Authors: 
J.F. Allen, C.A. Allen
Category: 
Oral
Conference: 
Abstract: 

Why is senescence not inherited? We propose that ageing arises from redox chemistry in mitochondria in somatic cells and male gametes, while passive, "template" mitochondria are sequestered in female germ-lines, allowing an indefinite number of accurate mitochondrial replications without damage to the mitochondria, their genomes, or to the cells that carry them [1].

Mitochondrial function is synthesis of ATP by oxidative phosphorylation, coupled to respiratory electron transport. Respiratory electron transport requires a mitochondrial genetic system [2]. However, "incorrect" electron transfers produce free radicals that cause mutation, and their frequency is itself increased by mutation. The "powerhouse" function of mitochondria is therefore detrimental to the fidelity of their replication. Damage to somatic mitochondrial DNA may accumulate within, and determine, the life-span of individual organisms. Motility of one gamete is required for fertilisation, and requires ATP. It is proposed that female gametes, which are non-motile, repress mitochondrial oxidative phosphorylation, thus protecting mitochondrial DNA for faithful transmission between generations. Male gametes, in contrast, maximise energy production for motility by sacrificing mitochondrial DNA to electron transfer and its mutagenic by-products. Male gametes then make no contribution to the mitochondrial genome of the zygote: mitochondria are maternally inherited. This testable hypothesis may explain the prevalence of anisogametic sex as a device to allow an indefinite number of accurate replications of template mitochondria, from which all somatic mitochondria derive.

If the hypothesis is correct, we predict that senescence will be inherited by the progeny of reproductive cloning from somatic cells, as seen in "Dolly" the sheep, and other laboratory models [3]. We further predict that senescence will be promoted, not postponed, in allotopic mutants where the genes for respiratory-chain proteins are removed from mitochondria to the cell nucleus.

[1] Allen, J F (1996) Separate sexes and the mitochondrial theory of ageing. J. Theor. Biol. 180, 135-140.

 

[2] Allen, J F, Puthiyaveetil, S, Ström, J and Allen, C A (2005) Energy transduction anchors genes in organelles. BioEssays 27, 426-435.

 

[3] Allen, J F and Allen, C A (1999) A mitochondrial model for premature ageing of somatically cloned mammals. IUBMB Life 48, 369-372.

Keywords (Optional): 
aging
mitochondrion
oxidative-phosphoryation
sex
cloning