A New Class of Intervention in Mitigating Cellular Senescence

[00:05:29]   Most consensus is that types of senescent cells as well as the detrimental effects caused vary, depending on where they are located in the body.

[00:06:09]   The exact extent and quality of those differences is what is being mapped and studied at the moment at a very high level, under a program which is part of the Human Environmental Circular Atlas program. We map cells in the human body and are focused on senescent cells in the human body.

[00:06:49]   What is this metabolite that has a senolytic effect in humans?

• 25-Hydroxycholesterol (25-HC)
  • is an endogenous metabolite in the cholesterol pathway,
  • its functions in a general sense are not well understood,
  • it seems to participate in multiple different pathways involving inflammation,
  • it is produced naturally,
  • it is a fairly potent substance for killing senescent cells.

[00:08:50]   What happens when a senescent cell is killed with the 25-HC?

• When senescent cells die, they release unique substances into the plasma and urine.
• 1 of those is a biomarker, called 15d-PGJ2 (15-Deoxy-Delta12,14-prostaglandin J2), for the level of senescent cells being killed.
• This is a real game changer with regards to evaluating the efficacy of potential senolytics because you can measure whether or not senescent cells are being killed in the individual with a blood or urine test.

[00:11:49]   A discussion on killing of senescent cells and iron release, ensues.

[00:14:31]   The fundamental definition of a senescent cell is, it is an irreversible halt in cell replication. However, the definition is expanding.

[00:16:51]   There are many pathways for cells to becoming senescent and it is likely insulin participates in some of them.

[00:18:36]   An interesting discussion follows on 25-HC and sun exposure.

[00:22:53]   There are some intriguing, preliminary data suggesting that exercise can remove senescent cells.

[00:23:21]   For more information on the Buck Institute and the Melov Lab (see link below).

[00:31:45]   Trying to improve the efficacy of 25-HC, by using it as a tool compound to try to create better senolytics.

[00:32:45]   25-HC and the effect statin drugs have on it as well as some discussion around cholesterol and lifespan – tune in!

[00:36:14]   Listen to the explanation on the relationship between telomeres and senescent cells.

[00:37:35]   Dr Simon explains how science is a little bit like fashion.

[00:40:12]   Carl tells a riveting story about senescent cells and COVID19 after which Dr Simon gives his view.

[00:48:35]   Carl reiterates how utterly important physical strength and expending energy is.

[00:51:17]   What do you think about NAD+?

• Tremendous amount of work in this area over the last decade.
• The beneficial effects of it are not huge.
• Dr Simon explains why.

[00:54:19]   A debate follows on whether as a rule scientists study sick people or athletes. Dr Simon tells Carl about a program, MoTrPAC (Molecular Transducers of Physical Activity Consortium - see link below), running currently, studying masters athletes and the effects of exercise.

[00:56:00]   Metformin as a senolytic.

• Metformin is the poster child for a potential therapeutic for degenerative changes associated with and how we think about it.
• Metformin itself in multiple animal models and human studies are not that impressive, especially when compared to exercise.
• Metformin is good as a model for paving the way for a potential therapeutic for degenerative changes associated with that.
• A lot of the attraction for Metformin is because of its safety profile and not really for the beneficial effects, particularly in fit individuals.

Melov Lab
www.shrnetwork.biz/melov