Ologies with Alie Ward - Biogerontology (AGING) with Caleb Finch

Episode Date: February 5, 2019

How long can we live? How much of aging is genetics vs. environment? What does oral hygiene have to do with brain health? What causes Alzheimer’s? How do turtles and naked mole rats live so long? Are there any proven strategies for living a longer life? What's up with whiskey and eggs? World-renowned aging expert and biogerontologist Dr. Caleb "Tuck" Finch takes a quick break from his prolific research at USC to answer Alie's sometimes stupid questions about everything from molecules to movies. And she only has like, 3 life-altering epiphanies during the episode.This week's donation was made to CureALZ.orgMore links at www.alieward.com/ologies/biogerontology"I don't have time for bullshit" pen by Cole ImperiBecome a patron of Ologies for as little as a buck a month: www.Patreon.com/ologiesOlogiesMerch.com has hats, shirts, pins, totes!Follow @Ologies on Twitter or InstagramFollow @AlieWard on Twitter or InstagramSound editing by Steven Ray Morris & Jarrett SleeperTheme song by Nick ThorburnSupport the show: http://Patreon.com/ologies

Oh hey, it's your old dad here saving you some pancakes even though you sleep until 11 a.m. when you visit. Allie Ward back with another episode of oligies. So I have been promising you for weeks an episode about aging and marching toward our demise. Molecule by molecule. Here we are, folks. We made it. So this is an interview that is like concentrated laundry detergent.

It's like eating spoonfuls of instant coffee like cereal. It's to the point it's intensely powerful information, minimal buffoonery, aging. Why? How? Let's get into it. First, let's get some business out of the way. I want to thank everyone supporting on patreon.com slash oligies for submitting their questions, making this show possible.

Anyone wearing oligies merch out and about, I hope you find each other and fall in love. Have me officiate your wedding. And thank you to all the folks who have rated and subscribed and left reviews. I read them all. I know that, for example, Glassville Assas, who said that they changed two passwords and signed into four different accounts to leave a review, which was very hilarious and sweet. Also thank you for the review, KateVF, who says, every week I wait with bated breath for the latest episode to drop.

Allie and her guests are so captivating. In one episode, even brought attention to a medical condition I didn't realize I had and may have saved my life. Thanks all that, Ward. Thank you for continuing to live. Let's talk about old age. Okay, so bio gerontology etymology. So bio means life and geron means old man.

So the biology of an old guy, not super inclusive in terms of its roots, but it's a subset of gerontology. It examines the processes of aging. So how does olding happen? Now I came across this ology after recording a coloniology about turtle lifespans back in November and a Wikipedia page whispered, bio gerontology is a thing. Which ushered me to an article about how one particular ologist has been studying this since the 1950s.

And lo and behold, his office was a few miles away from me in LA. What? So I gingerly begged him via email to hang out and I freaked out when I got a reply. Then I navigated to USC with my vintage purse full of microphones and hope and I knocked on his door 12 seconds after our appointed time. And there he stood, a person who is ranked in the top half percent of the most cited scientists in the world, 500 papers with his name on them, decades of research, thousands of students, scores of studies, this dude in the cardigan in the khaki pants standing

before me with a long white beard and an office piled with books. He is the dude. Now, for a visual, just Google image search father time and then add a laser focused expression and a furrowed brow. He's like a human fountain of knowledge on how our youth slips away. So in the death and dying episode, I talked to Colin Perry who makes ballpoint pens inscribed with a motto, I don't have time for bullshit. And I should have given this bio gerontologist one of these pens as a parting gift because

as you will hear, when you are an expert on mortality factors, you don't suffer fools, you don't waste any time. This man does not have time for bullshit and I love him. So let's get right into it. Let's talk about metabolisms, modern life spans, risk factors for losing your memory, thoughts on a possible cause and cure for Alzheimer's, why we age, secrets of centenarians and what a 78 year old professor and globally lauded science hero does to stay so fit and so sharp.

So sit up straight, take some notes for the concentrated crash course on the forward march of molecules with world-renowned bio gerontologist Dr. Caleb Tuck Finch. It's on like Apple's iTunes and anywhere on the internet. So thank you so much for doing this. So let's go into your background a little bit. Can you tell me why you decided to study aging? Well, as an undergraduate, I was looking to work on fields that had not been fully developed in which there would be the chance to work out some of the basic questions.

And one of my professors at Yale, who was a physicist named Carl Woes, coming into biology in 1958, he said, well, why don't you think about aging? Nobody knows anything about the biology of aging, even much less than how embryos develop. And this was 1958, which was just five years after Watson and Crick, and we didn't know what the genetic code was. So that stuck in my mind. And then when I got to graduate school in New York at Rockefeller University, I did my PhD on aging and the first papers on the neurobiology of aging came out of my work there.

So yes, Dr. Caleb Finch attended Yale on a scholarship working in labs to help pay his tuition, and he graduated in 1961 with a degree in biophysics. And then he went on to Rockefeller University to get his PhD in cell biology, studying cellular activities during aging in mammals. And he gave a talk on this subject, and some chebrony afterward came up to him to say, like, don't bother, everyone already knows what they need to know about aging. And that tall drink of hatred was a pathologist, Peyton Rouse, who had recently won a Nobel Prize.

Finch was like, whatever, dude, and went on to become one of the foremost voices in the highly respected field of senescence research, which that's just a fancy word that means the condition or process of deterioration with age. So what part about the aging process fascinates you the most? Is it the effect neurologically or is it the entire body? It's the unknowns that we are still working out basic mechanisms. And we know that as under some genetic influence, if you have the genes of a mouse, you're only going to live two years.

If you have the genes of a human, you might get to 70, 80, or 90. So it's genetic. But then among individuals, the role of genetics seems to be much less, roughly, identical twins, lifespans. You can attribute 20% of their heritability in aging is due to genes that influence aging. So it's really a minority of the individual differences in humans and in other animals can be attributed to inherited genes. So only 20% is attributed to genes, which is terrible news for those of us who like to

deny personal responsibility. So I've been working on many parts of my career on environmental aspects of how individual gene responses to the environment, to diet, influence outcomes of aging. And I'm now, in the last six, seven years, been focusing on air pollution, which shortens lifespan in proportion to the number of particles per cubic meter and also accelerates almost all of the diseases of aging, including the risk of Alzheimer's. Was that inspired at all by living in Los Angeles? Indirectly, because I have had colleagues in the epidemiology group on the Health Science

Campus who were pointing out to me that the rate of arterial aging in Los Angeles scaled in proportion to the density of air particles in your residence, and the arteries that they were studying were the carotids which go to the brain, and so they kept saying to me, Bench, why don't you're interested in the neurobiology of aging? You really got to see if there's a relationship to the arterial aging that we've described as driven by air pollution. So that's what I undertook to study. And last year, we published a definitive paper in collaboration with epidemiologist

JC Chen at the USC School of Medicine, and in that same paper, a mouse model showing that air pollution increases the Alzheimer processes, and we know what molecules are involved in the mouse anyway. And so let's go to the super basics. As someone who is not as well-versed in this as you, what exactly is aging? How do you define aging? Well, the basic way is at a population level that after the age of 40, your risk of mortality essentially doubles every seven or eight years.

So there's an exponential increase in mortality risk, and preceding that is a parallel risk in chronic diseases, heart disease, cancer, and at later ages Alzheimer's. So the individual pathways in this are not understood, but as by age group, aging increases the risk of chronic diseases that are causes of death. And then you can ask at a more fundamental level, what are the mechanisms behind that, and that's where the mystery is. So our risks of disease and dying go exponentially up. Okay, rather than bum you out, let that fact encourage you to write the novel that you've

been intending to, or call in sick, go to Six Flags tomorrow, or wear the shoes you think you should save for fancy occasions, wear them today. We're all getting old, just go for it, champ. Speaking of, how do you ask a genius expert the most basic bitch question ever? You just do it, people. You live in the now. Watch. Is it that our cells don't regenerate as fast?

Is it? That's part of it. Our molecules don't regenerate as fast. And there's some molecules that are as old as we are in our blood vessels and our connected tissue and in our eyes that undergo molecular deterioration. I know they say you're kind of a new person every seven years. Is that? Not at all correct.

Okay. So that's in flim flam to debunk for sure. I mean, it's just not true. That's one of those sort of inherited tales that have no scientific substance. I have no idea where that comes from. I gotta look it up. Yeah, there's no science there. Right.

I didn't think so. It always, I mean, it always, I don't know where that came from, but it's an interesting myth. You know, it's not interesting. It's destructive because it's wrong. Right. By the way, if you're like, was Allie just dying at this point? The answer is yes.

Man, I am dying up here. Both from a molecular standpoint and psychologically, but just stick around because like life, there are twists and there are turns around every corner. PS, where did that destructive myth start? I did a little digging thinking that the origin would be like an ancient tale, but it seems like it started in 2005 with a Swedish stem cell scientist, Jonas Freisen, who had been curious about the ages of different cells in the body and used radioactive carbon-14 tracers, conveniently deposited in humans from nuclear warhead tests in the 60s to

track the age of different cells. So how old are you really? Okay. There's a cool math trick you can do. You take your age and multiply it by 16, then divide it by 16, which is your age. You're just your age. I made you math for nothing. Here's the deal.

Your body is a bunch of different ages, like the lining of your guts, which are just constantly splish-splashing in an acid bath. They're newborns. They turn over every five days or so, but skeletal muscles are 15. They're about to get their learning permits. Some part of your brain are just as old as you are, just about. Other parts turn over faster. The core of your eye lens, you can see ophthalmology episode for more on that, is exactly your

age from pre-birth that never turns over. This is fun. This is like antique roadshow for your meat-covered bone scaffolds. That's what he's ever looked at it that I'm aware of. Well, Ted, did you notice when you showed this to me that I kind of stopped breathing a little bit? Not only that, the condition of this is unbelievable. So in his 900-page book, Longevity, Senescence, and the Genome, Caleb Finch covers the lifespans

and aging processes of everything from apple trees to 40-year-old clams to lobsters who molt away their exeskeleton and avoid some mechanical aging that way, to sturgeon fish that can outlive humans, to relatively old teenage salamanders. So if you listen to the Colonialogy episode, you might remember my aside about the Etruscan shrew that has a heart rate of 1,500 beats per minute and lives two years versus tortoises with slow metabolisms like old Jonathan, a giant tortoise kicking it retirement style on an island at age 187. Graded mole rats can live up to 32 years, perhaps due to an uncanny ability to just

slow down their metabolism when they need to, or repair their wonky DNA, which humans can also do. And I don't think Dr. Finch would enjoy the term wonky, but here we are. Now, how do different animals age? I know you mentioned a mouse might have a lifespan of two years. Each species has its own pattern of aging. So mice don't get Alzheimer's disease and they don't get blood vessel disease and have heart attacks, but they do get cancer and their arteries become more rigid and their

lungs become more rigid because of molecular aging. Those same, that part of aging happens in humans at a much slower rate. And in addition, we have diseases that are special to the human species, including Alzheimer's disease. You've said that other primates don't get Alzheimer's the way that humans do? They have a very much milder aspect of brain aging and there's nothing equivalent in the great apes or in the rhesus monkey to the devastation in the brain of Alzheimer's disease, where there's huge amounts of death of neurons and particular pathways.

But there's major gaps that still remain to be filled before we have a definitive conclusion. But at the present time, I'm comfortable in saying there's nothing that has yet been shown to be equivalent to the level of brain cell damage that happens in Alzheimer's in any other primate. And what is causing that? I know there's many, many factors, but primarily... That's a huge set of unknown questions that the field of Alzheimer's is, and I'm in that field in a significant way, is trying to understand.

So there are changes in the brain that are going on from the age of 30 onwards, and my lab in the 1970s had the first evidence that there's a progressive loss of synapses in the brains of healthy mice and healthy humans in middle age. So there's changes that are happening in the 30s to 40s that are on a pathway that in some individuals takes a more steep dip leading to degeneration of neurons. And we don't know what triggers that steep dip from a more gradual progressive change that everybody experiences. So side note, just about a week or so ago, a study was published that had the internet

all abuzz it had the catchy title. Porphyrymonus gingivalis in Alzheimer's disease brains, evidence for disease causation and treatment with small molecule inhibitors. In short, researchers found that bacteria that caused gingivitis, aka inflamed gums, could lead to brain inflammation leading to Alzheimer's. This seems like huge news, but of course I'm primed for flim flam debunkery. Also I saw there was a study from 2005 by Dr. Margaret Gatz about gum disease and Alzheimer's. So maybe this isn't new news, maybe this is just internet sensationalism.

So I emailed Dr. Finch the other day expecting either crickets or like a pasha, but I got a note right back. He said, just look this up. As a mouse study, it is impressive and supports Margie Gatz prior conclusion that oral infection increases Alzheimer's disease risk, but now gives a mechanism. Exciting. He was on board. This is great.

Even more exciting, he had CC Dr. Margaret Gatz who said, thanks all back. I had a little fangirl moment. So yeah, okay, a tiny bacteria in your gums can make big brain trouble later on and this news is getting us closer to keeping healthier noggins in the future. Is the brain the thing, is the brain the part of our body that ages the quickest or where do we see aging happen first? I'd say blood vessels are. So there's in terms of shared anatomy across men and women, the blood vessels are already

beginning to age even before puberty. Really? So we're already accumulating fat and plaques on our arteries and if you're in a household with smokers as a child, it's accelerated if you're in an area of high air pollution that's accelerated as a child. But then there are differences between men and women by reproductive status and the ovaries of women start to lose egg cells even before birth. Oh wow.

So yeah, you start dying before you're born. Cool, cool, cool, cool. Just cut bangs, texture crush, we're all going to die. So by the time of puberty, half of the egg cells a woman was born with have disappeared and then the rest of them are lost by age 50, which is menopause. There isn't anything equivalent to that in men. Testosterone levels do decline, fertility does decline, but it doesn't have a steep drop off as is the case from women.

And this is an important example of how our embryonic development defines different patterns of aging because the ovary is fully formed in the embryo and those genes turn off and no new egg cells and follicles are formed after birth and that there's nothing like that that happens in the male gonad. Testes, one, two, testes. I just want to acknowledge that the terms men and women and male and female are along a gender binary that doesn't apply to everyone. And Dr. Finch is talking about broad strokes in historical studies and I just want to let

the non-binary folks know out there that I see you and I love you. And what about male versus female lifespans? Have we seen that change over the last few decades or pretty steady? Well, no, they both increased as overall health has increased and it is observed in the health rich populations of the world and our upper income people in this country are health rich people that women are living five years or longer than men. Why is that? We don't know.

I'm trying to think if it's stress or not, but I feel like... It's not simple like that because it's hard to define stress because a completely stress-free life is impossible. In the other hand, there are people who have apparent high levels of stress, women who have eight kids and who live to be 90, so it's not at all clear how we define stress. So, side note, quick shout out to my grandma, Teresa Ward, who lived to be 99 years and nine months despite having 11 children. So what are we doing that is helping progress aging or what are we doing wrong essentially

when it comes to aging? Well, the major health concern across the country is people are eating more energy-rich foods than they need and not getting enough exercise. That's a simple lifestyle take home is boring to say, but if you are even mildly obese in midlife and you're not exercising, you're having a shorter life expectancy. As the fit, Dr. Tuck Finch explained this, I wondered if he ever had a turning point in his life and started to pay more attention to his health, such as I was doing, sitting in his office at that moment.

Has your work changed the way that you live? I would say no. I've always been athletic and physically active and I never smoked and I don't either drink sugary or fat foods, but that's always been my preferred avoidance, so nothing interesting to say. Well, do you play basketball? Do you ski? What's your secret?

No, I used to be a competitive swimmer. I swam in college. I get modest amounts of exercise, not too much to wear my joints out, so I do some hiking, I do some swimming, I do some weightlifting, I mean, nothing exotic or overly strenuous. Not any Zumba or Taibo? No. No kickboxing? No.

Okay. Good. That means I don't have to start that. It's very dull. Nothing unusual. You mentioned something about sugar and I know that inflammatory foods and inflammation is part of your research. How does inflammation affect the human body in terms of aging?

Well, all of the diseases of aging that we worry about, blood vessel disease, obesity, Alzheimer's disease, cancer, involve the molecules of inflammatory responses, so it's deeply built into our systems and in the processes of aging, so that's just a fundamental fact. The term inflammation comes from an ancient understanding of having, when you have a cut, it swells up and it's red and it's hot and it causes pain. Well, the basis for that are the inflammatory cytokines that come in to help the body clean up the damaged tissue, but responses to damaged tissue happen inflammatory responses in arterial disease, in cancer, in obesity, and in Alzheimer's disease, so there's a shared core of inflammatory

proteins that are at work during aging from the day we're born. Flames on the side of my face, breathing, breathing breaths. Is there a way that we should be keeping inflammation at bay? Well, that's part of the idea of exercise and diet which reduces the level of inflammation. Some people are still looking for pills that will do the equivalent of exercise and proper diet, but that's the strongest starting place. So move your bod and eat your greens. We fixed it, America.

And where has the average American lifespan gone? I mean, are we still increasing or have we hit a point? No, we're decreasing in the last 10 years the average lifespan in the United States has decreased and we're now in the 20th or 30th in the world and having in our adult lifespans because of all that we've been talking about. The epidemic of obesity has a direct relationship to that plus the health disadvantages of lower income people who don't see doctors and can't afford medication and then this terrible epidemic of drugs.

Because they're all pushing lifespan down after remarkable gains in the 20th century. And what's happening in other parts of the world and in blue zones where longevity is higher? Side note, what is a blue zone? So this came up in the hematology episode and I only know that because I searched my Google Drive for the word legumes. So a blue zone is a place identified by author Dan Butler who has studied some scientist data and concluded that people in five places live the longest.

Okinawa, Japan, Sudan, Italy, Nekoya, Costa Rica, Akaria, Greece, and a small posse of Seventh Day Adventists in the LA suburb of Loma Linda, California. So what sayeth Dan are commonalities among these groups? Apparently they are prioritizing family above everything else, they smoke less, they eat a lot of veggies, are semi-vegetarian, they have constant, moderate physical activity and good social engagement, which does not mean likes and comments on Instagram but like hanging out with many generations in the community. Oh, also legumes, they eat a lot of legumes.

So does Dr. Finch think this is just a hello beans? I'm not an enthusiastic of something unique about the blue zones. There are peoples in all of the continents who live a little longer than the average but most of my colleagues don't think there's anything unusual about that. But if you look globally, lifespan has been increasing as early life mortality decreased because of reducing infectious disease. But pushing against that is the global epidemic of obesity, the global sale of tobacco, which is huge in Africa and in Asia, and the global issues of air pollution, which is getting

worse in most of the world because of fossil fuel consumption and global warming. And is global warming contributing directly, is a temperature change contributing directly to the way our bodies work or age? That story is emerging. This is a book that I wrote that talks about this, this came out this year. This book is called The Role of Global Air Pollution in Aging and Disease and the title appears in Stark White All Caps Against the Veiled Smoky Silhouette of a Polluted Parisian Skyline.

I am truly confounded as to how one human can be so prolific. I did wonder, I mean you've published over 500 papers and four books. Actually this is my sixth book. How do you approach life, how do you get all of this done, how do you balance all of this personally? Very happy home life, I work very hard but I give myself personal time and avoid feeling ground down. Oh that's very smart, it's a very good life lesson.

What works for me might not work for other people. Don't mind me, I'm just having a moment here, evaluating everything I have done wrong in my life. What do you think as the baby boomer generation starts to age, what do you think the best thing our society can do to? Our society doesn't have much meaning. There is no such thing as our society, right? Who is our society?

There's hundreds of societies, so every community has its own lifestyle. So the main point is healthy diet and exercise and avoid cigarettes and that's totally boring to say but that's really the basis for optimizing outcomes of health at later ages. You need to maintain a healthy lifestyle from childhood onwards. So now is the time when we dive into listener questions and also I mentioned that a portion of the podcast's income goes to a charity each week. This week Dr. Kayla Bench chose CureALZ.org, CureALZ.org, it's a non-profit organization that are dedicated to funding research with the highest probability of preventing, slowing

or reversing Alzheimer's disease. Now to date they have raised over $86 million to fund almost 400 studies and 100% of the funds go directly to research. So thank you listeners for helping a lab buy some pipettes, getting closer to a cure for Alzheimer's. Okay, your listener questions. Now I didn't want to take up too much of the professor's time so I blazed through these questions without reading off a bunch of names but I will insert them when I can.

For example, the first two questions here were asked by Liz Sundin, Athena Ballisteri, Dionne Dabolo, Mike Monakowski, Anonymous Bob, Anna Thompson, Lucille Audenet, which might be Audenet, I'm not sure, and Taylor Munich. I have some listener questions. Almost everyone is just asking what's the secret to aging well? It seems like diet, exercise, rest. Do you think that there's a maximum age that the human body can reach? Well, the evidence is very clear.

Almost nobody gets beyond 100. There's one person in the last 30 years who reached over 120, Jean Calmont. But there are more people getting to 100 but they still, in the last 30 years, she's the only one to get beyond 120. To sign out, Jean Calmont lived to be 122, the oldest human on record, and she was fond of wearing headphones and doing chair gymnastics, prayer, fruit salad, and smoking. Well, one done hill cigarette a day and a small glass of port wine until she was 117, which proves that you're never too old to quit a bad habit and turn over a new leaf.

So seriously, let's nope the smokes, folks, love old dad. Do you think that there's anything to the secrets that they claim, a glass of whiskey a day, a hard boiled egg, stinking singles? I think there's every time someone reaches a remarkable age. I've never heard that said. People say that about them, but I've never heard any of them say that. You have to distinguish between what people say about centenarians and what the centenarians actually say.

So if you talk to New York, Albert Einstein Medical College near Barzilla, he's a great expert on this, but he's shown is that his group of centenarians have the same diseases of other people, and some of them smoked and some of them are still working. There isn't really any genetics or lifestyle that makes it obvious as to how they got there. So super quick. This lab at Albert Einstein Medical College is great and focuses on the metabolic decline of aging. They hypothesize that the brain leads this decline, but, but, but real quick, just let's

get back to if I was hallucinating stories about eggs and whiskey. Okay, good news. My brain still works because the internet is just littered with stories of centenarians with quippy secrets to longevity that are just bogglingly bad advice. So one of the oldest living World War II vets, Richard Overton, who passed away in December, he lived to be 112 and he drank four times as much coffee as me. I get me a couple of coffee sometimes. I drink four cups of coffee in the morning.

This morning I drank about that much whiskey. And four cups of whiskey a day. So okay, he's going to be the only one, right? Nope. Nope. Mariano Pops Rotelli said at 107 that everyone should have a little whiskey nip a day, telling a newspaper quote, I've had a shot of whiskey in my coffee every morning for a hundred years. He said, I went to the doctor three times in a hundred years.

He's dead. I'm still living. Okay. So that's two people. Wait, 105-year-old British man, Jack Reynolds, credits his long life to a daily regimen of whiskey. Agnes Fenton, 111, told reporters that she drank three Miller highlifes and a glass of Johnny Walker daily.

Also at 111, Grace Jones credited a shot of scotch every single day for the past 58 years, which I don't think is how you're supposed to drink scotch, but you live that long, you do what you want. Now did I make up the egg part? I did not. Italian Emma Marano lived to 117. She consumed eggs every day, also a glass of brandy daily, but just put down the bottle, friends.

The current oldest person alive, 160-year-old Kanai Tanaka of Japan credits family, sleep and hope as her secrets for longevity. She also drinks a lot of water. She drinks a lot of water. She's a lot of small fish and soup, and she keeps faith in religious spirits. What I'm saying is, it's anyone's guess, and by anyone, I mean Caleb Finch, and by guess I mean conclusions based on decades of research. You mentioned that genetics is only about 20% of a factor.

Yeah, 20 to 25% somewhere in that. So it's a minority. And what's the role of telomeres in aging? We don't know. So telomeres are the ends of chromosomes that get shortened during cell division. So some of our cells do show shorter telomeres in the immune system. Its actual functional consequence is not clear. So that's clearly, it hasn't been the secret, too.

There's no secret. There's nothing in aging that is a secret. Does he hate me? Again, twists and turns, listen to the end. Also I wanted to take up the least amount of his time, so apologies for not always reading the patron names. You girl here was flustered, but Kelly Meeker, Julie Noble, Sarah Dismet, Kristen Long all had questions about Alzheimer's, which we go back into here.

What's been the most exciting find for you and your work? Well we made a finding that in the realm of Alzheimer's disease that has been important that the most toxic form of the amyloid peptide that people still consider to be one of the major factors in Alzheimer's is small aggregates rather than large amyloid fibrils. So that oligomeric A-beta was discovered in my lab here and it's recognized as the most toxic component in the amyloid cascade. So that was one of our discoveries. And I would say the other discovery that we published this year is that air pollution

increases the production of the amyloid peptide. Really? That's published. And the difference in smaller plaques versus bigger plaques, does that signify that it might be more gradual of an onset? Well people don't think that this plaque sizes the importance because the point is that in the vicinity of the amyloid plaque, which is outside of the cells in the brain substance, the neurons that are nearby are less healthy.

Their projections are more twisted and they have more protein abnormalities. So it's really the total plaque load that is associated in some still mysterious ways with the loss of synapses in the brain. And in the end of the day, all of my colleagues and I are in a uniform agreement that it's the loss of synapses that causes the deterioration in Alzheimer's when neurons can no longer talk to each other across synapses. And that might be impeded by the plaques then? Yeah, the plaques in some way seem to be causing loss of synapses.

So the chemistry, biochemistry and molecular biology, this is immensely complicated and there isn't a single pathway that seems to account for it. So it's the plaques that cause the loss of synapses and the question is how do we arrest the plaques? So they're working on it. Now a few folks such as Caitlin Donald, Rose McAthrin, Shannon Patterson, Doreen Olambushan, Caroline Lewis had this next question. Do you find any particular strategies for keeping your brain sharp or for maintaining

neuroplasticity? Well, I told you all I know, exercise and have an active life. Yeah. Puzzles? Anything like that? No? My science is an endless set of puzzles. I don't have to play games to challenge my brain.

Patron Christopher Yersiewicz asked about diets and Juan Pedro Martinez asked this next question specifically. What about vegetarian veganism diets? Any evidence for those? Well, the main point is whatever you eat, keep your blood lipids and blood sugar low. And there are people on vegetarian diets who live as long as people who eat meat rich diets, but it's harder to keep your blood properties healthy if you're eating a lot of fatty meat and a lot of salt.

Patron Evan Munro said, I intermittently fast partly for weight loss and partly because of the apparent benefits to longevity. How much reliable proof is out there that fasting or strict calorie reduction leads to longer life in humans? And what about fasting and that or caloric restriction? Any evidence that it slows aging or gives the body a break? Well, in humans, there's no evidence that fasting or starvation does more than lower as blood lipids, but there's, in a long-term basis, extreme caloric restriction for most

people is simply not sustainable. Doctors who treat obesity have agreed that you can only go so far with somebody who has been obese to buy diet and exercise or something else that keeps causing them to bounce back. But my colleague, Volter Longo, who's the lab right down the hall, former student of mine, has made some important discoveries that a fasting mimicking diet, really only a couple of days a month, improves blood chemistry. I looked him up and boom, VolterLongo.com has the secrets to life, which apparently are not secrets if you just give him away for free on a webpage.

Seriously check that out. Among the bullet points was, eat mostly vegan plus a little fish, limiting meals with fish to a maximum of two or three times a week. Choose fish, crustacean, mollusks with a high omega-3, omega-6, and vitamin B-12 content like salmon, anchovies, sardines, trout, clams. Pay attention to the quality of the fish, choosing those with low levels of mercury, and confine all eating to within a 12-hour period. For example, start after 8 a.m. and end before 8 p.m.

Don't eat anything within three to four hours of bedtime. There you go. Now, Regarde, there is no mention of Miller High Life or spiking your Folgers with a gas station whiskey or smoking cigars, so just probably don't do that. Anyway, that information was at VolterLongo.com. What is the hardest thing about your job or the part about your job that you dislike the most? Well, there's nothing that I dislike.

I'm happy to say that I'm no longer running large training grants and I'm no longer the director of the Alzheimer's Center, which was another 20 to 30 hours a week on top of everything else I do. I'm 79 and I am enjoying the freedom to not have a large number of people answering to me. I have a group of highly talented, highly motivated people in my research lab and we're doing a lot of good science. What's your favorite part about the field or what you do?

Surprise. Yeah? Yeah. Well, the complexities of biology are just awesome, amazing. Every year there is a new level of mechanisms subcellularly or in how organisms talk to each other. It's just endlessly fascinating. Does this man slow down?

Do you have a seventh book on the way? Yes. There's going to be a popular level book on air pollution in the next year, a year and a half. That's great. Do you drink a lot of caffeine? How do you do all this? I have two cups of coffee a day.

Yeah. Seems to be working. I know. That's all I need. That's all you need. So I'm spending the last two minutes of my time with him just really going for it, y'all. Oh, it's a very stupid question. Did you ever see the movie Benjamin Button and how did you feel about it?

Man, not little children anymore, Benjamin. I did see it. I thought it was clever. Okay. I enjoyed the script writer's imagination and could second guess some of the decisions he made. I saw that five years ago. Yeah.

I was just curious. It seemed like it would be ripe for a lot of mistakes in aging. Well, I mean, you go to the movies to be entertained. Right. You read a novel to be entertained, which means this is not a scientific experience. It was not a documentary from what I recall. No, it was amusing fantasy. Any other things that you're excited about working on or you think people should know

about the aging process or taking care of themselves? Well, I'm collaborating with some anthropologists and a group of people who live in the Bolivian Amazon. What's fascinating about these people, the Simonae, they're living under conditions that of 200 years ago without medication and they're growing their own food and they all have high levels of infection. Some of them get to age 70 or 80, but what's remarkable, a small percent, 10%, nobody lives much over 80, what's remarkable is that their levels of arterial aging are 25 years slower

than in North America and they have almost no heart attacks or strokes. So we're trying to understand what aspects of their environment, their diet and interaction with their genes might slow the arterial aging to such a degree. Do you think there's anything about the gut biome that's at play there? That's an open question. I don't know. We'll see. I guess there's a surprise and a puzzle waiting for you with that.

Thank you so much for letting me ask you so many questions. Thank you so much. Good questions! He said I had good questions, y'all. He does not hate me. So after the interview was over and the mics were off, Dr. Finch said I asked great questions. I was doing a service for science by making the podcast I honestly almost joy wept in my car on the drive home.

He's just super focused and all science on the outside with a very warm and curious heart. I love him. He's great. And he returned my email so fast, I'm a big fan. So to learn more about Dr. Caleb Finch's work, you can go to alleyward.com slash oligies or follow the links in the show notes to my site. I post all kinds of info about his studies and other studies mentioned in the episode. Again, his latest book, Global Air Pollution in Aging, reading smoke signals.

It's even available on Amazon as are many of his other books. Oligies is at oligies on Twitter and Instagram. I'm at alleyward with 1L on both. And thank you, Hannah Lippo and Erin Talbert for moderating the wonderful look of the Oligies podcast Facebook group. Thank you, Oligies transcribers for all the work you're doing to make the back catalog accessible to our deaf and hard of hearing friends. Merch is available at oligiesmerch.com.

Thank you, Shannon Feltas and Bonnie Dutch for helping me manage that. Thanks to new interns, Harry Kim and Caleb Finch. Caleb just started a very fun new podcast called You're Never Too Old about anime and comic books and pop culture. You can check that out. Thank you to assistant editor, Jared Sleeper of the podcast, My Good Bad Brain, for helping with edits and with a little research too. And of course, to editor Ryder Die to at least age 122, Stephen Ray Morris, who puts the

pieces all together. He also hosts the podcast The Percast and See Jurassic Right. Now, if you stick around to the end, you know I tell you a secret. This week's secret is that I have Christmas gifts. I haven't mailed yet. I see them every day. It produces a shame wave. So I got to do that.

I'm sorry, Jennifer and also Sophia and Hannah and Erin. I love you all. I have to go to the post office. So as long as I'm apologizing, I'm sorry to ERICU, RVT of 13 years, who left a four out of five star review because they were PO'd that a turtle episode implied, veterinary medicine was more routine and less dirty than field work. I was so wrong to say that that medicine can be very gross and difficult. And I'm so sorry to have minimized that aspect.

That medicine is dope as hell. I'm so sorry that I made it sound more routine. It was hyperbolic and jocular and I apologize. I hug you and high five you. Also, if you want to say hi or you have a suggestion for improvements to show, maybe before leaving it in a review, just email me at helloallyward at gmail.com. You can also tweet at me or DM me on the grams. I respond to as many as I humanly can.

I read pretty much everything you guys send me, even if I am not able to write you back. I truly love and welcome suggestions on how to make allergies even better. One more secret. I drank Taiwanese cheese tea three times this week. I loved it every time. Okay. Bye-bye. Hackadermatology.

Homiology. Cryptozoology. Litology. Nanotechnology. Meteorology. Lopectology. Nephrology. Seriology.

Celatology. I am old. How old are you? Sixteen. Sixteen. Sixteen. Sixteen. Sixteen.

Sixteen. Sixteen. Sixteen. I am old. Sixteen. Sixteen. Sixteen. Sixteen.

Sixteen. Sixteen. Sixteen. Sixteen. Sixteen. Sixteen. Sixteen. Sixteen.

Sixteen. Marian. Sixteen. Sixteen. Sixteen. thermal.