Speaker 1: Hey, everybody, welcome to another edition of Wisdom Wednesdays, and
Speaker 1: welcome back to the Anti aging series. We are not
Speaker 1: on number nine out of twelve and today we are
Speaker 1: going to talk about cellular sinescence. So sinessnce is linked
Speaker 1: to cell division, and there's very few sales in your
Speaker 1: body that you're actually born with. And what we know
Speaker 1: about ourselves is that they basically they commit suicide process
Speaker 1: called apoptosis, but before they do that, they actually divide.
Speaker 2: And then it turns.
Speaker 1: Out that there is a limit to how often our
Speaker 1: sales can actually divide. And this was first observed by
Speaker 1: a guy called Leonard Hayflick in nineteen sixty five and
Speaker 1: he showed that norman normal sorry human cells have a
Speaker 1: limited capacity to proliferate or divide, and it was called
Speaker 1: the Heyflick limit.
Speaker 2: So this is where your.
Speaker 1: Cells will stop dividing but actually remain metabolically active and
Speaker 1: they kind of become a little bit.
Speaker 2: Like zombie cells. So there's some.
Speaker 1: Characteristics of sinescence cells. So the first is what we
Speaker 1: call cell cycle arrest. This is where the sinescent cell
Speaker 1: exit the sales cycle and they no longer divide, and
Speaker 1: then you have something called sinescence associated secretory phenotype or SASP,
Speaker 1: and that means that they secrete pro inflammatory cider kinds,
Speaker 1: these messenger molecules that basically spread inflammation, and they secreate
Speaker 1: growth factors and things called proteases that actually alter the
Speaker 1: tissue macro environment and have a negative effect on surrounding cells.
Speaker 1: And then there's this resistance to apoptosis that I talked about.
Speaker 1: So that's where the sinescence cells resist program cell death,
Speaker 1: leading to their accumulation over time, and that's when they
Speaker 1: create a bit of molecular mayhem. So if you've ever
Speaker 1: seen Game of Thrones, they're kind of like the White
Speaker 1: Walkers in the body and we really don't want these.
Speaker 1: So what happens, I'm how do we trigger this cellular sinescence. Well,
Speaker 1: I've talked about teleomeres previously. Think of them like the
Speaker 1: little caps on the end of your shoelases. And each
Speaker 1: time the cell divides, that leads to progressive shortening of
Speaker 1: the telomeres, these protective caps at the end of our chromosomes.
Speaker 1: And when those telomeres become critically short, they trigger a
Speaker 1: DNA damage response, which can often lead to sinescence. And
Speaker 1: we talked about telomeres being one of the hallmarks of aging.
Speaker 1: And then we have this DNA damage, so we know
Speaker 1: exposure to things like oxidative stress, radiation, chemotherapy, they can
Speaker 1: all cause DNA damage which can induce senescence. And we
Speaker 1: get oxidive stress from lots of poor lifestyle choices as well.
Speaker 1: And then we have something called oncle gene activation, so
Speaker 1: you probably have heard of oncle genes, and the abnormal
Speaker 1: activation of onco genes can induce senescence as a protective
Speaker 1: mechanism against tumorogenesis or the creation of cancer. So it
Speaker 1: can actually be protective when we're young, this senescence to
Speaker 1: stop these uncle genes forming a big tumor. But as
Speaker 1: we age, senescence and turns into a bad thing. So
Speaker 1: it has this dual role. So as I said, the
Speaker 1: beneficial affects tumor suppression by halting the proliferation of damage celles.
Speaker 1: Senescence acts as a barrier against cancer development. And it's
Speaker 1: also important in wound healing, So sinessin cells can promote
Speaker 1: tissue repair by secreting factors that modulate the immune response
Speaker 1: and facilitate regeneration. So that's the good part of senessen
Speaker 1: So it's a natural process in the body. But the
Speaker 1: detrimental aspects of sinessens are when we age and we
Speaker 1: have this tissue dysfunction, and this accumulation of sinescence cells
Speaker 1: contributes to this tissue dysfunction, chronic inflammation, and progression of
Speaker 1: age related diseases. And then it can when we get older,
Speaker 1: promote tumorogenesis. So these SASP cells I talked about them
Speaker 1: a little bit earlier on those sinescence associated secretory phenotype.
Speaker 2: As we get older, they.
Speaker 1: Can create a pro inflammatory environment that supports the growth of.
Speaker 2: These pre malignant cancer cells.
Speaker 1: So, in summary, sestin can be a good thing when
Speaker 1: we're young. It stops cancer developing, it helps with wound
Speaker 1: healing as well, but as we age it can create
Speaker 1: dysfunction and can then promote the growth of cancer.
Speaker 2: So what do we actually do about it?
Speaker 1: Well, it turns out there are quite a few things
Speaker 1: that we can do to mitigate the impact.
Speaker 2: Of cellular senescence.
Speaker 1: And the first thing no prizes for guessing this is
Speaker 1: regular physical activity and it has been shown to reduce
Speaker 1: markers of cellular senescence and promote healthy aging. One of
Speaker 1: the ways that it does this is by teleomere preservation.
Speaker 1: Regular physical activities associated with longer telomeres, and it actually
Speaker 1: activates the enzyme telomerase, which can actually help to preserve
Speaker 1: our telomeres, and that means.
Speaker 2: That you reduce your cellular aging.
Speaker 1: And then the second way by which exercise is useful
Speaker 1: is reduction of sinescence cells. So it's been shown that
Speaker 1: exercise can decrease the accumulation of sinescence cells, thereby improving
Speaker 1: tissue function. And this can actually be improved by exercising
Speaker 1: in the fasted state increases a tophogy and that clean
Speaker 1: up within muscle sales and it can remove those sinescence cells.
Speaker 1: And there's a study published in Preventative Medicine that found
Speaker 1: that individuals who engage in regular running had longer telomeres
Speaker 1: that equated to approximately nine years of reduced biological aging
Speaker 1: compared to sedentary counterparts.
Speaker 2: So the second way.
Speaker 1: That we can do it is around diet, because diet
Speaker 1: plays a critical role in modulating cellular senescence. And we
Speaker 1: know that calorie restriction either long term calorie restriction. I've
Speaker 1: talked about the pros and cons of that before, or
Speaker 1: intermittent fasting, and that's actually been linked to the delayed
Speaker 1: onset of cellular senescence, and it's been owned in various
Speaker 1: different organisms that it can extend their lifespan, but that
Speaker 1: hasn't been replicated.
Speaker 2: In humans, just to be a war.
Speaker 1: But then eating anti inflammatory foods. We know that foods
Speaker 1: such as amiga three fatty acids are highly anti inflammatory,
Speaker 1: and also foods that are rich in antioxidants and things
Speaker 1: like extra virgin olive oil. They can all mitigate oxidative
Speaker 1: stress and therefore reduce senescence. And there was a study
Speaker 1: that showed that individuals who consumed a diet that was
Speaker 1: anti inflammatory with lots of amiga three fatty acids, fruits, vegetables,
Speaker 1: these sorts of things had reduced risk of chronic diseases
Speaker 1: that were associated with sinescence. Then the third thing is
Speaker 1: around stress management. And so I've talked before about the
Speaker 1: impact of stress at a cellular level, and it's been
Speaker 1: shown that elevated stress levels are associated with accelerated TeleMe
Speaker 1: tell me or sorry shortening, leading to increased cellular senescence
Speaker 1: and inflammation. So stress causes inflammation at a cellular level,
Speaker 1: and that promotes the onset of sinessence in various cell types.
Speaker 1: So making sure that you are using effective stress management techniques,
Speaker 1: trying to avoid things that are highly stressful, and then
Speaker 1: using things like exercise, meditation, and those sorts of things,
Speaker 1: having hobbies, those can actually then slow telling me are
Speaker 1: shortening and reduce hallmarks of aging. And what I mean
Speaker 1: by that is overall stress management techniques have been shown
Speaker 1: to do that. And then the fourth thing you'll not
Speaker 1: be surprised to hear is about quality sleep. Because when
Speaker 1: you're asleep, your DNA repair mechanisms kicking right, and that
Speaker 1: reduces the likelihood of damage induced sinescence. As so, if
Speaker 1: we're having poor sleep, we're not repairing our DNA and
Speaker 1: therefore you're more likely to get senescence. And sleep is
Speaker 1: also important for hormone regulation, things like melatonin and other hormones,
Speaker 1: and melatonin actually has antioxidant properties that actually protects against
Speaker 1: cellular damage. So making sure that we have quality sleep
Speaker 1: because the studies have shown that individuals with poor sleep
Speaker 1: quality or shorter sleep exhibit shorter telomeres and have higher
Speaker 1: levels of cellular senescence markers. Now there's one other thing
Speaker 1: that is emerging at the minute, and that is these
Speaker 1: therapeutics called senalytics. So snalytics are a class of drugs
Speaker 1: and molecules that are designed to selectively eliminate senescence cells
Speaker 1: and therefore mitigating their detrimental effects on the surrounding tissues
Speaker 1: and minimizing aging.
Speaker 2: And there's a.
Speaker 1: Number of and potential senalytic e agents that are actually
Speaker 1: being looked at at the minute. One is cursed curstin
Speaker 1: q u e r c E t i n and
Speaker 1: dasatinib d A s A t I n i B.
Speaker 1: That's a bit of a mouthful to try saying that
Speaker 1: after a few drinks, dacatinib and cursotin. Now that combination
Speaker 1: has actually been shown to clear sinescent cells in pre
Speaker 1: clinical studies and actually improve physical function in aged mice
Speaker 1: and humans, and early human trials suggest that there are
Speaker 1: potential benefits for individuals with things like osteoarthritis and idiopathic
Speaker 1: pulmonary fibrosis.
Speaker 2: Right.
Speaker 1: Then, another molecule called phisotin. This is a flavonoid that's
Speaker 1: found in things like strawberries, apples, onions, and it has
Speaker 1: actually got demonstrated s analytic activity in lots of animal
Speaker 1: studies and improves the health span and reduces markers of sinescence.
Speaker 1: And then there's a drug called navital clax and that
Speaker 1: was originally developed as a cancer drug, but it's actually
Speaker 1: been shown to induce apoptosis or program cell death in
Speaker 1: sinescence cells. But there are a number of side effects
Speaker 1: that actually remain their concerned. So there's actually quite a
Speaker 1: few human trials that are going on right now. I
Speaker 1: wouldn't be dashing out and buying dasatinib and curstin or fystin,
Speaker 1: although I do have my eye on these things. But
Speaker 1: the Male Clinic is actually doing some synolytic trials and
Speaker 1: looking at dacatinib and cursotin in older adults to evaluate
Speaker 1: its effects on physical function and inflammatory markers and chronic diseases.
Speaker 1: And then Unity Biotechnology is actually conducting some clinical trials
Speaker 1: on senalytic drugs for osteoarthritis, age related macular degeneration, and
Speaker 1: neurodegenerative diseases. And then there's there's there's quite a big
Speaker 1: study going on called the Team Study, and that is
Speaker 1: targeting aging with met form and t a m UH
Speaker 1: and a low met form. It is not a senalytic.
Speaker 1: This big study is investigating whether met forming, which is
Speaker 1: an anti diabetic drugs some people may have heard of,
Speaker 1: whether or not it can slow the aging process, and
Speaker 1: one of the things that they're looking at is its
Speaker 1: impact on cellular senescence. So, although I actually think that
Speaker 1: some of these snalytics hold great promise, more research is
Speaker 1: needed before I part with my hard earned cash on
Speaker 1: those and I do want to see the studies showing
Speaker 1: their long term safety and their effectiveness, and then critically,
Speaker 1: what doos do we actually need in humans?
Speaker 2: So I think it's going to be a number of
Speaker 2: years before we know.
Speaker 1: The answers to all those questions. But in summing up,
Speaker 1: cellular sinessence is a double edged sword. It protects against
Speaker 1: cancer and use, but it also contributes to inflammation, tissue dysfunction,
Speaker 1: and aging as those sinescence.
Speaker 2: Sales start to accumulate.
Speaker 1: But fortunately we know that regular exercise and nutrient rich
Speaker 1: anti inflammatory diet, stress management and quality sleep, and potentially
Speaker 1: synolytic therapies can all help to mitigate the negative effects
Speaker 1: of cellular sinessence and promote healthy aging. That's it for
Speaker 1: this week, folks, Catch you next time.