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Fascinating stuff, discovered very recently at UCSF and two other places, mostly independently: A protein released by blood platelets, PF4, improves cognition in elderly mice. It declines as we age (in both mice and people). It may be the reason why young blood improves cognition and reduces frailty in aging mice, when blood vessels are conjoined to younger mice. Both Calorie restriction and exercise also increase PF4 levels in the blood (of humans). Read: https://www.sciencenews.org/article/platelet-pf4-aging-brain-longevity -- Saul

https://www.sciencenews.org/article/thymus-puberty-important-adults-cancer

The secret to a longer lifespan? Gene regulation holds a clue May 26, 2022 What accounts for longer lifespan? According to new research from biologists at the University of Rochester, a key piece of the puzzle lies in the mechanisms that regulate gene expression. (Getty Images photo) AddThis Sharing Buttons Share to Facebook Share to TwitterShare to LinkedInShare to More Rochester biologists who study the genetics of lifespan suggest novel targets to combat aging and age-related diseases. Natural selection has produced mammals that age at dramatically different rates. Take, for example, naked mole rats and mice; the former can live up to 41 years, nearly ten times as long as similar-size rodents such as mice. What accounts for longer lifespan? According to new research from biologists at the University of Rochester, a key piece of the puzzle lies in the mechanisms that regulate gene expression. In a paper published in Cell Metabolism, the researchers, including Vera Gorbunova, the Doris Johns Cherry professor of biology and medicine; Andrei Seluanov, professor of biology and medicine; and Jinlong Lu, a postdoctoral research associate in Gorbunova’s lab and the first author of the paper, investigated genes connected to lifespan. Their research uncovered specific characteristics of these genes and revealed that two regulatory systems controlling gene expression—circadian and pluripotency networks—are critical to longevity. The findings have implications both in understanding how longevity evolves and in providing new targets to combat aging and age-related diseases. Comparing longevity genes The researchers compared the gene expression patterns of 26 mammalian species with diverse maximum lifespans, from two years (shrews) to 41 years (naked mole rats). They identified thousands of genes related to a species’ maximum lifespan that were either positively or negatively correlated with longevity. They found that long-lived species tend to have low expression of genes involved in energy metabolism and inflammation; and high expression of genes involved in DNA repair, RNA transport, and organization of cellular skeleton (or microtubules). Previous research by Gorbunova and Seluanov has shown that features such as more efficient DNA repair and a weaker inflammatory response are characteristic of mammals with long lifespans. The opposite was true for short-lived species, which tended to have high expression of genes involved in energy metabolism and inflammation and low expression of genes involved in DNA repair, RNA transport, and microtubule organization. Two pillars of longevity When the researchers analyzed the mechanisms that regulate expression of these genes, they found two major systems at play. The negative lifespan genes—those involved in energy metabolism and inflammation—are controlled by circadian networks. That is, their expression is limited to a particular time of day, which may help limit the overall expression of the genes in long-lived species. In comparing the gene expression patterns of 26 species with diverse lifespans, Rochester biologists Vera Gorbunova and Andrei Seluanov found that the characteristics of the different genes were controlled by circadian or pluripotency networks. (University of Rochester illustration / Julia Joshpe) This means we can exercise at least some control over the negative lifespan genes. “To live longer, we have to maintain healthy sleep schedules and avoid exposure to light at night as it may increase the expression of the negative lifespan genes,” Gorbunova says. On the other hand, positive lifespan genes—those involved in DNA repair, RNA transport, and microtubules—are controlled by what is called the pluripotency network. The pluripotency network is involved in reprogramming somatic cells—any cells that are not reproductive cells—into embryonic cells, which can more readily rejuvenate and regenerate, by repackaging DNA that becomes disorganized as we age. “We discovered that evolution has activated the pluripotency network to achieve longer lifespan,” Gorbunova says. The pluripotency network and its relationship to positive lifespan genes is therefore “an important finding for understanding how longevity evolves,” Seluanov says. “Furthermore, it can pave the way for new antiaging interventions that activate the key positive lifespan genes. We would expect that successful antiaging interventions would include increasing the expression of the positive lifespan genes and decreasing the expression of negative lifespan genes.”

https://www.sciencenews.org/article/lizard-like-tuatara-mitochondrial-genomes-cold-tolerance?utm_source=Editors_Picks&utm_medium=email&utm_campaign=editorspicks013121

Dear ALL, I've just received the letter below, from Dr. Luigi Fontana. It describes his latest book, and includes an attached video. Enjoy, -- Saul Dear Saul, how are you? Hope you are doing well in these difficult times. I am writing to bring to your kind attention a new book, entitled the ‘Path to Longevity’, that summarizes more than 20 years of research, clinical practice and my accumulated knowledge on healthy longevity. Here, a video interview with Sunrise TV that encapsulates some of the key topics: https://youtu.be/bho1IfJqCBw My ultimate dream is that by reading this book people might start to examine their current level of physical and psychological health, and their subconscious expectations for the future. I hope that by becoming more aware of their full potential they will unlock a profoundly felt need for transformation and possibly help the world become a better place. Warmest regards, Luigi PROFESSOR LUIGI FONTANA, MD, PhD, FRACP Professor of Medicine and Nutrition Leonard P Ullmann Chair in Translational Metabolic Health Director, Healthy Longevity Research and Clinical Program Charles Perkins Centre | Sydney Medical School (Central Clinical School) Faculty of Medicine and Health The University of Sydney

Hi. I'm new to this forum. I’ve always wanted to live longer, ever since I was a kid. I'm still pretty young but I recently decided to go on a calorie restricted diet. The thing is that I’m not sure how to do that and I could really use some help. I’ve been relatively skinny most of my life. My BMI is around 19 and has been around that since I was a 15-16. I suffer from Hashimoto’s (autoimmune hypothyroidism) and have recently had to eat relatively little to maintain my weight and look and feel like my normal self. I work out 6-8 hours per week of relatively intense exercise and eat around 1600-1800 calories a day. I try to eat nutritious food. I’m sensitive to fiber so I have to restrict my vegetable intake. Eating more than 20 g of fiber per day makes me very gassy and prevents nutrients from getting absorbed. I try to eat nutritious foods that are low in fiber. The way I understand this diet is that people cut calories to the point where their metabolism slows down and their bodies barely get enough calories to survive. But their diet is rich enough to provide all the necessary nutrients by eating lots of vegetables and fiber. What do I need to do if my metabolism is already crawling. I’m on medication so I’m not currently hypo but my metabolism is very slow compared to the way it was before I had thyroid issues. My thyroid hormones are currently in the normal range but they're very close to hypo (my FT3 is at the low end of the healthy range and my FT4 is not that far above it). Do I need to slow down my metabolism more? Do I need to eat less if my BMI is already relatively low? How can I do this diet if I can’t eat fiber.

I want to create food with 0 calories for me to eat my whole life!

Many of us here are fairly robotic, and eat the same thing day in and day out. Some of us enjoy more diversity and enjoy exploring culinary aspects of foods. Yet for many people browsing this forum, they aren't exactly sure what our meals looks like. Let us share our wonderful food creations with one another! I just enjoyed a delicious lunch. It consisted of the following: Purple sweet potato, chick peas, broccoli, cauliflower, carrots, mushrooms, 1 tsp of olive oil, 1 tbsp of 20-spice mix, garlic, oregano, parsley, cilantro, chili peppers, and 2 oranges for dessert. Ingredients were organic when possible. I also get centenarian status for eating Okinawan sweet potato, right? Calorie total was about 700-800, but I don't watch that closely. I just eat more or less depending on what the scale says each day. Did I mention the food was incredibly delicious? Bon appetit!

I follow Dr. Greger's NutritionFacts.org and today he released a video on higher heart rate risk factors for morbidity. I'm curious to know if any one here practices any lifestyle changes to lower heart rate (exercise/meditation/etc) to improve one's chances of living longer. If so, how low is your resting heart rate? I try to practice daily meditation and I know it helps me lower my heart rate and blood pressure, but I'm still quite average in terms of heart rate, probably around 70bpm. I wonder if lowering my resting heart rate to 50bpm or lower would be a good idea or not. I'd prefer not to do excessive endurance exercise (for time and physical stress reasons) to lower it. I'd love to hear what other people think of the topic!

All, I'm sometimes asked by friends and family who aren't quite as obsessive as I am about health & longevity for a few tips they might be able to adopt that might help them stay healthier longer but without "going overboard" like I do. Today I stumbled across an article that I think fits the bill really well, and that I'll point such people to in the future. It is titled 13 Habits Linked to a Long Life (Backed by Science) and it is from the website AuthorityNutrition.com, which I've never considered much of an authority on nutrition, but this article is quite good so I may have to reconsider... Here is the list: Avoid Overeating Eat Some Nuts Use The Spice Turmeric Eat Plenty of Healthy Plant Foods Exercise and Be Physically Active Don’t Smoke Keep Your Alcohol Intake Moderate Prioritize Your Happiness Avoid Chronic Stress and Anxiety Nurture Your Social Circle Increase Your Conscientiousness Drink Coffee or Tea Develop a Good Sleeping Pattern Each of the 13 is explained in clear, easy to understand language. The article describes the science to back up the recommendations, and has references for people who want to learn more. Finally, it's really brief for those with a short attention span. There are three additional items I can think of that I would add to the list: 14. Don't Sit Too Much (ref) 15. Practice Good Oral Hygiene (discussion, discussion) 16. Ask Your Doctor - Get regular medical checkups and recommended tests after age 50, or earlier if you've got risk factors (discussion) Anyone else have health and longevity "best practices" you would or do suggest to friends/family that aren't included on the list? --Dean

Here is a really interesting article on the short tenure enjoyed by most holders of the title of world's oldest person. Here is a cool graphic from article, showing how old all the recent record holders have been, and how long they've reigned: As you can see, since 2000 the oldest living person (invariably a woman) has been between the age of 114 and 117, and they've held the title for a short time relative to the 9 years that Jeanne Calment was at the top. Despite dramatic increases in recent average lifespan, the age of the oldest person alive has remained pretty stable lately: The average age of the oldest-ever people has increased over the past 40 years from around 112 to around 114. --Dean

Arg.... Forum ate my post. Take 2. ---------- Dean, I have the same results as you, also on the 5th SNP, rs3751812! By the way, there's a much easier way to check status on any SNP than logging into 23andMe. Use SNPTips with FireFox. Yes, we learn a lot about the thin phenotype, but I think the real question is the effect on the possibility of benefitting from CR. CR might be easier for you and me, one might guess. I'd say almost the opposite: being thin is easier, but that's not the goal. Someone with the opposite genetic tendency might go from a BMI of 30 to a BMI of 22 or 21 on CR, benefit tremendously, not look scrawny -- maybe not have really low testosterone, etc. -- whereas we, on CR, go from a BMI of 22 or 23 to 18 or less, and maybe don't get as many CR benefits, and get a lot of the downsides. Maybe. Leanness per se confers some health benefits, according to some studies. But being in "survival mode", as you rightly have called it, might be the real goal. And we might not be able to be in extreme survival mode without being dangerously fat-less. Here's where a citizen science project might be very useful! Zeta