Rhonda Patrick interviews Dr.Campisi, on Cellular Senescence, Mitochondrial Dysfunction, Cancer & Aging 87,189 views Apr 28, 2017

Judith Campisi, Ph.D. on Cellular Senescence, Mitochondrial Dysfunction, Cancer & Aging 87,189 viewsApr 28, 2017 FoundMyFitness 422K subscribers Dr. Rhonda Patrick interviews Dr. Judy Campisi, a professor of biogerontology at the Buck Institute for Research on Aging, a co-editor in chief of the Aging Journal and an expert on the role of cellular senescence in the aging process and development of cancer. Cellular senescence is so important when we discuss aging and cancer because as our cells accumulate damage, which naturally happens as we age (even as a consequence of the energy generating processes and immune cell activation), there's only so many outcomes that we can expect. The first possibility is that the cells can die. The next is that they can become senescent where they stop dividing but stay alive all-the-while secreting molecules that influence surrounding tissue… or the worst of all possible outcomes, the cells can really go off the rails and become malignant. What's interesting is that, while accumulating senescent cells is inevitable, there are varying strategies of how to tackle senescence and this is of great interest to the field of aging. There are ways to clear out senescent cells with drugs or even dietary and lifestyle interventions. Not only are there ways to kill senescent cells, there are also ways to influence what sort of molecules they produce, possibly limiting the inflammatory ones… even without killing them. In this podcast, Dr. Campisi shares with us many insights on how senescence may be key to our understanding of cancer and aging. Chapters: 00:00:00 - Introduction 00:00:52 - Drivers of aging 00:02:40 - Inflammation 00:08:06 - Senescence 00:18:57 - Lifespan vs healthspan 00:25:20 - Drivers of senescence 00:30:34 - Combating senescence with fasting 00:42:17 - Exercise extends lifespan 00:48:50 - Measuring senescence 00:54:45 - NAD+ boosters 00:56:00 - Fasting mimetics 00:57:00 - Cancer in animals -- Find out more about Judy's work at the Buck Institute for Research on Aging: ▶︎ The Campisi Lab @ Buck: http://www.buckinstitute.org/campisiLab --- Links related to FoundMyFitness: ▶︎ Subscribe on YouTube: http://youtube.com/user/FoundMyFitnes... ▶︎ Join my weekly email newsletter: http://www.foundmyfitness.com/?sendme... ▶︎ Crowdfund more videos: http://www.patreon.com/foundmyfitness ▶︎ Subscribe to the podcast: http://itunes.apple.com/us/podcast/fo... ▶︎ Twitter: http://twitter.com/foundmyfitness ▶︎ Facebook: http://www.facebook.com/foundmyfitness ▶︎ Instagram: http://www.instagram.com/foundmyfitness Chapters Introduction 0:00 Drivers of aging 0:52 Inflammation 2:40 Senescence 8:06 Lifespan vs healthspan 18:57 Drivers of senescence 25:20 143 Comments rongmaw lin Add a comment... FoundMyFitness Pinned by FoundMyFitness FoundMyFitness 5 years ago (edited) In this 1-hour long conversation, we discuss.... • 00:00:52 - The concept of antagonistic pleiotropy, which is an important evolutionary biological explanation for aging whereby a gene may be understood to exhibit more than one trait where at least one of these traits is beneficial to the organism's fitness while yet another trait may be detrimental to that same organism's fitness. • 00:01:32 - What the fundamental molecular processes of aging are and some of the on-going research and general thought is surrounding these processes. • 00:04:05 - The essential differences that a pathologist would observe if they looked at and compared the tissues of a young person with a much older person... even beyond structural differences. • 00:05:00 - The qualities of the two major immune responses and how our innate immune response is both our best friend when it comes to keeping us alive -- but may be our worst enemy when it comes to keeping aging at bay. • 00:05:27 - The infiltration of immune cells into our tissues that occurs as a function of aging and the role of damaged or senescent cells in attracting these immune cells. • 00:07:16 - The changes in gut permeability that happen with age and how that may increase our susceptibility to chronic, low-level inflammation. • 00:08:36 - The evolutionary biology explanation for why we have the mechanism of cellular senescence in the first place. • 00:11:46 - The problem of senescent cells and the characteristics they possess that ultimately drive their ability to further their own accumulation. This is done through a feedback loop whereby the burden of senescent cells itself further increases their accumulation and, thus, associated pathologies. • 00:12:29 - The role of senescent cells in an "epithelial to mesenchymal transition," which facilitate loss of appropriate tissue function and even cancer metastasis and progression. • 00:13:36 - Why diseases of aging, despite occurring in vary diverse tissue types, all begin to crop up simultaneously after 50 or 60 years of life. • 00:16:30 - The clearance of senescent cells as a valid life extension strategy, where some animal research has shown a median lifespan increase by as much as nearly 25% in a mouse model of accelerated aging. • 00:17:50 - Why it might be a bad idea to kill off senescent cells just before surgery or when you might need acute tissue repair. • 00:18:55 - Why tackling cellular senescence may be a strategy that is best employed at strategic intervals rather than every single day. • 00:22:53 - Preservation of brain function and how supporting brain cells called astrocytes seem to be simultaneously the most likely type of brain cells to become senescent and also, perhaps unsurprisingly, to be the ones to give rise to brain cancer. • 00:26:04 - How mitochondrial dysfunction, even in the absence of DNA damage, can cause cells to undergo senescence. • 00:26:34 - The interesting observation that senescence from damage versus energy crisis (failed mitochondria) demonstrates a markedly different and uniquely identifiable phenotype of cellular senescence. • 00:28:41 - The change in immune strategies that occur as a result of aging and how that's reflected by a change in our number of lymphoid versus myeloid lineage cells. • 00:29:09 - Some of the current thought surrounding why we build up senescent cells as we age in spite of the fact that our immune system actually actively plays a role in clearing these cells. • 00:30:40 - The effects of prolonged fasting on the activation of hematopoietic stem cell self-renewal (Dr. Valter Longo's work) and the role this may play in rebalancing lymphoid and myeloid lineage cells. • 00:34:34 - The diverging approaches towards improving healthspan by taking action against senescent cells: use of senolytic drugs (which kill the cells) versus the use of drugs that dampen mTOR, such as rapamycin, which leave the cells alive but ultimately suppress the inflammatory aspects of their secretory phenotype. • 00:35:34 - How periodic prolonged fasts might mimic some of these effects associated with an mTOR dampening drug like rapamycin since fasting is itself a way to temporarily reduce mTOR activity and rodent research suggests it may clear these cells as well. • 00:37:33 - How the secretions of senescent cells can affect the regenerative capabilities of stem cells. • 00:38:14 - Some of the complexities behind scenarios in which cellular senescence may play a positive role in skin health, especially through the secretion of growth factors involved in repair as part of the senescence-associated secretory phenotype (SASP). • 00:41:29 - The open questions regarding the potentially differing origins of senescent cells between various tissue types (e.g. muscles vs. heart) and whether these cells are tied to the type of senescence associated with mitochondrial dysfunction... or... the other phenotype which is more commonly associated with various types of cellular damage. • 00:44:14 - The reason why telomeres are disproportionately the recipients of damage when nuclear DNA damage occurs. • 00:45:26 - The surprisingly large effect of exercise on lifespan that can occur in spite of (sustained) obesity. • 00:47:47 - The benefits of exercise in mitigating some of the side effects of chemotherapy. • 00:48:51 - The practicality of a consumer available clinical assays for DNA damage and the challenge of assessing tissue-specific senescence without the use of invasive biopsy. • 00:54:45 - Some of the interesting studies showing that nicotinamide riboside (a form of Vitamin B3) may improve tissue aging and mitochondrial function and whether this might be associated with reductions in cellular senescence or not. • 00:55:55 - The effect of so-called fasting mimetic compounds (e.g. hydroxycitrate, resveratrol & spermidine) on senescent cells. • 00:57:15 - The interesting capacity for cancer resistance in elephants, possibly conferred, in part, by extra copies of the tumor suppressor gene TP53. • 00:58:11 - The possible existence of cellular senescence as a conserved mechanism in some lower organisms. • 00:59:20 - How some rapidly dividing cells, such as keratinocytes in the basal layer of our skin, tend to undergo senescence more often whereas other rapidly dividing cells, such as those in the gut, tend to undergo programmed cell death as an alternative to senescence. Did you enjoy this podcast? Make sure to consider supporting future episodes for as little or as much as you like by creating a pay-what-you-can subscription here... http://www.foundmyfitness.com/crowdsponsor 82 Ken Elliott Ken Elliott 1 year ago I find Dr. Patrick's work and her push to identify causes of aging so fascinating and interesting I just can't stop watching and learning. And always well-done in terms of clarity and integrity . . . No quasi-truths and unsupported ideas advanced just the facts as we now know. Wonderful! 2 Kieran Doherty Kieran Doherty 5 years ago As a college student going into health science, I show your awesome videos to many of my peers for that extra dose of wonderful information. 40 FoundMyFitness Nils from Alaska Nils from Alaska 3 years ago (edited) Great interview. Re: her comment that it might be best to rid of senescent cells every once in a while, (instead of constantly worrying about it), I've been doing a four to five day fasting mimicking diet once a month to get rid of senescent cells. It's nice to have confirmation that this is likely a helpful thing to do. 2 Iain Campbell Iain Campbell 5 years ago Fascinating as always. Thank you so much for the work on your interview technique also (I know it's tempting to jump in as you often have amazing insights) but this interview where you allowed to her to speak fully was so much easier to watch. Best health show on Youtube! 14 durable1988 durable1988 4 years ago Loved Judith Campisi's insight here! So interesting and she did a great job of conveying highly technical information simply enough for me to grasp. 5 Todd Studer Todd Studer 5 years ago This is one of the best videos that I have ever watched. It would have remained completely engaging had it lasted for many more hours. Thank you so much - I plan to become a sponsor of your show now. 26 antokindness antokindness 5 years ago What a scientific, educating and lovely video! Thank you, dr Rhonda! The best of luck for your pregnancy! 3 Kester Gascoyne Kester Gascoyne 3 years ago Thank you so much Rhonda. You should win a nobel prize or something for distributing this information so readily. Taking your notes word for word. Fred H Fred H 5 years ago So many information packed and inspiring interviews. I wish I worked in this field. 6 FoundMyFitness Anna Beatriz Gebara Anna Beatriz Gebara 4 years ago Great interview, amazing work on both sides! Thank you! 2 gururaj bsavakar gururaj bsavakar 2 years ago Superb! Focused, indepth, informative, Dr R, P style of targeting questions To extract easy explanation for the benefit of all viewers, Top of all admitting , "no one really knows exactly why that is actually happening " ! 1 Robin Aldridge-Sutton Robin Aldridge-Sutton 5 years ago This interview is amazing, keep up the good work! 8 Armand Zaharescu Armand Zaharescu 1 year ago Probably the best podcast i ever watch in 20 years. There are few things (more specific) i learn today but ..there is another way if you understand ancient civilizations (it imply electricity and not chemistry communication of the cells, removing the "good bacteria" from the body, slower cell multiply ). 1MinuteFlipDoc 1MinuteFlipDoc 3 years ago Dr Campisi is just like my third grade teacher. Calm and great explanations. i love her! :) Evan Hodge Evan Hodge 1 year ago Stochastic variation got my attention. These two brilliant people are stunning in every way. More a beautiful dance of ideas than a conversation. Sharing this. Michael Boroski Michael Boroski 2 years ago Such a fan of both of you. Praise and blessings in abundance ✨🙏🏼💗🙏🏾🌱 Magic Productions Magic Productions 5 years ago Highly interesting conversation. Great content as always Rhonda :) 1 Entfaltungsort Entfaltungsort 3 years ago Thanks for your videos on such interesting topics and the way you make them comprehensible for the public! :-) I really enjoy your videos! willow05 willow05 2 years ago This was so fascinating thank you! She is so informative..! 1 WM P WM P 13 days ago Great discussion ladies 🙌 C Burgess C Burgess 2 years ago Super informative, equally interesting, thanks for posting! Chuck Kolb Chuck Kolb 5 years ago So good: deserves another viewing. Scientists keep going even though the popular creed seems belief over science. 1 fgarnold fgarnold 5 years ago fascinating discussion - Dr. Campisi's work is impressive, as are her knowledge & communication skills. a 6 hr interview would have flown by. thanks for choosing her Rhonda - one of your best to date. now I feel obliged to give you some money. :-) 5 Roger Bird Roger Bird 4 years ago I want Rhonda Patrick to be Secretary of Health. 59 strykerking strykerking 5 years ago Thanks for all the content you do, its always very interesting and informative. 11 FoundMyFitness Larissa Ness Larissa Ness 4 years ago Incredible interview. Thank you Dr. Rhonda Patrick!! Sounds like everyone should incorporate a 4 day fast into their lives. How often do you think they should do this? Every year maybe? Baby Baby 4 years ago Good job Rhonda! I have been with you since you began, you are getting better and better.. 1 FoundMyFitness Vivian Parker Vivian Parker 5 years ago So incredible, thank you so much. Dan Volker Dan Volker 5 years ago Very interesting! It had me wondering whether Hyperbaric Oxygen therapy could be effective in regenerating the Senescent cells...Interesting to me, as I am a technical diver, and can easily do dives in 20 to 30 feet of water breathing pure O2....and combine that with my ketogenic diet....If you think there is anything to this, I may start doing this a couple of times each month :-) Closest article I found almost on point with this follows: " Cell cycle synchronization of tumor cells by exposure to hyperbaric oxygenation (HBO) may increase the efficacy of chemotherapy or radiation by placing cells into a chemosensitive portion of the cycle. The purpose of the current study was to examine oxygen pressure-dependent relationships with respect to the cell cycle in prostate tumor cells in vitro. LNCaP cells were grown in an incubator at 21% O2 and then exposed to 100% oxygen at pressures up to 6 atmospheres (atm) for 1.5 h. Cells were then returned to the incubator and evaluated for DNA content by propidium iodide and new DNA synthesis with a pulse-chase experiment. Cell cycle effects were evaluated by flow cytometry. Exposure to HBO increased the percentage of cells synthesizing new DNA in a dose-dependent fashion: 0 atm, 44%; 6 atm, 65%. Cells that synthesize new DNA accumulate in G2/M as a function of partial pressure of oxygen. These results suggest that HBO induces cells to enter the cell cycle and accumulate in G2/M. Cell cycle synchronization and entry of senescent cells into the cell cycle suggest that HBO may be a useful adjuvant to chemotherapy or radiation in the treatment of prostate cancer. There are two potential mechanisms of action that may make HBO efficacious in the treatment of prostate cancer. HBO may potentiate cancer chemotherapeutic agents that cause damage to DNA during DNA synthesis or HBO may inhibit cell division causing accumulation in G2/M." 1 Second Opinion Second Opinion 3 years ago Wow, at 33:00 where she mentions mTOR and rapamycin it's almost as if Dr. Peter Attia presented this word for word in his video 'Peter Attia - Reverse engineered approach to human longevity'. In that video at 40:30 he literally writes out her words "yeast flies worms mice(mammals)" on the chalkboard and goes on to rave about rapamycin. 4 Han Solo Han Solo 3 years ago (edited) makes me sad more and more i get into the matter of reverse aging cancer the more i notice how far away we actually are. Jennie V. Jennie V. 4 years ago you are simply the best. these videos seriously help me survive work some days. makes my brain so happy (: Chris Shermer Chris Shermer 5 months ago Dear DR, which particular strain of Brocoli Seeds do recommed for sprouting. In your POdcast Dr said there are many varieties with very different levels of sulfor aphane and its precursors and precursor enzymes. thank you Elena Benjamin Elena Benjamin 4 days ago Thank you friends for giving yours life to help the humanity! 🤩👍 Irv Paton Irv Paton 4 years ago Best interview ever, in all of history! Ivan B Ivan B 5 years ago There is also a double edged sword with autophagy I saw in some studies. Just something that brought awareness. Augustin Pineda Augustin Pineda 5 years ago You're the Champ Dr. Patrick!!! 13 leon kennedy leon kennedy 3 years ago This convo is the best - love from Irish medical student 1 Sherry Von Sherry Von 3 years ago Just because aging isn't well-understood so far doesn't mean it will remain this way in the immediate future. As long as the current anti-aging experimental treatments such as stem-cell and gene therapy keep working and improving, understanding everything isn't essential. 1 WM P WM P 13 days ago Great discussion ladies 🙌 C Burgess C Burgess 2 years ago Super informative, equally interesting, thanks for posting! Chuck Kolb Chuck Kolb 5 years ago So good: deserves another viewing. Scientists keep going even though the popular creed seems belief over science. 1 fgarnold fgarnold 5 years ago fascinating discussion - Dr. Campisi's work is impressive, as are her knowledge & communication skills. a 6 hr interview would have flown by. thanks for choosing her Rhonda - one of your best to date. now I feel obliged to give you some money. :-) 5 Roger Bird Roger Bird 4 years ago I want Rhonda Patrick to be Secretary of Health. 59 strykerking strykerking 5 years ago Thanks for all the content you do, its always very interesting and informative. 11 FoundMyFitness Larissa Ness Larissa Ness 4 years ago Incredible interview. Thank you Dr. Rhonda Patrick!! Sounds like everyone should incorporate a 4 day fast into their lives. How often do you think they should do this? Every year maybe? Baby Baby 4 years ago Good job Rhonda! I have been with you since you began, you are getting better and better.. 1 FoundMyFitness Vivian Parker Vivian Parker 5 years ago So incredible, thank you so much. Dan Volker Dan Volker 5 years ago Very interesting! It had me wondering whether Hyperbaric Oxygen therapy could be effective in regenerating the Senescent cells...Interesting to me, as I am a technical diver, and can easily do dives in 20 to 30 feet of water breathing pure O2....and combine that with my ketogenic diet....If you think there is anything to this, I may start doing this a couple of times each month :-) Closest article I found almost on point with this follows: " Cell cycle synchronization of tumor cells by exposure to hyperbaric oxygenation (HBO) may increase the efficacy of chemotherapy or radiation by placing cells into a chemosensitive portion of the cycle. The purpose of the current study was to examine oxygen pressure-dependent relationships with respect to the cell cycle in prostate tumor cells in vitro. LNCaP cells were grown in an incubator at 21% O2 and then exposed to 100% oxygen at pressures up to 6 atmospheres (atm) for 1.5 h. Cells were then returned to the incubator and evaluated for DNA content by propidium iodide and new DNA synthesis with a pulse-chase experiment. Cell cycle effects were evaluated by flow cytometry. Exposure to HBO increased the percentage of cells synthesizing new DNA in a dose-dependent fashion: 0 atm, 44%; 6 atm, 65%. Cells that synthesize new DNA accumulate in G2/M as a function of partial pressure of oxygen. These results suggest that HBO induces cells to enter the cell cycle and accumulate in G2/M. Cell cycle synchronization and entry of senescent cells into the cell cycle suggest that HBO may be a useful adjuvant to chemotherapy or radiation in the treatment of prostate cancer. There are two potential mechanisms of action that may make HBO efficacious in the treatment of prostate cancer. HBO may potentiate cancer chemotherapeutic agents that cause damage to DNA during DNA synthesis or HBO may inhibit cell division causing accumulation in G2/M." 1 Second Opinion Second Opinion 3 years ago Wow, at 33:00 where she mentions mTOR and rapamycin it's almost as if Dr. Peter Attia presented this word for word in his video 'Peter Attia - Reverse engineered approach to human longevity'. In that video at 40:30 he literally writes out her words "yeast flies worms mice(mammals)" on the chalkboard and goes on to rave about rapamycin. 4 Han Solo Han Solo 3 years ago (edited) makes me sad more and more i get into the matter of reverse aging cancer the more i notice how far away we actually are. Jennie V. Jennie V. 4 years ago you are simply the best. these videos seriously help me survive work some days. makes my brain so happy (: Chris Shermer Chris Shermer 5 months ago Dear DR, which particular strain of Brocoli Seeds do recommed for sprouting. In your POdcast Dr said there are many varieties with very different levels of sulfor aphane and its precursors and precursor enzymes. thank you Elena Benjamin Elena Benjamin 4 days ago Thank you friends for giving yours life to help the humanity! 🤩👍 Irv Paton Irv Paton 4 years ago Best interview ever, in all of history! Ivan B Ivan B 5 years ago There is also a double edged sword with autophagy I saw in some studies. Just something that brought awareness. Augustin Pineda Augustin Pineda 5 years ago You're the Champ Dr. Patrick!!! 13