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Cited by 131Genetics, Aging, and Longevity in Model OrganismsDietary Effects on HealthSirtuins and Resveratrol in Medicine

Calories or protein? The effect of dietary restriction on lifespan in rodents is explained by calories alone

Speakman, J.R., Mitchell, S.E., Mazidi, M.·2016·Experimental Gerontology
DOI 10.1016/j.exger.2016.03.011
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Abstract

Almost exactly 100years ago Osborne and colleagues demonstrated that restricting the food intake of a small number of female rats extended their lifespan. In the 1930s experiments on the impact of diet on lifespan were extended by Slonaker, and subsequently McCay. Slonaker concluded that there was a strong impact of protein intake on lifespan, while McCay concluded that calories are the main factor causing differences in lifespan when animals are restricted (Calorie restriction or CR). Hence from the very beginning the question of whether food restriction acts on lifespan via reduced calorie intake or reduced protein intake was disputed. Subsequent work supported the idea that calories were the dominant factor. More recently, however, this role has again been questioned, particularly in studies of insects. Here we review the data regarding previous studies of protein and calorie restriction in rodents. We show that increasing CR (with simultaneous protein restriction: PR) increases lifespan, and that CR with no PR generates an identical effect. None of the residual variation in the impact of CR (with PR) on lifespan could be traced to variation in macronutrient content of the diet. Other studies show that low protein content in the diet does increase median lifespan, but the effect is smaller than the CR effect. We conclude that CR is a valid phenomenon in rodents that cannot be explained by changes in protein intake, but that there is a separate phenomenon linking protein intake to lifespan, which acts over a different range of protein intakes than is typical in CR studies. This suggests there may be a fundamental difference in the responses of insects and rodents to CR. This may be traced to differences in the physiology of these groups, or reflect a major methodological difference between 'restriction' studies performed on rodents and insects. We suggest that studies where the diet is supplied ad libitum, but diluted with inert components, should perhaps be called dietary or caloric dilution, rather than dietary or caloric restriction, to distinguish these potentially important methodological differences.

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Authors
Speakman, J. R., Mitchell, S. E., & Mazidi, M.
Affiliations
  • University of Aberdeen (GB)
  • Chinese Academy of Sciences (CN)
Corresponding author
Speakman, J.R.
ORCID
Venue
Experimental Gerontology
Publisher
Elsevier BV
Published
2016-12
Volume
86
Pages
28-38
ISSN
0531-5565 (ISSN-L)
DOI
10.1016/j.exger.2016.03.011
OpenAlex
W2297798471
Cited by
131
References
103
Citations by year
2026: 5 · 2025: 16 · 2024: 10 · 2023: 8 · 2022: 14 · 2021: 23 · 2020: 14 · 2019: 14 · 2018: 11 · 2017: 14 · 2016: 2
FWCI
1.33
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Experimental Gerontology (publishedVersion)
  • PubMed (publishedVersion)
  • Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
Funders
  • Chinese Academy of Sciences (XDB13030000)
  • National Institutes of Health (R01AG043972)
  • Ministry of Science and Technology of the People's Republic of China
  • Royal Society
  • The World Academy of Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Physiology › Dietary Effects on Health
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Keywords
caloric restriction, protein restriction, lifespan extension, dietary restriction, rodents, insects, macronutrient composition, ad libitum feeding, dietary dilution
MeSH terms
Animals, Energy Intake, Female, Longevity, Male, Diet, Protein-Restricted, Caloric Restriction, Mice, Rats

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