HoldsUp

Judith Campisi

Buck Institute for Research on Aging

Judith Campisi, Ph.D., is a professor of biogerontology at the Buck Institute for Research on Aging and a co-editor in chief of the journal Aging. Her research focuses on cellular senescence and its roles in the aging process and cancer development. Her published studies investigate mechanisms such as DNA damage, the senescence-associated secretory phenotype (SASP), senotherapeutic strategies, and the impact of senescent cells across various tissues and age-related conditions.

32 claims checked on air: 4 context 2 overstated 25 supported 1 unverified 2 flagged

What they said on air - supported

2 citing their own research

0:04:09supportedhighJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

The term 'inflammaging' was coined by Italian researcher Claudio Franceschi to describe low-level, sterile, chronic inflammation associated with aging.

"No, this is the term that was coined by Claudio Franceschi in Italy. Yeah, and it really refers to the fact that, well, if a pathologist were to take a liver sample, say from a 15-year-old and a 50-year-old, he or she could probably instantaneously tell you who was young and who was old. One would be just looking at the structure of the tissue, but the other is he or she would look for what we call a low-level, sterile, chronic inflammation" (said at 0:04:09)

The term 'inflamm-aging' (or inflammaging) was introduced by Italian immunologist and gerontologist Claudio Franceschi and colleagues in 2000 to describe the progressive, chronic, low-grade pro-inflammatory state that develops with aging and contributes to age-related pathologies and tissue changes.

0:05:39supportedhighJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Innate immune cells generate reactive molecules including hydrogen peroxide, nitric oxide, and hypochlorite (bleach) to kill pathogens nonspecifically.

"The innate immune system isn't very intelligent. It's designed to kill nonspecifically. So these innate immune cells make hydrogen peroxide, nitric oxide, bleach, you know, exactly." (said at 0:05:39)

The claim is supported by established immunological evidence. Activated innate immune phagocytes (such as neutrophils and macrophages) generate reactive oxygen, nitrogen, and halogen species as part of the oxidative/respiratory burst to eliminate invading pathogens in a broadly non-specific manner. These effector molecules prominently include hydrogen peroxide (H2O2), nitric oxide (NO), and hypochlorous acid (HOCl, the active antimicrobial agent in household bleach, produced via myeloperoxidase).

0:10:20supportedvery lowtheir own paperJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Senescent cells secrete bioactive lipids, specifically prostaglandins and leukotrienes, which modulate inflammation, fibrosis, and tissue repair.

"And they also now, we know very new data from our lab, they secrete um bioactive lipids like prostaglandins and leukotrienes, which are very important for modulating inflammation, fibrosis, but also again tissue repair." (said at 0:10:20)

Preclinical in vitro and animal studies demonstrate that senescent cells secrete bioactive lipid mediators as part of the senescence-associated secretory phenotype (SASP), specifically leukotrienes and prostaglandins. These bioactive eicosanoids play active functional roles in modulating local inflammation, promoting or limiting tissue fibrosis, and participating in wound healing and tissue repair. Because the available evidence is derived from cell culture experiments and animal models, the GRADE certainty is very low.

0:11:10supportedhighJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Mutations in genes that regulate senescence-associated cell growth arrest lead to early cancer-related death in both mice and humans.

"So, there are mouse models now, and even some people with mutations in the genes that regulate that growth arrest. And those people die an early death due to cancer, and the mice die an early death due to cancer." (said at 0:11:10)

Cellular senescence acts as a potent tumor suppression mechanism characterized by permanent cell-cycle and growth arrest. Key regulators of this arrest include tumor suppressor pathways such as p53 and p16INK4a/Rb. In humans, germline mutations compromising these pathways (such as TP53 mutations causing Li-Fraumeni syndrome or CDKN2A mutations) predispose individuals to high rates of early-onset malignancies and premature cancer death. Correspondingly, knockout and transgenic mouse models deficient in these senescence-regulatory genes exhibit impaired senescence arrest and die early from spontaneous cancers.

0:11:32supportedvery lowJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Senescent cells appear at wound sites in the skin and produce growth factors that assist in wound healing.

"So, we've shown for example in the skin, senescent cells appear at the wound, and they produce growth factors that help the wound heal." (said at 0:11:32)

Published experimental research in mouse models demonstrates that senescent fibroblasts and endothelial cells appear transiently at cutaneous wound sites and secrete growth factors, notably platelet-derived growth factor AA (PDGF-AA), which promote myofibroblast differentiation and optimal wound closure. Because the direct experimental evidence is derived from preclinical animal models, the GRADE certainty is very low.

0:12:22supportedmoderateJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Cytokines secreted by senescent cells induce an epithelial-to-mesenchymal transition in neighboring epithelial cells, leading to loss of tissue function.

"So, for example, some of the cytokines that senescent cells produce cause what's called an epithelial to mesenchyme transition... Now, when an epithelial cell becomes more mesenchyme-like, it stops talking to its neighbors. And that means the tissue is going to start losing function. And so, senescent cells can change epithelial behavior so that the tissue doesn't function very well" (said at 0:12:22)

Extensive cell biology and translational literature confirms that factors secreted as part of the senescence-associated secretory phenotype (SASP)—including cytokines such as interleukins—can act on neighboring epithelial cells to trigger an epithelial-to-mesenchymal transition (EMT). During EMT, epithelial cells downregulate cell-cell junctions and adhesion molecules (losing contact and communication with adjacent cells) and adopt mesenchymal characteristics, contributing to loss of normal epithelial tissue architecture, tissue dysfunction, and disease progression such as fibrosis and cancer.

0:15:58supportedvery lowJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Co-injecting premalignant cells with senescent cells into mice converts premalignant cells into full-blown malignancies.

"I think I read you did did some experiments out of your lab where you guys injected these premalignant cells into animals with and without the senescent cells. GUEST1: That's exactly right. And with senescent cells, they converted to full-blown malignancy and, you know, eventually killed the animal." (said at 0:15:58)

The claim accurately reflects findings from published experiments conducted by the speaker's laboratory (Krtolica et al., PNAS 2001). In mouse xenograft experiments, co-injecting premalignant epithelial cells with senescent fibroblasts stimulated tumor formation and malignant progression, whereas co-injecting them with presenescent fibroblasts did not. Because the evidence comes entirely from preclinical cell-culture and animal models, the certainty is graded as very low.

0:19:18supportedvery lowJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Genetic clearance of senescent cells in mice significantly increases median lifespan and improves healthspan without a significant increase in maximum lifespan.

"So, um that was an increase in median lifespan... But not an increase in maximum lifespan... So, the the increase in maximum lifespan was not significant. The increase in median lifespan was significant, and so that's what we call healthspan." (said at 0:19:18)

The speaker's statement accurately describes findings from transgenic mouse studies using the INK-ATTAC system to eliminate p16(Ink4a)-positive senescent cells. In wild-type mice, drug-induced clearance of these senescent cells starting at middle age significantly extended median lifespan in both male and female mice across different genetic backgrounds, attenuated age-related organ dysfunction (healthspan), and delayed tumor development, without producing a significant extension in maximum lifespan (Baker et al., 2016). Because this evidence comes entirely from animal (mouse) models, the certainty for translating these exact lifespan parameters to humans is very low.

0:23:39supportedvery lowtheir own paperJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

When astrocytes become senescent, they become less effective at protecting neurons from neurotoxins such as neurotransmitter toxicity.

"And we even have new evidence that astrocytes, as you know, help protect the neurons from certain types of toxicity like neurotransmitter toxicity. And we can show that when astrocytes become senescent, they become less effective in that protective response." (said at 0:23:39)

Preclinical in vitro research supports the claim. Astrocytes normally clear excess neurotransmitters such as glutamate from the synaptic cleft to prevent excitotoxicity. When primary human astrocytes undergo senescence, the expression of glutamate and potassium transporters is significantly downregulated, leading to impaired glutamate clearance and increased neuronal death in co-culture models. Because this evidence is derived from in vitro and preclinical mechanistic models, certainty is graded as very low.

0:26:41supportedvery lowJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Mitochondrial dysfunction alone, in the absence of DNA damage, induces cellular senescence with a distinct secretory profile from DNA-damage-induced senescence.

"We We recently showed, for example, that uh having bad mitochondria in the absence of DNA damage—so this is just mitochondrial dysfunction, if you will... causes cells to senesce. So they will senesce in response to bad mitochondria. What's interesting is the cells senesce, they stop dividing. They do start secreting molecules, but it's a different complement of secreted molecules." (said at 0:26:41)

Published experimental research demonstrates that mitochondrial dysfunction in proliferating human cells induces cellular senescence—termed mitochondrial dysfunction-associated senescence (MiDAS)—independently of classical DNA-damage-response-driven senescence. The resulting secretory phenotype differs substantially from the canonical DNA-damage-induced senescence-associated secretory phenotype (SASP), notably lacking the interleukin-1 (IL-1)-dependent inflammatory profile. Because the supporting evidence comes from in vitro human cell culture and mouse models, the GRADE certainty is very low.

0:27:10supportedhighJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Senescence caused by DNA damage activates inflammatory cytokines IL-6 and IL-8, whereas mitochondrial-dysfunction-induced senescence does not activate this specific cytokine loop.

"So one of the main distinguishing features is with DNA damage, there's a pathway that increases cytokines like IL-6, IL-8. These are very prominent pro-inflammatory cytokines. That doesn't happen with with bad mitochondria. So that loop is pretty much not activated." (said at 0:27:10)

A foundational study by Wiley et al. (2016) introduced Mitochondrial Dysfunction-Associated Senescence (MiDAS) and demonstrated that while DNA damage-induced senescence triggers a classic senescence-associated secretory phenotype (SASP) featuring robust expression of pro-inflammatory cytokines such as IL-6 and IL-8 (driven by IL-1 signaling and NF-κB activation), senescence induced by mitochondrial dysfunction lacks this IL-1-dependent inflammatory response. In MiDAS, a decreased NAD+/NADH ratio activates AMPK and p53, which prevents the activation of the IL-1/IL-6/IL-8 inflammatory SASP loop while maintaining growth arrest.

0:29:06supportedmoderateJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Senescent cells express ligands on their surface that are recognized by natural killer cells, triggering the innate immune system to clear them.

"So for example, senescent cells express on their surface ligands for natural killer cells. And natural killer cells will then attack those senescent cells and kill them." (said at 0:29:06)

Preclinical and cell biology research demonstrates that senescent cells upregulate activating ligands for natural killer (NK) cells—such as NKG2D ligands including MICA and ULBP2—across multiple senescence triggers (such as replicative, oncogene-induced, and DNA-damage-induced senescence). These surface ligands are recognized by activating receptors on NK cells, directly triggering NK cell-mediated cytotoxicity and targeted elimination of senescent cells.

0:32:04supportedvery lowJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Genotoxic chemotherapies induce cellular senescence in transgenic mice, and eliminating those senescent cells eliminates several side effects of chemotherapy.

"So we've shown very recently using mice, a transgenic mouse model, that some of the so-called genotoxic chemotherapies, this chemotherapies that damage DNA, definitely causes senescence and if we eliminate those senescent cells in our transgenic mouse model, we can eliminate uh several of the side effects, several of the bad side effects of chemotherapy." (said at 0:32:04)

A 2017 study from Judith Campisi's group (Demaria et al.) used a transgenic mouse model (p16-3MR) to show that genotoxic chemotherapeutic agents induce cellular senescence in non-cancerous tissues. When these therapy-induced senescent cells were selectively eliminated genetically or pharmacologically, it mitigated multiple adverse effects of the chemotherapy, including bone marrow suppression, cardiac dysfunction, and loss of physical activity/strength. Because this evidence is derived from animal models, the GRADE certainty is very low.

0:32:54supportedvery lowJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Dampening TOR kinase activity either genetically or with rapamycin extends lifespan in yeast, worms, flies, and mice.

"And what has been shown in yeast and worms and flies and mice is that if you dampen—you you can't get rid of TOR activity, you need it for life, but if you dampen TOR activity either genetically or with the drug rapamycin, which is known to target one arm of the TOR pathway, you can extend lifespan." (said at 0:32:54)

Extensive literature in biogerontology confirms that dampening mechanistic target of rapamycin (mTOR/TOR) signaling—either through genetic downregulation of pathway components or pharmacologically with rapamycin—extends lifespan across standard eukaryotic model organisms, including yeast (Saccharomyces cerevisiae), nematodes (Caenorhabditis elegans), fruit flies (Drosophila melanogaster), and mice (Mus musculus). Because the supporting evidence derives entirely from preclinical animal and cellular model organisms rather than clinical human outcomes, the GRADE certainty is rated as very low.

0:33:20supportedvery lowJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Dampening TOR activity with rapamycin suppresses primarily the inflammatory arm of the senescence-associated secretory phenotype (SASP).

"And what we showed recently is that what rapamycin does or dampening TOR activity does is it also suppresses primarily the inflammatory arm of the secretory phenotype of senescent cells." (said at 0:33:20)

Preclinical evidence in cell culture and mouse models demonstrates that dampening mTOR activity with rapamycin selectively blunts the pro-inflammatory cytokines of the senescence-associated secretory phenotype (SASP). Inhibition of mTOR suppresses the translation of membrane-bound IL1A, which in turn reduces NF-κB activity and downstream inflammatory cytokine secretion (such as IL6). Because the supporting evidence is currently limited to in vitro cellular models and animal experiments, the certainty of the body of evidence is very low for human clinical conclusions.

0:34:32supportedmoderateJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

mTOR-dampening drugs suppress secretion in senescent cells rather than killing them, and the suppression lasts beyond drug application because it breaks a pro-inflammatory feedback loop that takes time to re-establish.

"unlike some of these other drugs that they still so-called senolytic drugs that actually kill senescent cells, the mTOR drugs, the mTOR dampening drugs suppress the ability of senescent cells to secrete. And the effects are uh last longer than the application of the drug in the sense that we know that part of that secretory pro-inflammatory secretory phenotype is due to a feedback loop and what dampening mTOR does is it breaks the loop. And the loop takes time to reestablish." (said at 0:34:32)

mTOR inhibitors (such as rapamycin) function as senomorphics—drugs that suppress the senescence-associated secretory phenotype (SASP) rather than clearing senescent cells directly (senolytics). Research demonstrates that mTOR controls the SASP by selectively promoting the translation of cell-surface interleukin-1 alpha (IL-1A). Reduced membrane-bound IL-1A disrupts an autocrine positive feedback loop that activates NF-κB transcriptional activity, which normally drives the expression and secretion of pro-inflammatory cytokines such as IL-6.

0:36:25supportedvery lowJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Mitochondrial dysfunction associated senescence (MiDAS) is driven by an altered NAD/NADH ratio.

"So that's what we've shown is that this mitochondrial dysfunction induced senescence, we call it mitochondrial dysfunction associated senescence or MiDAS. So we call it the MiDAS phenotype. Um really has to do with this altered NAD/NADH ratio and and that's one of the drivers." (said at 0:36:25)

Preclinical experimental research by Wiley et al. (2016) discovered and defined mitochondrial dysfunction-associated senescence (MiDAS), showing that it is driven by a decrease in the cellular NAD+/NADH ratio. In cell culture and mouse models, mitochondrial dysfunction reduced the NAD+/NADH ratio, leading to AMPK and p53 activation, cell-cycle arrest, and a distinct senescence-associated secretory phenotype (SASP). Restoring the NAD+/NADH ratio by expressing an NADH oxidase (LbNOX) or supplementing with nicotinamide mononucleotide (NMN) prevented both growth arrest and the distinct SASP. Because the supporting evidence comes exclusively from in vitro and animal models, certainty is graded as very low.

0:36:45supportedlowJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Altering the NAD/NADH ratio activates AMP kinase (AMPK), which regulates p53.

"Interestingly, so when you change that ratio, you activate a kinase called AMP kinase. AMP kinase is a major um regulator of p53." (said at 0:36:45)

Published experimental research supports the claim. Specifically, studies investigating mitochondrial dysfunction and cellular senescence demonstrate that altering the cellular NAD+/NADH ratio triggers AMP-activated protein kinase (AMPK) signaling, which subsequently phosphorylates and activates p53 to regulate cellular senescence and growth arrest. Because this describes mechanistic pathway findings primarily established in cell culture and animal models, the certainty is graded as low.

0:38:46supportedvery lowJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Senescent cells secrete factors and growth factors that can promote cell reprogramming and stimulate tissue regeneration in neighboring cells.

"two labs have now shown that um senescent cells can also produce growth factors or factors that help neighboring cells reprogram to stimulate regeneration. And they do it again by their secretory phenotype." (said at 0:38:46)

Preclinical studies from independent research groups have demonstrated that senescent cells release factors via their senescence-associated secretory phenotype (SASP), notably cytokines such as interleukin-6 (IL-6), which act in a paracrine manner to enhance cellular plasticity and promote in vivo reprogramming of neighboring non-senescent cells to facilitate tissue repair and regeneration. Because the supporting evidence derives entirely from animal and cellular models, the certainty of evidence is very low.

0:41:24supportedmoderateJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Mitochondrially induced senescent cells secrete amphiregulin, an EGF-like growth factor.

"They produce some growth factors. Yes. They produce, for example, amphiregulin, which is a EGF-like growth factor." (said at 0:41:24)

Published experimental research demonstrates that mitochondrial dysfunction in proliferating cells triggers a distinct cellular senescence response (mitochondrial dysfunction-associated senescence, or MiDAS). Unlike standard senescence-associated secretory phenotypes (SASP), which are dominated by IL-1-dependent inflammatory cytokines (such as IL-6 and IL-8), the MiDAS secretome is characterized by an altered profile enriched in specific growth factors and signaling molecules, including amphiregulin (AREG), an epidermal growth factor (EGF) family ligand.

0:44:15supportedlowJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Guanine bases in telomeric DNA have high susceptibility to oxidative damage, making telomeres act as sensors for cellular oxidative damage.

"Well, they they're they have um they have a fairly high proportion of the the nucleotide guanine, guanosine, right? And and that that base is is pretty susceptible to oxidative damage. So it becomes like a sensor for for damage." (said at 0:44:15)

The claim is supported by biophysical and cellular research. Telomeric DNA consists of repetitive guanine-rich sequence motifs (TTAGGG in humans), which have a low ionization potential and are particularly susceptible to oxidative base damage such as 8-oxoguanine formation. Because oxidative lesions accumulate preferentially and persist longer in telomeric sequences compared to non-telomeric regions, disruption of telomere integrity triggers DNA damage responses, cellular senescence, or apoptosis, leading researchers to describe telomeres as cellular sensors for oxidative stress.

0:52:10supportedvery lowJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

In genetically identical mice housed in identical environments, senescent cell burden measured via in vivo luciferase luminescence shows increasing stochastic variation with age.

"In our mice, we have transgenic mice in which senescent cells activate a protein, a luciferase, that we can then measure by luminescence in the whole animal. So, we can follow the appearance of senescent cells in living animals by looking at this luminescence signal... Genetically identical animals, sometimes in the same cage, and the error bars get larger and larger and larger. So, that says there is stochastic variation that's not due to genetic differences that causes identical animals to have some with a high burden of senescent cells, some with a low burden of senescent cells." (said at 0:52:10)

The speaker accurately describes the design and behavior of transgenic reporter mouse models (such as the p16-3MR and related p16-luciferase reporter strains developed in the Campisi laboratory and collaborators). In these animals, the p16^INK4a promoter drives the expression of luciferase (and fluorescent/suicide gene markers), enabling the longitudinal tracking of senescent cell accumulation in living mice via bioluminescence. Published studies using these reporter models confirm that bioluminescent signals from senescent cells increase with age, exhibiting notable variance and tissue specificity among genetically uniform animals during natural and accelerated aging. Because the evidence is derived exclusively from preclinical transgenic mouse models, the GRADE certainty is very low.

0:58:35supportedmoderateJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

C. elegans worms lack cellular senescence markers, whereas Drosophila flies show hints of cellular senescence in dividing gut cells.

"some people have looked in C. elegans and they don't seem to find it there, but then C. elegans is unusual in that the only dividing cells in in the worm is is the germ line. But in Drosophila, you know, there is a small fraction of cells that undergo division in the gut. And there is some hints that there may be senescence that occurs in the gut of the fly." (said at 0:58:35)

The speaker's statement accurately reflects biological findings in invertebrate aging models. In Caenorhabditis elegans, adult somatic tissues are strictly post-mitotic (non-dividing), with active cell division limited to the germline, and classical cellular senescence markers associated with proliferating cells are absent in adult soma. Conversely, adult Drosophila midguts contain actively proliferating intestinal stem cells (ISCs), where markers and features of cellular senescence (including stress- and age-induced senescence phenotypes regulated by JNK signaling and cellular damage) have been demonstrated.

0:59:58supportedmoderateJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Cellular senescence occurs in the basal layer of keratinocytes in human skin.

"and we do see senescence in in the basal layer of keratinocytes in in human skin." (said at 0:59:58)

Published studies examining human epidermal tissue and in vitro models confirm that cellular senescence occurs and accumulates in keratinocytes of the basal layer, particularly in aged or photo-exposed skin, as demonstrated by the presence of classical senescence markers (such as p16INK4a and senescence-associated beta-galactosidase) and novel senescent markers (such as RRM2B).

1:00:35supportedhighJudith Campisi, Ph.D. on Cellular Senescence, Mitochondrial

Senescent cells produce high levels of proteases that degrade collagen.

"they're making a lot of proteases that will destroy collagen, yeah." (said at 1:00:35)

Senescent cells develop a senescence-associated secretory phenotype (SASP) that includes high levels of matrix metalloproteinases (MMPs) and other proteases. These proteases directly degrade extracellular matrix components, including collagen, contributing to tissue remodeling and skin aging.

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