Exciting NEW 2nd Generation Senolytics are Coming Soon
Posted: Sat Feb 26, 2022 8:56 pm
2nd generation senolytics are on the way! For example, a recently discovered 2nd generation senolytic called grape seed extract which has been used for years as an anti-inflammatory and antioxidant. Judith Campisi of the Buck Institute co-authored a study recently that found it has incredible senolytic properties and has major improvements over 1st generation senolytics like fisetin.
Advantages of grape seed extract over 1st generation senolytics like fisetin (it's actually a molecule in grape seed extract called procyanidin C1 or PCC1 for short).
- targets multiple types of senescent cells, not just adipose tissue like fisetin
- induces apoptosis in senescent cells while leaving normal cells intact
- grape seed extract has been used as a supplement for years as an antioxidant and anti-inflammatory and is shown to be safe at levels of 300mg/day
- wiped out 90% of senescent cells taken intermittently
- shows life extension in mice of almost 10%
The title of the study is:
"The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice"
https://www.nature.com/articles/s42255-021-00491-8
Lance Hitchings did a video on 2nd gen senolytics recently. Pretty good review of the progress that has been made so far. See link to his video with notes below.
---------------
Lance Hitchings YouTube video on 2nd generation senolytics
https://www.youtube.com/watch?v=Fsu7senvaqk
Parts of his video related to grape seed extract. Notes below:
The goal of this study was to narrow down which substances were best at killing senescent cells without affecting healthy ones. Five substances fulfilled the criteria: fisetin, quercetin, curcumin, piperlongumine, and grapeseed extract. Because the strongest results were recorded for grape seed extract, the researchers decided to focus on that substance.
Grape seed extract is a mixture of a lot of different molecules, so the next step was pinpointing the molecule which had the biggest impact on senescent cells. With the aid of mass spectrometry, researchers identified the main agent: a molecule called procyanidin C1, or PCC1.
In small amounts, PCC1 stopped senescent cells from secreting pro-inflammatory SASP's. In higher concentrations PCC1 can also kill senescent cells, while leaving younger, healthier cells intact.
The next stage was seeing how PCC1 would work in live animals. The scientists treated aged mice with PCC1 once every two weeks for four months. Whenever you clear out senescent cells, their numbers take some time to rebound. Because of this, senolytics should only be used intermittently. That's also a smart way of reducing side effects.
The cohort of mice first treated with PCC1 were two years old or roughly the equivalent of a 70 year old human. The PCC1 therapy increased the lifespan of those aged mice by 9%. They also had lower levels of cellular senescence and were noticably fitter, achieving better results on maximal walking speed, treadmill endurance, and grip strength tests. They then gave PCC1 to even older mice the equivalent of 75 to 90 years old in humans, improving lifespan by 9.4%. PCC1 extended the median lifespan of these mice by 64.2%.
Researchers concluded that PCC1 decreases the risk of age associated mortality, even when given to older individuals. They consider PCC1 to be the key to a new anti-age therapy, which could also help with cancer.
Grape seed extract is a common supplement that has been in use for a long time and is generally considered to be safe. A dosage of 100 to 300mg per day has been used in several scientific studies.
Advantages of grape seed extract over 1st generation senolytics like fisetin (it's actually a molecule in grape seed extract called procyanidin C1 or PCC1 for short).
- targets multiple types of senescent cells, not just adipose tissue like fisetin
- induces apoptosis in senescent cells while leaving normal cells intact
- grape seed extract has been used as a supplement for years as an antioxidant and anti-inflammatory and is shown to be safe at levels of 300mg/day
- wiped out 90% of senescent cells taken intermittently
- shows life extension in mice of almost 10%
The title of the study is:
"The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice"
https://www.nature.com/articles/s42255-021-00491-8
Lance Hitchings did a video on 2nd gen senolytics recently. Pretty good review of the progress that has been made so far. See link to his video with notes below.
---------------
Lance Hitchings YouTube video on 2nd generation senolytics
https://www.youtube.com/watch?v=Fsu7senvaqk
Parts of his video related to grape seed extract. Notes below:
The goal of this study was to narrow down which substances were best at killing senescent cells without affecting healthy ones. Five substances fulfilled the criteria: fisetin, quercetin, curcumin, piperlongumine, and grapeseed extract. Because the strongest results were recorded for grape seed extract, the researchers decided to focus on that substance.
Grape seed extract is a mixture of a lot of different molecules, so the next step was pinpointing the molecule which had the biggest impact on senescent cells. With the aid of mass spectrometry, researchers identified the main agent: a molecule called procyanidin C1, or PCC1.
In small amounts, PCC1 stopped senescent cells from secreting pro-inflammatory SASP's. In higher concentrations PCC1 can also kill senescent cells, while leaving younger, healthier cells intact.
The next stage was seeing how PCC1 would work in live animals. The scientists treated aged mice with PCC1 once every two weeks for four months. Whenever you clear out senescent cells, their numbers take some time to rebound. Because of this, senolytics should only be used intermittently. That's also a smart way of reducing side effects.
The cohort of mice first treated with PCC1 were two years old or roughly the equivalent of a 70 year old human. The PCC1 therapy increased the lifespan of those aged mice by 9%. They also had lower levels of cellular senescence and were noticably fitter, achieving better results on maximal walking speed, treadmill endurance, and grip strength tests. They then gave PCC1 to even older mice the equivalent of 75 to 90 years old in humans, improving lifespan by 9.4%. PCC1 extended the median lifespan of these mice by 64.2%.
Researchers concluded that PCC1 decreases the risk of age associated mortality, even when given to older individuals. They consider PCC1 to be the key to a new anti-age therapy, which could also help with cancer.
Grape seed extract is a common supplement that has been in use for a long time and is generally considered to be safe. A dosage of 100 to 300mg per day has been used in several scientific studies.