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news-review:dynamics-of-an-aging-genome

Dynamics of an Aging Genome

20160614
* Amalio Telenti, 1,2, * Brad A. Perkins, 1, * and J. Craig Venter, 1,2, *
1 Human Longevity Inc., San Diego, CA 92121, USA
2 J. Craig Venter Institute, La Jolla, CA 92037, USA
*Correspondence: [email protected] (A.T.), [email protected] (B.A.P.), [email protected] (J.C.V.)
http://dx.doi.org/10.1016/j.cmet.2016.06.002

Takeaway:

Individuals may have a “genome burden”, which includes common and rare variant genes that accelerate aging through disease. Centenarians seem to live longer because they have a lower prevalence of these genes. “It is tempting to speculate that the dynamic process of decay of the somatic genome may be a stronger predictor of aging than hard-coded features of the germline genome.” The article fails to state what percentage of the population have common and rare gene variants.

Ideas Presented:

  • “Common” frailty gene variants are defined as being prevalent in at least 1% allele frequency.
  • Of the first 10,000 genomes sequenced, over 50% of gene variants are observed only once.
  • Around 1000 “essential” genes are poorly tolerant of any mutation.
  • 277 genes at GenAge (http://genomics.senescence.info) are statistically more likely to be among the set of essential genes.
  • 4 genes in GenAge are specifically linked to aging in humans.
  • “We can speculate that all other genes in GenAge, identified through cellular/animal readouts, are less likely to be associated with ‘‘physiological aging’’ and more likely to be related to basic cellular mechanisms and functions.”
  • Another element of the genome burden is that the somatic genome also ages, undergoing macro and micro changes.
  • macro modifications include:
    - loss of an autosome in somatic cell lineage
    - loss of mitochondrial genomes
    - telomere shortening
  • Loss of Y chromosome was observed in up to 8% of individuals in a cohort of elderly males.
  • Micro changes (at DNA level), occur in blood, skin, neuron, and stem cell lineages. Changes can lead to somatic cell competition, where the fittest survive, including cancerous cells.

Marcos Reyes 2019/04/07 04:09

news-review/dynamics-of-an-aging-genome.txt · Last modified: 2019/07/17 03:34 by marcos