Monday, May 17, 2021
Mitochondrial Health

Judith Campisi, Ph.D. on Cellular Senescence, Mitochondrial Dysfunction, Cancer & Aging

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.

Find out more about Judy’s work at the Buck Institute for Research on Aging:

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33 thoughts on “Judith Campisi, Ph.D. on Cellular Senescence, Mitochondrial Dysfunction, Cancer & Aging
  1. 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.

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  2. 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.

  3. I wonder if it is possible that the immine system becomes cytokine resistant over time with years of signaling from an ever increasing number of senescent cells… And in doing so requires more and more pro-inflammatory molecules before it is targeted for death by the immune cells… Thereby increasing systemic inflammation and cancer risks?

  4. In the discussion around mice and people's mortality for unknown reasons, "heart just stopped" makes me think of stem cells. AFAIK that is quite common towards the end of life, the heart cells are not replaced fast enough, or at all. I believe this is where stem cell therapy needs further research. I understand that we can not make stem cells from skin and fat cells. In regards to rapamycin, that may be risky to use for the sole purpose of dampening mTor. There are other molecules that are safer that also target mTor/p53 such as Berberine which I use daily.

  5. You see the design and still believe in evolution !?!? "Cells evolve" because they just thought so !!! Just go to Yahweh and ask to be saved.
    fasting eats senescent cells.

  6. 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 " !

  7. But What if the telomere length is the cause of inflammation? People never seem to think the oter way around. They always go for inflammation, mitochondria etc, but they never consider the idea that telomeres are the reason we get inflammation, mitochondrial dysfunction etc. These things seemed to reverse in mice as well as brain size and cognitive function when they induced telomerase.

  8. I'm already on a NATURAL senolytic product, formulated by a world renowned scientist and biochemist who also formulated a stem cell regeneration product that I took, to support my journey to completely eliminate my Fibromyalgia and MS! He also sits on the board of the world Stem Cell Congress. Feel free to get in touch

  9. Larger things tend to live longer. See also the book WHY BAD THINGS HAPPEN TO GOOD PEOPLE which is about unfair "progeria" disease (rapid aging). Figure out the weight/size thing; figure out the fast-aging. Hit reverse. Live longer. See also Dr Magda Havas research into wifi / microwaves / rf / dirty electricity as causal to rapid aging syndrome. T O X I … C OM

  10. 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 ).

  11. 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!

  12. In terms of longevity America is number 40. Hong-Kong lives the longest period! There is a group of people live in the mountains of China who live off the land and drink the mountain water and they always live to be 125 years old!

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