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  • Review Article
  • Published:

Mechanisms of aging: public or private?

Nature Reviews Genetics volume 3, pages 165–175 (2002)Cite this article

Key Points

  • Much of the experimental work on ageing is done in invertebrate model organisms. However, for work in these organisms to be relevant to studies of human ageing, we need to know which mechanisms of ageing are 'public' (those shared across different, distantly related evolutionary lineages) and which are 'private' (those peculiar to particular evolutionary lineages).

  • Although there is no obvious programme for ageing, two events — caloric restriction and reduced reproductive rate — slow down the rate of ageing throughout the animal kingdom. How they do this is not understood, but their widespread effects indicate that common mechanisms might be at work across different evolutionary lineages.

  • Two evolutionary theories of ageing — the mutation-accumulation and trade-off theories — have different implications for the conservation of the mechanisms of ageing over large evolutionary distances. Experimental tests of these theories in flies support the trade-off model of ageing and indicate that a trade-off occurs between early fecundity and the subsequent rate of ageing.

  • Ageing mutants in invertebrate model organisms have been generated to investigate the mechanisms that underlie ageing. These studies have identified an evolutionary conserved neuroendocrine system, the insulin/IGF (insulin-like growth factor) signalling pathway, which apparently functions to accelerate ageing. The effect of this pathway on ageing can be explained as being part of a trade-off with fitness-enhancing pleiotropic effects that are subject to insulin/IGF-pathway modulation in response to changes in nutrition.

  • The challenges now are to unravel the mechanisms of ageing in invertebrate model organisms, and to determine if they are shared with those in other evolutionary lineages, especially mammals.

Abstract

Ageing — the decline in survival and fecundity with advancing age — is caused by damage to macromolecules and tissues. Ageing is not a programmed process, in the sense that no genes are known to have evolved specifically to cause damage and ageing. Mechanisms of ageing might therefore not be expected to be as highly conserved between distantly related organisms as are mechanisms of development and metabolism. However, evidence is mounting that modulators of the rate of ageing are conserved over large evolutionary distances. As we discuss in this review, this conservation might stem from mechanisms that match reproductive rate to nutrient supply.

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Figure 1: Two models of antagonistic pleiotropy.
Figure 2: Extended lifespan in daf-2 mutant Caenorhabditis elegans.
Figure 3: Insulin/IGF signalling pathways in Caenorhabditis elegans and Drosophila.
Figure 4: Neuroendocrine regulation of ageing.

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Acknowledgements

The authors acknowledge support for their work from the Biotechnology and Biological Sciences Research Council, the Natural Environment Research Council, the European Union FP5 and the Royal Society.

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Authors and Affiliations

  1. Department of Biology, University College London, Gower Street, London, WC1E 6BT, UK

    Linda Partridge & David Gems

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DATABASES

LocusLink

Akt1

chico

Dp110

growth hormone

growth hormone receptor

Igf1

Inr

Insr

Insrr

ovo

Pit1

prolactin

Prop1

thyroid-stimulating hormone

Mouse Genome Informatics

Ames

Ghrhr lit

Snell

OMIM

Huntington disease

leprechaunism

type II (non-insulin-dependent) diabetes

WormBase

AAP-1

age-1

AKT-1

AKT-2

DAF-2

DAF-12

daf-16

INS-1

PDK-1

FURTHER INFORMATION

Alfred Russel Wallace

David Gems' laboratory

Ageing as a global challenge in the new millennium

Ageing genes: gerontogenes

Linda Partridge's laboratory

Glossary

PEROXIDATION

A type of oxidation that involves the addition of oxygen to, for example, unsaturated fatty acids.

PROTEIN CARBONYL

A protein that contains oxygen that is linked by a double bond to carbon, resulting from protein oxidation.

BIOGERONTOLOGY

The study of biological processes that give rise to ageing.

PLEIOTROPY

The capacity of different alleles of a gene to affect more than one aspect of a phenotype.

INBREEDING DEPRESSION

This occurs when deleterious, recessive alleles become homozygous in the progeny of matings between relatives, causing reduced fitness among these individuals.

DAUER LARVA

A developmentally arrested, immature, long-lived and non-feeding form of Caenorhabditis elegans that forms under conditions of food scarcity and high population density, and that resumes development if food levels increase.

FORWARD GENETICS

A genetic analysis that proceeds from phenotype to genotype: for example, by positional cloning or candidate-gene analysis.

CORPORA ALLATA

Endocrine glands located in the head of insects.

AMPHIDS

Paired openings in the nose of nematodes that act as smell and taste organs.

BIODEMOGRAPHY

The study of age-specific mortality and fecundity rates and their biological determinants.

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Partridge, L., Gems, D. Mechanisms of aging: public or private?. Nat Rev Genet 3, 165–175 (2002). https://doi.org/10.1038/nrg753

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