Why faster isn’t always better for studying human muscle ageing.
Article
Ruparelia, AA, Salavaty, A, Barlow, CK, Lu, Y, Sonntag, C, Hersey, L, Eramo, MJ, Krug, J, Reuter, H, Schittenhelm, RB, Ramialison, M, Cox, A, Ryan, MT, Creek, DJ, Englert, C & Currie, PD 2024, ‘The African killifish: A short-lived vertebrate model to study the biology of sarcopenia and longevity’, Aging Cell, vol. 23, no. 1, e13862. https://doi.org/10.1111/acel.13862
Funding
- National Health and Medical Research Council
- Monash University
- The Winston Churchill Memorial Trust
- The Australian Regenerative Medicine Institute is supported by funds from the State Government of Victoria and the Australian Federal Government
Background
The African turquoise killifish (Nothobranchius furzeri) lives just four to six months in captivity—the shortest span of any vertebrate model. Despite this rapid lifecycle, killifish develop many ageing hallmarks also seen in longer-lived species, making them tempting for high-speed trials of age-related conditions.
Key terms
- African turquoise killifish (Nothobranchius furzeri): A short-lived fish used in ageing research due to its rapid life cycle and development of ageing hallmarks.
- Sarcopenia: The age-related loss of muscle mass and strength, linked to frailty, falls and reduced quality of life in older adults.
- Stem cells: Specialised cells that repair and regenerate muscle tissue. Their numbers and function decline with age.
- Mortality deceleration: A slowdown in the rate of death in very old age—seen in some animals, but not typically in humans.
- Sirt1 (Sirtuin 1): A protein involved in cellular stress responses and energy regulation. It’s activated during calorie restriction and has been linked to longevity.
- Resveratrol: A natural compound found in foods like red grapes. It activates Sirt1 and has been studied for its potential anti-ageing effects.
- Triglycerides: A type of fat stored in the body. Killifish that better manage triglyceride use tend to live longer.
- Oxidative stress: Damage caused by unstable molecules (free radicals) in cells. Reducing this damage is key to healthy ageing.
- Mitohormesis: A concept where mild stress on mitochondria (cellular energy centres) triggers beneficial effects, like improved metabolism and antioxidant defences.
Study overview
At Monash University’s FishCore facility, researchers tested whether African killifish could model sarcopenia—the gradual loss of muscle mass and strength with age.
They tracked muscle changes from youth to ‘extreme old age’ across the fish’s short lifespan. Scientists euthanised fish at set ages to examine their muscle tissue under the microscope. Using a blend of molecular tests and imaging, the team looked for signs of ageing—shrinking fibres, protein breakdown and shifts in metabolism—to see if these rapid-ageing fish could help us understand human muscle decline.
Findings included:
- Signs of sarcopenia: Killifish showed shrinking fibres, fewer stem cells and nerve loss—key features of human muscle ageing.
- Late-life rebound: In extreme old age, some fish regained muscle size and boosted protein recycling, and their mortality rates slowed—a phenomenon called mortality deceleration.
- Fat-fuel shifts: Older fish stored more triglycerides and tapped fat stores more efficiently, linking lipid metabolism to longer lifespans.
- Stress-response boost: Mild energy stress activated Sirt1, which helped to:
- Reduce oxidative damage
- Clear out old proteins
- Maintain healthy muscle
- Boost energy production
- Drug mimicry: Treating aged fish with resveratrol (a Sirt1 activator) reproduced these metabolic changes—hinting at a potential way to support healthy ageing.
The researchers concluded that killifish are a practical model for studying sarcopenia, as they display key features of human muscle-ageing. Yet paradoxically, the study also suggests that ageing might not be an irreversible, linear decline—in some animals, built-in recovery systems may activate later in life.
Why killifish fall short for human sarcopenia
- Different muscle biology: Fish fibres and repair systems aren’t the same as ours. Human sarcopenia is shaped by lifestyle, chronic disease and environment—factors a lab tank can’t replicate.
- Recovery humans don’t experience: In killifish, muscle features bounced back; in people, strength and mass only worsen over decades.
- A timeline too compressed to capture complexity: Killifish age in months; human sarcopenia unfolds over decades. This speed run misses slow-burn interactions.
- A narrow metabolic focus: The study zeroed in on Sirt1 and fat metabolism, but muscle ageing involves dozens of pathways—from inflammation to hormone regulation.
- Ethical concerns: Although fish are sentient vertebrates, they often lack strict welfare protections. Invasive studies with limited human relevance raise serious ethical questions.
Better ways to study sarcopenia
When we want human-relevant insights, these cutting-edge methods truly reflect our biology:
- 3D muscle cultures and organoids: Lab-grown human ‘mini-tissues’ that age under controlled conditions—no animals required.
- Muscle-on-a-chip: Microfluidic devices simulate real human muscle fibres, letting scientists watch ageing and test therapies in real time.
- Long-term cohort studies: Projects like the UK Biobank track diet, exercise and disease over years to reveal real-world drivers of sarcopenia.
- Wearable imaging and trackers: MRI and DXA scans alongside fitness devices give precise, non-invasive measures of muscle decline in volunteers.
- In silico modelling: Computer simulations can integrate multiple ageing pathways—fast, cost-effective and entirely animal-free.
Bottom line
Killifish bring speed but sacrifice accuracy. Although they spark valuable questions, their late-life muscle rebound undermines their value as a model for the irreversible, decades-long decline seen in humans.
To truly tackle sarcopenia and promote healthy ageing, we must choose models rooted in human biology. With ethical, human-relevant technologies now available, it’s time to retire outdated animal models and invest in research built for people, not fish.