Presenters

Aging: Understanding it, Reversing it

Key Takeaways:

 

  • Cellular biomarkers are not aging, they can describe aspects of aging but do not illuminate the fundamental mechanisms
  • Very few patients exhibit “typical” clinical manifestations of disease
  • Aging is not ubiquitous, the germ line does not seem to age
  • Aging is not just entropy, but also a failure of maintenance
  • DNA repair and maintenance shows slowing with aging
  • The cascade is as follows: Cells die, cells divide, telomeres shorten, epigenetic expression changes, molecular turnover slows, molecular dysfunction increases, cellular dysfunction increases, tissue and organ level disease ensue
  • Telomere length doesn’t matter, but the rate of loss does
  • Typically, leukocyte telomere lengths are measured (because it’s easy) and they are poor representations of telomere lengths in the body
  • Replicative senescence should not be confused with cell aging
  • Telomerase can reset aging in vitro and reset skin age ex vivo as well as other tissues
  • Data suggests we will soon be able to reverse aging in clinical trials
  • It’s difficult to measure telomere lengths of neurons and other brain cells due to the lack of brain biopsies, however it may be possible to measure enzymes and genes in cerebral spinal fluid to get a proxy measurement
  • There is still no good measure of telomere fluctuation over the lifetime
  • People should be focusing on shortest telomere length rather than mean telomere length
  • Fossel doesn’t necessarily care about telomeres, he is interested in clinically effective targets for interventions against aging and telomeres happen to be the best option right now
  • Connective neurons may not divide but nearby glial cells do divide, and neurons are dependent on those cells for their health
  • Cell signaling is important for aging, and DNA is sometimes used as a signaling molecule
  • Good theory is one thing but data wins every time
  • Near term target is to show efficacy in a phase 1 clinical trial

 

Challenge:

 

  • Need a better gene therapy delivery system