Molecular Biology

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: atelenti@humanlongevity.com (A.T.), bperkins@humanlongevity.com (B.A.P.), jcventer@jcvi.org (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