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Molecular Therapy Nucleic Acids

Combination gene therapy extended lifespan in aged obese mice

Over 70 weeks of follow-up, aged obese mice given the combination had a 60% increase in lifespan compared with mice given control viral carriers.

Paper by Subhajit Pathak, Preethi Thozhukattu Valliyaparambil, Ramkumar Rajendiran, Sonal Amit, Giridhara Rao Jayandharan
Graphical abstract from Molecular Therapy Nucleic Acids
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Graphical abstract. Pathak et al., CC BY-NC-ND

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Interventions
Studied:
Experiments in mice

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
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Aged obese mice received a combination gene therapy in an animal experiment with a 70-week follow-up. Engineered viral carriers delivered human genes for fibroblast growth factor 21 and sirtuin 1, proteins involved in metabolism. Lifespan increased by 60% compared with mice given control viral carriers. The combination also improved metabolic measures, reduced fat buildup in the liver and reduced enlargement of the heart. Muscle function and quality improved.

In a separate experiment, aged lean mice received the fibroblast growth factor 21 gene alone. Over 50 weeks, they had less age-related frailty, moderate control of obesity and better muscle function. The researchers reported no signs of immune reactions linked to the viral carriers.

Why it matters

Age-related obesity and diabetes were targets of this approach. The authors suggest that combining the two genes may help extend both lifespan and the period of life spent in good health.

Caveats

The experiments tested gene therapy in aged obese and lean mice, leaving open whether it would provide similar benefits in people.

Where the evidence stands

FGF21 gene therapy

Mice: a single group. Cells, worms or flies and humans: nothing yet.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

  • 2 independent labs in 1 country
  • Funders: Division of Cancer Prevention, National Cancer Institute and 6 more
  • 9 of 9 findings with company ties

Immune response

Cells, worms or flies, mice and humans: replicated by independent labs.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 302 independent labs in 46 countries
  • 30 findings against
  • Funders: National Institutes of Health and others
  • 84 of 548 findings with company ties

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