backend/output/xevyo-bas /home/sid/tuning/finetune/backend/output/xevyo-base-v1/merged_fp16_hf... |
| model_name |
longevity of C. elegans m |
| model_desc |
longevity of C. elegans mutants |
| model_path |
/home/sid/tuning/finetune/backend/output/wvptnahr- /home/sid/tuning/finetune/backend/output/wvptnahr-9268/merged_fp16_hf... |
| source_model_name |
xevyo |
| source_model_path |
/home/sid/tuning/finetune/backend/output/xevyo-bas /home/sid/tuning/finetune/backend/output/xevyo-base-v1/merged_fp16_hf... |
| source_job_id |
xevyo-base-v1 |
| dataset_desc |
This study delivers a deep, mechanistic explanatio This study delivers a deep, mechanistic explanation of how changes in lipid biosynthesis—specifically in fatty-acid chain length and saturation—contribute directly to the extraordinary longevity of certain C. elegans mutants, especially those with disrupted insulin/IGF-1 signaling (IIS). By comparing ten nearly genetically identical worm strains that span a tenfold range of lifespans, the authors identify precise lipid signatures that track strongly with lifespan and experimentally confirm that altering these lipid pathways causally extends or reduces lifespan.
Its central insight:
Long-lived worms reprogram lipid metabolism to make their cell membranes more resistant to oxidative damage, particularly by reducing peroxidation-prone polyunsaturated fatty acids (PUFAs) and shifting toward shorter and more saturated lipid chains.
This metabolic remodeling lowers the substrate available for destructive free-radical chain reactions, boosting both stress resistance and lifespan.
🧬 Core Findings, Explained Perfectly
1. Strong biochemical patterns link lipid structure to lifespan
Across all strains, two lipid features were the strongest predictors of longevity:
A. Shorter fatty-acid chain length
Long-lived worms had:
more short-chain fats (C14:0, C16:0)
fewer long-chain fats (C18:0, C20:0, C22:0)
Average chain length decreased almost perfectly in proportion to lifespan.
B. Fewer polyunsaturated fatty acids (PUFAs)
Long-lived mutants had:
sharply reduced PUFAs (EPA, arachidonic acid, etc.)
dramatically lower peroxidation index (PI)
fewer double bonds (lower DBI)
These changes make membranes much less susceptible to lipid peroxidation damage.
2. Changes in enzyme activity explain the lipid shifts
By measuring mRNA levels and inferred enzymatic activity, the study shows:
Downregulated in long-lived mutants
Elongases (elo-1, elo-2, elo-5) → shorter chains
Δ5 desaturase (fat-4) → fewer PUFAs
Upregulated
Δ9 desaturases (fat-6, fat-7) → more monounsaturated, oxidation-resistant MUFAs
This combination produces membranes that are:
just fluid enough (thanks to MUFAs)
much harder to oxidize (thanks to less PUFA content)
This is a perfect, balanced redesign of the membrane.
3. RNAi experiments prove these lipid changes CAUSE longevity
Knocking down specific genes in normal worms produced dramatic effects:
Increasing lifespan
fat-4 (Δ5 desaturase) RNAi → +25% lifespan
elo-1 or elo-2 (elongases) RNAi → ~10–15% lifespan increase
Combined elo-1 + elo-2 knockdown → even larger increase
Reducing lifespan
Knockdown of Δ9 desaturases (fat-6, fat-7) slightly shortened lifespan
Stress resistance matched the lifespan effects
The same interventions boosted survival under hydrogen peroxide oxidative stress, confirming that resistance to lipid peroxidation is a key mechanism of longevity.
4. Dietary experiments confirm the same mechanism
When worms were fed extra PUFAs like EPA or DHA:
lifespan dropped by 16–24%
Even though these fatty acids are often considered “healthy” in humans, in worms they create more oxidative vulnerability, validating the model.
5. Insulin/IGF-1 longevity mutants remodel lipids as part of their longevity program
The longest-lived mutants—especially age-1(mg44), which can live nearly 10× longer—show the greatest lipid remodeling:
lowest elongase expression
lowest PUFA levels
highest MUFA-producing Δ9 desaturases
This suggests that IIS mutants extend lifespan partly through targeted remodeling of membrane lipid composition, not just through metabolic slowdown or stress-response pathways.
💡 What This Means
The core conclusion
Longevity in C. elegans is intimately connected to reducing lipid peroxidation, a major source of cellular damage.
Worms extend their lifespan by:
shortening lipid chains
reducing PUFA content
elevating MUFAs
suppressing enzymes that create vulnerable lipid species
enhancing enzymes that create stable ones
These changes:
harden membranes against oxidation
reduce chain-reaction damage
increase survival under stress
extend lifespan significantly
**This is one of the clearest demonstrations that lipid composition is not just correlated with longevity—
it helps cause longevity.**... |
| dataset_meta |
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| dataset_path |
/home/sid/tuning/finetune/backend/output/wvptnahr- /home/sid/tuning/finetune/backend/output/wvptnahr-9268/data/wvptnahr-9268.json... |
| training_output |
null |
| status |
completed |
| created_at |
1764877638 |
| updated_at |
1764886292 |
| source_adapter_path |
NULL |
| adapter_path |
/home/sid/tuning/finetune/backend/output/wvptnahr- /home/sid/tuning/finetune/backend/output/wvptnahr-9268/adapter... |
| plugged_in |
False |