ageing update

It is painful to read Nutrition papers proposing that some element of the diet is affecting expectation of life and that in the olden golden days life expectation was better. This is palpably not the truth.
In developed countries the expectation of life has increased over the last 200 years from the late 40s to late 80s.
The benefits of sanitation, nutrition, better housing , and education have been central to this progress . More recently the benefits of improved medical care including vaccination and antibiotics have been very important.
Much of the improvement is due to most people surviving the former vicissitudes of diseases in youth and middle age.
Now the elderly live longer.
An extensively studied model of cellular ageing is the cultured human diploid fibroblast, which divides only a finite number of times before entering a state of ‘replicative senescence’ (this number is known as the Hayflick limit). Although senescence is commonly attributed to simple telomere erosion, there is remarkable cell-to-cell heterogeneity in division potential.
There is evidence that the rate of telomere shortening is strongly affected by oxidative stress, and that an important source of damage-inducing ‘free radicals’(reactive oxygen species) is the intracellular population of mitochondria, particularly those that are themselves damaged by random mutation. As a result, a mathematical model was developed that showed how the heterogeneity of cell senescence can be explained by the synergy of multiple mechanisms (oxidative damage, telomere shortening and the stochastic nature of mutation to mitochondrial and nuclear DNA). These modelling predictions prompted the experimental study of a role for mitochondrial dysfunction in senescence”,
Damage which may contribute to ageing
DNA damage (genome instability)
Somatic mutations (copying errors, imperfect repair)
Telomere shortening
Chromosome rearrangements
Mitochondrial-DNA mutations
Gene disruption by viruses, transposons etc
Aberrant epigenetic modifications RN A damage
Transcription errors
Aberrant splicing
Protein damage
Synthesis errors
Aberrant post-translational modifications
Aberrant aggregation
Impaired protein turnover (catabolism)
Membrane damage

Kirkwood 2008 a systematic look at an old problem Nature vol 451 pp 644-647

Martin Eastwood
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