1 00:00:09,640 --> 00:00:13,159 Speaker 1: Hey, everybody, welcome to another edition of Wisdom Wednesdays, and 2 00:00:13,200 --> 00:00:16,560 Speaker 1: welcome back to the Anti aging series. We are not 3 00:00:16,960 --> 00:00:21,360 Speaker 1: on number nine out of twelve and today we are 4 00:00:21,400 --> 00:00:26,720 Speaker 1: going to talk about cellular sinescence. So sinessnce is linked 5 00:00:26,760 --> 00:00:30,360 Speaker 1: to cell division, and there's very few sales in your 6 00:00:30,400 --> 00:00:33,680 Speaker 1: body that you're actually born with. And what we know 7 00:00:33,760 --> 00:00:39,680 Speaker 1: about ourselves is that they basically they commit suicide process 8 00:00:39,800 --> 00:00:44,480 Speaker 1: called apoptosis, but before they do that, they actually divide. 9 00:00:45,120 --> 00:00:47,080 Speaker 2: And then it turns. 10 00:00:46,720 --> 00:00:50,000 Speaker 1: Out that there is a limit to how often our 11 00:00:50,120 --> 00:00:53,440 Speaker 1: sales can actually divide. And this was first observed by 12 00:00:53,800 --> 00:00:57,720 Speaker 1: a guy called Leonard Hayflick in nineteen sixty five and 13 00:00:57,800 --> 00:01:02,120 Speaker 1: he showed that norman normal sorry human cells have a 14 00:01:02,280 --> 00:01:07,679 Speaker 1: limited capacity to proliferate or divide, and it was called 15 00:01:07,720 --> 00:01:09,000 Speaker 1: the Heyflick limit. 16 00:01:09,480 --> 00:01:11,360 Speaker 2: So this is where your. 17 00:01:11,240 --> 00:01:17,080 Speaker 1: Cells will stop dividing but actually remain metabolically active and 18 00:01:17,120 --> 00:01:20,000 Speaker 1: they kind of become a little bit. 19 00:01:19,959 --> 00:01:21,959 Speaker 2: Like zombie cells. So there's some. 20 00:01:22,360 --> 00:01:25,959 Speaker 1: Characteristics of sinescence cells. So the first is what we 21 00:01:26,040 --> 00:01:29,959 Speaker 1: call cell cycle arrest. This is where the sinescent cell 22 00:01:30,640 --> 00:01:34,240 Speaker 1: exit the sales cycle and they no longer divide, and 23 00:01:34,280 --> 00:01:41,200 Speaker 1: then you have something called sinescence associated secretory phenotype or SASP, 24 00:01:41,920 --> 00:01:46,400 Speaker 1: and that means that they secrete pro inflammatory cider kinds, 25 00:01:46,480 --> 00:01:51,240 Speaker 1: these messenger molecules that basically spread inflammation, and they secreate 26 00:01:51,280 --> 00:01:56,640 Speaker 1: growth factors and things called proteases that actually alter the 27 00:01:56,800 --> 00:02:01,960 Speaker 1: tissue macro environment and have a negative effect on surrounding cells. 28 00:02:02,400 --> 00:02:06,000 Speaker 1: And then there's this resistance to apoptosis that I talked about. 29 00:02:06,080 --> 00:02:10,919 Speaker 1: So that's where the sinescence cells resist program cell death, 30 00:02:11,480 --> 00:02:14,320 Speaker 1: leading to their accumulation over time, and that's when they 31 00:02:14,360 --> 00:02:18,320 Speaker 1: create a bit of molecular mayhem. So if you've ever 32 00:02:18,440 --> 00:02:22,080 Speaker 1: seen Game of Thrones, they're kind of like the White 33 00:02:22,200 --> 00:02:25,320 Speaker 1: Walkers in the body and we really don't want these. 34 00:02:25,760 --> 00:02:29,919 Speaker 1: So what happens, I'm how do we trigger this cellular sinescence. Well, 35 00:02:30,720 --> 00:02:34,160 Speaker 1: I've talked about teleomeres previously. Think of them like the 36 00:02:34,240 --> 00:02:37,480 Speaker 1: little caps on the end of your shoelases. And each 37 00:02:37,560 --> 00:02:41,640 Speaker 1: time the cell divides, that leads to progressive shortening of 38 00:02:41,680 --> 00:02:45,359 Speaker 1: the telomeres, these protective caps at the end of our chromosomes. 39 00:02:45,720 --> 00:02:49,840 Speaker 1: And when those telomeres become critically short, they trigger a 40 00:02:50,000 --> 00:02:53,880 Speaker 1: DNA damage response, which can often lead to sinescence. And 41 00:02:53,919 --> 00:02:58,040 Speaker 1: we talked about telomeres being one of the hallmarks of aging. 42 00:02:58,400 --> 00:03:01,440 Speaker 1: And then we have this DNA damage, so we know 43 00:03:01,600 --> 00:03:07,560 Speaker 1: exposure to things like oxidative stress, radiation, chemotherapy, they can 44 00:03:07,600 --> 00:03:12,040 Speaker 1: all cause DNA damage which can induce senescence. And we 45 00:03:12,080 --> 00:03:16,120 Speaker 1: get oxidive stress from lots of poor lifestyle choices as well. 46 00:03:16,680 --> 00:03:20,520 Speaker 1: And then we have something called oncle gene activation, so 47 00:03:20,560 --> 00:03:23,320 Speaker 1: you probably have heard of oncle genes, and the abnormal 48 00:03:23,360 --> 00:03:28,040 Speaker 1: activation of onco genes can induce senescence as a protective 49 00:03:28,160 --> 00:03:33,880 Speaker 1: mechanism against tumorogenesis or the creation of cancer. So it 50 00:03:33,960 --> 00:03:37,960 Speaker 1: can actually be protective when we're young, this senescence to 51 00:03:38,120 --> 00:03:43,040 Speaker 1: stop these uncle genes forming a big tumor. But as 52 00:03:43,080 --> 00:03:46,680 Speaker 1: we age, senescence and turns into a bad thing. So 53 00:03:46,720 --> 00:03:49,640 Speaker 1: it has this dual role. So as I said, the 54 00:03:49,640 --> 00:03:55,400 Speaker 1: beneficial affects tumor suppression by halting the proliferation of damage celles. 55 00:03:56,040 --> 00:04:00,120 Speaker 1: Senescence acts as a barrier against cancer development. And it's 56 00:04:00,120 --> 00:04:04,840 Speaker 1: also important in wound healing, So sinessin cells can promote 57 00:04:04,840 --> 00:04:09,920 Speaker 1: tissue repair by secreting factors that modulate the immune response 58 00:04:10,440 --> 00:04:14,200 Speaker 1: and facilitate regeneration. So that's the good part of senessen 59 00:04:14,280 --> 00:04:17,320 Speaker 1: So it's a natural process in the body. But the 60 00:04:17,360 --> 00:04:21,400 Speaker 1: detrimental aspects of sinessens are when we age and we 61 00:04:21,480 --> 00:04:26,560 Speaker 1: have this tissue dysfunction, and this accumulation of sinescence cells 62 00:04:26,600 --> 00:04:31,599 Speaker 1: contributes to this tissue dysfunction, chronic inflammation, and progression of 63 00:04:31,640 --> 00:04:36,679 Speaker 1: age related diseases. And then it can when we get older, 64 00:04:36,960 --> 00:04:43,240 Speaker 1: promote tumorogenesis. So these SASP cells I talked about them 65 00:04:43,400 --> 00:04:48,320 Speaker 1: a little bit earlier on those sinescence associated secretory phenotype. 66 00:04:48,800 --> 00:04:50,680 Speaker 2: As we get older, they. 67 00:04:50,560 --> 00:04:55,240 Speaker 1: Can create a pro inflammatory environment that supports the growth of. 68 00:04:55,200 --> 00:04:58,000 Speaker 2: These pre malignant cancer cells. 69 00:04:58,560 --> 00:05:01,039 Speaker 1: So, in summary, sestin can be a good thing when 70 00:05:01,040 --> 00:05:04,200 Speaker 1: we're young. It stops cancer developing, it helps with wound 71 00:05:04,240 --> 00:05:07,239 Speaker 1: healing as well, but as we age it can create 72 00:05:07,279 --> 00:05:11,400 Speaker 1: dysfunction and can then promote the growth of cancer. 73 00:05:11,960 --> 00:05:13,520 Speaker 2: So what do we actually do about it? 74 00:05:13,560 --> 00:05:15,680 Speaker 1: Well, it turns out there are quite a few things 75 00:05:15,720 --> 00:05:18,600 Speaker 1: that we can do to mitigate the impact. 76 00:05:18,200 --> 00:05:19,320 Speaker 2: Of cellular senescence. 77 00:05:20,040 --> 00:05:24,000 Speaker 1: And the first thing no prizes for guessing this is 78 00:05:24,120 --> 00:05:28,480 Speaker 1: regular physical activity and it has been shown to reduce 79 00:05:28,640 --> 00:05:33,719 Speaker 1: markers of cellular senescence and promote healthy aging. One of 80 00:05:33,760 --> 00:05:36,520 Speaker 1: the ways that it does this is by teleomere preservation. 81 00:05:37,160 --> 00:05:41,799 Speaker 1: Regular physical activities associated with longer telomeres, and it actually 82 00:05:41,920 --> 00:05:47,200 Speaker 1: activates the enzyme telomerase, which can actually help to preserve 83 00:05:47,279 --> 00:05:49,720 Speaker 1: our telomeres, and that means. 84 00:05:49,480 --> 00:05:51,600 Speaker 2: That you reduce your cellular aging. 85 00:05:51,960 --> 00:05:55,680 Speaker 1: And then the second way by which exercise is useful 86 00:05:56,080 --> 00:05:59,000 Speaker 1: is reduction of sinescence cells. So it's been shown that 87 00:05:59,160 --> 00:06:05,040 Speaker 1: exercise can decrease the accumulation of sinescence cells, thereby improving 88 00:06:05,120 --> 00:06:10,719 Speaker 1: tissue function. And this can actually be improved by exercising 89 00:06:10,760 --> 00:06:15,160 Speaker 1: in the fasted state increases a tophogy and that clean 90 00:06:15,240 --> 00:06:19,159 Speaker 1: up within muscle sales and it can remove those sinescence cells. 91 00:06:19,440 --> 00:06:22,400 Speaker 1: And there's a study published in Preventative Medicine that found 92 00:06:22,400 --> 00:06:27,360 Speaker 1: that individuals who engage in regular running had longer telomeres 93 00:06:27,680 --> 00:06:32,200 Speaker 1: that equated to approximately nine years of reduced biological aging 94 00:06:32,600 --> 00:06:34,680 Speaker 1: compared to sedentary counterparts. 95 00:06:35,400 --> 00:06:36,840 Speaker 2: So the second way. 96 00:06:36,600 --> 00:06:39,880 Speaker 1: That we can do it is around diet, because diet 97 00:06:40,400 --> 00:06:44,640 Speaker 1: plays a critical role in modulating cellular senescence. And we 98 00:06:44,720 --> 00:06:48,880 Speaker 1: know that calorie restriction either long term calorie restriction. I've 99 00:06:48,880 --> 00:06:51,680 Speaker 1: talked about the pros and cons of that before, or 100 00:06:52,080 --> 00:06:57,160 Speaker 1: intermittent fasting, and that's actually been linked to the delayed 101 00:06:57,160 --> 00:07:00,719 Speaker 1: onset of cellular senescence, and it's been owned in various 102 00:07:00,720 --> 00:07:03,760 Speaker 1: different organisms that it can extend their lifespan, but that 103 00:07:03,920 --> 00:07:05,560 Speaker 1: hasn't been replicated. 104 00:07:05,000 --> 00:07:06,240 Speaker 2: In humans, just to be a war. 105 00:07:06,880 --> 00:07:11,040 Speaker 1: But then eating anti inflammatory foods. We know that foods 106 00:07:11,040 --> 00:07:14,080 Speaker 1: such as amiga three fatty acids are highly anti inflammatory, 107 00:07:14,520 --> 00:07:18,520 Speaker 1: and also foods that are rich in antioxidants and things 108 00:07:18,600 --> 00:07:23,040 Speaker 1: like extra virgin olive oil. They can all mitigate oxidative 109 00:07:23,200 --> 00:07:28,679 Speaker 1: stress and therefore reduce senescence. And there was a study 110 00:07:29,520 --> 00:07:33,360 Speaker 1: that showed that individuals who consumed a diet that was 111 00:07:33,400 --> 00:07:38,680 Speaker 1: anti inflammatory with lots of amiga three fatty acids, fruits, vegetables, 112 00:07:38,760 --> 00:07:41,960 Speaker 1: these sorts of things had reduced risk of chronic diseases 113 00:07:42,000 --> 00:07:46,880 Speaker 1: that were associated with sinescence. Then the third thing is 114 00:07:46,920 --> 00:07:51,000 Speaker 1: around stress management. And so I've talked before about the 115 00:07:51,360 --> 00:07:54,800 Speaker 1: impact of stress at a cellular level, and it's been 116 00:07:54,840 --> 00:07:59,920 Speaker 1: shown that elevated stress levels are associated with accelerated TeleMe 117 00:08:00,160 --> 00:08:04,680 Speaker 1: tell me or sorry shortening, leading to increased cellular senescence 118 00:08:05,280 --> 00:08:11,400 Speaker 1: and inflammation. So stress causes inflammation at a cellular level, 119 00:08:11,760 --> 00:08:16,280 Speaker 1: and that promotes the onset of sinessence in various cell types. 120 00:08:16,640 --> 00:08:22,880 Speaker 1: So making sure that you are using effective stress management techniques, 121 00:08:22,920 --> 00:08:26,600 Speaker 1: trying to avoid things that are highly stressful, and then 122 00:08:26,880 --> 00:08:31,000 Speaker 1: using things like exercise, meditation, and those sorts of things, 123 00:08:31,040 --> 00:08:36,480 Speaker 1: having hobbies, those can actually then slow telling me are 124 00:08:36,520 --> 00:08:39,000 Speaker 1: shortening and reduce hallmarks of aging. And what I mean 125 00:08:39,000 --> 00:08:42,679 Speaker 1: by that is overall stress management techniques have been shown 126 00:08:42,720 --> 00:08:45,000 Speaker 1: to do that. And then the fourth thing you'll not 127 00:08:45,040 --> 00:08:48,960 Speaker 1: be surprised to hear is about quality sleep. Because when 128 00:08:49,000 --> 00:08:55,319 Speaker 1: you're asleep, your DNA repair mechanisms kicking right, and that 129 00:08:55,480 --> 00:08:59,319 Speaker 1: reduces the likelihood of damage induced sinescence. As so, if 130 00:08:59,360 --> 00:09:03,600 Speaker 1: we're having poor sleep, we're not repairing our DNA and 131 00:09:03,640 --> 00:09:07,080 Speaker 1: therefore you're more likely to get senescence. And sleep is 132 00:09:07,080 --> 00:09:12,480 Speaker 1: also important for hormone regulation, things like melatonin and other hormones, 133 00:09:12,720 --> 00:09:17,000 Speaker 1: and melatonin actually has antioxidant properties that actually protects against 134 00:09:17,040 --> 00:09:20,880 Speaker 1: cellular damage. So making sure that we have quality sleep 135 00:09:20,920 --> 00:09:24,400 Speaker 1: because the studies have shown that individuals with poor sleep 136 00:09:24,480 --> 00:09:29,839 Speaker 1: quality or shorter sleep exhibit shorter telomeres and have higher 137 00:09:29,920 --> 00:09:33,920 Speaker 1: levels of cellular senescence markers. Now there's one other thing 138 00:09:35,000 --> 00:09:39,320 Speaker 1: that is emerging at the minute, and that is these 139 00:09:39,480 --> 00:09:44,560 Speaker 1: therapeutics called senalytics. So snalytics are a class of drugs 140 00:09:44,600 --> 00:09:50,480 Speaker 1: and molecules that are designed to selectively eliminate senescence cells 141 00:09:51,520 --> 00:09:56,160 Speaker 1: and therefore mitigating their detrimental effects on the surrounding tissues 142 00:09:56,240 --> 00:09:57,720 Speaker 1: and minimizing aging. 143 00:09:58,280 --> 00:09:58,839 Speaker 2: And there's a. 144 00:09:58,880 --> 00:10:04,120 Speaker 1: Number of and potential senalytic e agents that are actually 145 00:10:04,200 --> 00:10:09,719 Speaker 1: being looked at at the minute. One is cursed curstin 146 00:10:10,120 --> 00:10:12,920 Speaker 1: q u e r c E t i n and 147 00:10:14,160 --> 00:10:18,199 Speaker 1: dasatinib d A s A t I n i B. 148 00:10:18,360 --> 00:10:20,040 Speaker 1: That's a bit of a mouthful to try saying that 149 00:10:20,080 --> 00:10:24,760 Speaker 1: after a few drinks, dacatinib and cursotin. Now that combination 150 00:10:25,400 --> 00:10:29,480 Speaker 1: has actually been shown to clear sinescent cells in pre 151 00:10:29,600 --> 00:10:34,520 Speaker 1: clinical studies and actually improve physical function in aged mice 152 00:10:35,000 --> 00:10:38,560 Speaker 1: and humans, and early human trials suggest that there are 153 00:10:38,720 --> 00:10:45,359 Speaker 1: potential benefits for individuals with things like osteoarthritis and idiopathic 154 00:10:45,440 --> 00:10:46,880 Speaker 1: pulmonary fibrosis. 155 00:10:46,960 --> 00:10:47,160 Speaker 2: Right. 156 00:10:47,760 --> 00:10:53,400 Speaker 1: Then, another molecule called phisotin. This is a flavonoid that's 157 00:10:53,440 --> 00:10:57,439 Speaker 1: found in things like strawberries, apples, onions, and it has 158 00:10:57,440 --> 00:11:01,559 Speaker 1: actually got demonstrated s analytic activity in lots of animal 159 00:11:01,600 --> 00:11:05,559 Speaker 1: studies and improves the health span and reduces markers of sinescence. 160 00:11:06,200 --> 00:11:12,240 Speaker 1: And then there's a drug called navital clax and that 161 00:11:12,720 --> 00:11:15,800 Speaker 1: was originally developed as a cancer drug, but it's actually 162 00:11:15,800 --> 00:11:19,760 Speaker 1: been shown to induce apoptosis or program cell death in 163 00:11:19,800 --> 00:11:23,080 Speaker 1: sinescence cells. But there are a number of side effects 164 00:11:23,080 --> 00:11:26,400 Speaker 1: that actually remain their concerned. So there's actually quite a 165 00:11:26,400 --> 00:11:29,360 Speaker 1: few human trials that are going on right now. I 166 00:11:29,360 --> 00:11:35,760 Speaker 1: wouldn't be dashing out and buying dasatinib and curstin or fystin, 167 00:11:35,920 --> 00:11:38,240 Speaker 1: although I do have my eye on these things. But 168 00:11:38,880 --> 00:11:43,640 Speaker 1: the Male Clinic is actually doing some synolytic trials and 169 00:11:43,840 --> 00:11:50,360 Speaker 1: looking at dacatinib and cursotin in older adults to evaluate 170 00:11:50,679 --> 00:11:54,920 Speaker 1: its effects on physical function and inflammatory markers and chronic diseases. 171 00:11:55,600 --> 00:11:59,960 Speaker 1: And then Unity Biotechnology is actually conducting some clinical trials 172 00:12:00,400 --> 00:12:06,199 Speaker 1: on senalytic drugs for osteoarthritis, age related macular degeneration, and 173 00:12:06,320 --> 00:12:09,720 Speaker 1: neurodegenerative diseases. And then there's there's there's quite a big 174 00:12:09,760 --> 00:12:13,880 Speaker 1: study going on called the Team Study, and that is 175 00:12:14,120 --> 00:12:18,440 Speaker 1: targeting aging with met form and t a m UH 176 00:12:18,840 --> 00:12:21,319 Speaker 1: and a low met form. It is not a senalytic. 177 00:12:22,720 --> 00:12:26,360 Speaker 1: This big study is investigating whether met forming, which is 178 00:12:26,400 --> 00:12:28,720 Speaker 1: an anti diabetic drugs some people may have heard of, 179 00:12:29,200 --> 00:12:32,640 Speaker 1: whether or not it can slow the aging process, and 180 00:12:32,720 --> 00:12:34,920 Speaker 1: one of the things that they're looking at is its 181 00:12:34,960 --> 00:12:39,400 Speaker 1: impact on cellular senescence. So, although I actually think that 182 00:12:39,480 --> 00:12:44,000 Speaker 1: some of these snalytics hold great promise, more research is 183 00:12:44,040 --> 00:12:46,840 Speaker 1: needed before I part with my hard earned cash on 184 00:12:46,960 --> 00:12:49,680 Speaker 1: those and I do want to see the studies showing 185 00:12:49,720 --> 00:12:54,480 Speaker 1: their long term safety and their effectiveness, and then critically, 186 00:12:54,600 --> 00:12:57,240 Speaker 1: what doos do we actually need in humans? 187 00:12:57,240 --> 00:12:59,360 Speaker 2: So I think it's going to be a number of 188 00:12:59,480 --> 00:13:00,800 Speaker 2: years before we know. 189 00:13:00,920 --> 00:13:04,360 Speaker 1: The answers to all those questions. But in summing up, 190 00:13:04,800 --> 00:13:08,560 Speaker 1: cellular sinessence is a double edged sword. It protects against 191 00:13:08,559 --> 00:13:13,800 Speaker 1: cancer and use, but it also contributes to inflammation, tissue dysfunction, 192 00:13:14,320 --> 00:13:17,320 Speaker 1: and aging as those sinescence. 193 00:13:16,720 --> 00:13:18,199 Speaker 2: Sales start to accumulate. 194 00:13:18,640 --> 00:13:23,160 Speaker 1: But fortunately we know that regular exercise and nutrient rich 195 00:13:23,200 --> 00:13:28,240 Speaker 1: anti inflammatory diet, stress management and quality sleep, and potentially 196 00:13:28,640 --> 00:13:32,840 Speaker 1: synolytic therapies can all help to mitigate the negative effects 197 00:13:32,880 --> 00:13:36,920 Speaker 1: of cellular sinessence and promote healthy aging. That's it for 198 00:13:36,960 --> 00:13:38,960 Speaker 1: this week, folks, Catch you next time.