Do men have biological clocks? It’s not just women who have to worry about age and fertility, experts say.

Kaitlin Reilly
January 30, 2023

This article is a repost which originally appeared on yahoo!life

Edited for content. The opinions expressed in this article may not reflect the opinions of this site’s editors, staff or members.

Key Points

‧ There is not as much data on male fertility compared to female fertility.

‧ Certain birth risk factors go up as men age.

‧ Increased medication use as men age can contribute to fertility problems.

When it comes to fertility, the focus tends to fall on women and their (loudly ticking) biological clocks. Yet it’s not just women who have to take age into account when considering when to have children. Experts agree that men’s fertility also depends on their age.

According to Dr. Jane L. Frederick, a reproductive endocrinologist, women get most of the attention because they have a finite number of eggs at birth and must contend with changes in egg quantity and quality starting at age 35.

“Women play an obvious role in reproduction, leading us to believe that the topics of fertility, pregnancy and childbirth are women’s issues, void of male involvement after they provided sperm,” she explains. “However, older men over the age of 45 are much more likely to have children than four decades ago, and yet few men recognize their biological clock is ticking as well.”

A 2017 study from Beth Israel Deaconess Medical Center and Harvard Medical School looked into IVF patients and found that while women of age 40 to 42 had the most difficult time conceiving, the chance of a live birth decreased with older men — even those whose parters were younger women. Exactly why that is, however, remains to be researched.

Dr. T. Mike Hsieh, the director of UCSD Men’s Health Center and professor of urology, tells Yahoo Life that although there is “not as much data” on male fertility as for females, it’s clear that “increased paternal age is associated with decline in sperm count, sperm quality, semen volume, testosterone and ability for sexual activity or erectile dysfunction.” While there isn’t a “specific cutoff,” what’s generally accepted as advanced paternal age starts at around 45.

Dr. Paul Turek, a urologist and expert on fertility in men, adds that men in their late 50s and 60s experience a “definite decline” in fertility compared with younger men. The cause of this decline, he says, may not only be a body’s biological clock, but also the fact that certain risk factors go up as men age. As he notes, “a body has to be very healthy to be normally fertile.” He adds that the “quality of the DNA package” is “altered or reduced” as men age.

“That means that when the DNA payload gets delivered to the egg at the time of fertilization, it is broken into single strands, rather than intact, in double strands,” Turek explains. “Eggs try as hard as they can to ‘fix’ the DNA early on after fertilization, but if the load of damage is in excess of the egg’s capacity to repair it, then there will be no pregnancy or possibly a miscarriage — another case, at a biological level, of women cleaning up the messes that men make.”

Frederick also points out that “the risk of developing a medical condition or being exposed to environmental toxins increases with age for men,” which may make them less fertile.

“A history of chronic illness, such as sickle cell disease, chronic kidney failure, liver conditions like cirrhosis or malnutrition may have an effect on sperm production,” she notes. “Men who develop medical problems later in life may be taking medications that can affect sperm function in an adverse way.”

Men’s testosterone levels steadily decline over time, which can also affect their ability to father a child.

“Declining testosterone levels in men may cause a decline in sexual desire, problems with erection and difficulty in achieving ejaculation — all contributing to the couple’s infertility,” Frederick explains. “The level of testosterone does appear to influence the sexual function and desire in a man, and testosterone replacement improves erectile function, but also causes sperm production to go down and lead to infertility.”

Ultimately, however, Frederick notes that this field has a long way to go. “Many unknowns remain with regards to the older male and infertility,” she says. “Further research will give us a better understanding of age and its impact on all areas of male infertility.”

 

 

 

 

 

 

 

What is NAD+ and what are the benefits of NAD supplements and NAD+

NAD+: is this new wonder supplement the secret to looking and feeling younger for longer?

May 23rd 2022 / Ingeborg Van Lotringen

This article is a repost which originally appeared on GET THE GLOSS

Edited for content. The opinions expressed in this article may not reflect the opinions of this site’s editors, staff or members.

Our Takeaways:

· NAD+ (nicotinamide adenine dinucleotide) is a naturally occurring cellular component.

· NAD+ is responsible for cellular repair as well as energy.

· Exercise and fasting can raise levels of NAD+ in the body.

MOVE OVER COLLAGEN THERE’S A NEW SUPPLEMENT WITH A GROWING FAN BASE PROMISING TO HOLD BACK THE YEARS. IS NAD MORE THAN A FAD? WE ASKED DOCTORS TO WEIGH IN 

Vitamin A, collagen powders, CBD… Not a month goes by when we hear about a new ‘wonder’ ingredient that is going to blitz our ailments and hold back the years. The latest contender is NAD+ (pronounced ‘N.A.D. plus’). Already crowding the shelves of health food stores in the US, where preventative medicine and supplements are an even bigger ‘thing’ than here (and a sign of what’s heading our way!), the energy-generating co-enzyme – a compound naturally found in the body – is beginning to make waves in the UK too.

The claim is that it may improve our health and, by extension, our skin, in a myriad of ways, from giving us more energy to reducing cravings to protecting against cell damage, and much more. It’s even touted as the ultimate anti-ageing pill for its ability to keep youthful energy levels topped up, with fans including biohacker Davinia Taylor. “It helps me get rid of brain fog and actually gives me a feeling of confidence. For me, it peps up my mood and changes my mental clarity, making me feel as if I’m 20,” she told us recently.

In the US, where it’s one of the fastest-growing and buzziest supplements, people have long stopped asking what is NAD+?. “They only want to know what the best supplement is,” says molecular biologist and UK supplement entrepreneur Dr Nichola Conlon. So will it prove to be the game-changer everyone’s looking for, putting a spring in our step, making us feel and look younger or even live longer?

The doctors we spoke to were open-minded. Cosmetic physician Dr David Jack, who has his own range of supplements says: “I’ve seen numerous studies in recent years showing benefits of NAD supplementation in modulating inflammation, metabolic decline and cellular and DNA repair,” he says. “Although the evidence is in its early stages, given the low chance of side-effects it may be a very useful supplement for patients either suffering from neurodegenerative conditions or as part of an anti-ageing supplement routine”.

Let’s investigate further…

What is NAD used for?

NAD+ (sometimes called NADH or NAD) stands for nicotinamide adenine dinucleotide, a natural chemical found in every single cell in the body. Think of it like a battery. It plays a major role in generating cellular energy, as well as in the maintenance and repair of our cells, including our DNA. It’s thought to be involved in more than 500 different reactions that keep cells in good health. No biggie, then.

How does NAD+ work to help fight ageing?

If we have high levels of NAD+, it means we have lots of cellular energy – our cells function optimally and we feel more energetic and alert. It also means the body can repair itself quicker, which helps keep our organs, including our skin, in pristine working order. But just like collagen, our levels of NAD+ decline with age. It’s thought they halve every 20 years, from the day we’re born. With age, the body becomes less able to generate it, plus older and naturally more damaged cells use up NAD+ stores at a higher rate. A downward spiral of NAD+ correlates with the onset of many of the complaints associated with ageing including wrinkles, memory loss, heart problems, dementia, Parkinson’s, vision loss, and more. NAD+ decline is seen as one of the nine main hallmarks of ageing, according to Conlon.

How to increase NAD+ levels

You cannot stop the decline of your body’s ability to produce NAD+, but you can slow down the rate at which the body uses it up. Basically, the healthier you are and the less damage your cells sustain from things like disease, stress, unhealthy lifestyle choices and an unhealthy environment, the more NAD+ you have available for keeping your organs in ‘homeostasis’, i.e. strong, healthy and ‘young’ for their age. So: a good old healthy lifestyle with lots of stress management is, as per usual, the best way to keep this important powerhouse ticking over. Conlon adds that research has shown that the well-known positive benefits of exercise and fasting are down to the fact that they ignite the body’s production of NAD+. “They create an energy stress in the body, which responds by increasing NAD+ to switch on cellular maintenance and repair in order to overcome this temporary strain,” she says. “HIIT and resistance training have been found to be the most effective.”

But in the States, and increasingly over here, supplementing NAD+ is thought to be a way of off-setting its natural decline as well. “Multiple studies have demonstrated that NAD+ boosting strategies have benefits at cellular, animal and human level,” says Conlon. One study suggests that one of the ways NAD+ supplementation can do this is by activating the protection and stabilisation of telomeres, which helps prevent cell death and therefore the risk of long-term diseases setting in. Ultimately, says Conlon, “while I would stop short of saying NAD+ boosters help you live longer, it is clear they improve healthspan, which is the proportion of your life you spend in good health.”

But there is a caveat. There have been thousands of papers written on NAD+ supplementation in animals, and about 20 human studies, says Conlon. But at present, there is no conclusive, long-term proof that it can reverse or delay ageing, and it is important to keep in mind that we are talking about a nutritional supplement here, not medication. That doesn’t stop people from leaping on the chance to try it, of course, preferring to take their chances in the pursuit of a longer, healthier life.

NAD+ benefits

With most of the evidence circumstantial, anecdotal, or based on animal studies, below are some of the things that NAD+ supplementation may be good for. It is prescribed in America (and increasingly, here) by functional medicine practitioners and nutritionists to aid in the recovery of these, but again, not as medication.

NAD to improve sports performance

Due to its energy-boosting abilities (many users report an increase in energy, resilience and recovery) and positive impact on muscle function, NAD+ is popular with athletes and sports performance coaches, says Paul Leadon, co-founder of UK supplement company Hinnao Technology. It is also used (in the US at least) to help treat chronic fatigue syndrome. “I know people use it to support mitochondria (the batteries of cells) so it’s good for those with fatigue,” explains nutritional therapist Daniel O’Shaughnessy.

NAD for sleep issues, hangovers and long Covid

In one study, it was shown NAD+ seems to re-set our internal ‘body clock’. So NAD+ supplementation is sometimes used by people who want to treat jet lag and insomnia. And because it fortifies cells’ defence systems, it is used by some as a hangover cure to help protect the liver from the damage alcohol does. As O’Shaughnessy comments: “it’s used in addiction to support the withdrawal from alcohol and some drugs. It’s also being researched for long-Covid support.”

NAD+ and skin ageing

The world of aesthetics and ‘tweakments’ is keeping a beady eye on NAD as well. No wonder, as high levels of cellular energy mean that the body can more effectively prevent and clear up signs of skin ageing such as brown spots and fine lines. “Not only that, but the basic principle of ‘tweakments’ is that a level of controlled damage is inflicted on the skin, which then sets off a repairing, collagen-boosting mechanism in the skin,” says Conlon. “However, if the body is low on cellular energy, it has trouble performing this tissue repair and it won’t generate much additional collagen, leading to disappointing or even negative results. Boosting NAD+ reserves is thought to shore up this collagen supply and can therefore be the essential missing ‘prep’ step in skin rejuvenation procedures.”

NAD and symptoms of menopause

The booming menopause market is also ready to pounce. “We are super interested in the implications for menopause relief, and are chasing scientific data for this,” says Dr Conlon. “Menopause causes a huge increase in cellular ageing in a short space of time, turning off the energy and repair mechanisms that you so desperately need right at this time of life.” She says the company has lots of anecdotal feedback on NAD+ supplementation having a major impact on how women feel when they take it to offset menopausal symptoms.

“NAD+ is good at mopping up DNA damage and oxidative stress,” says O’Shaughnessy. “Supplementing it may also support memory and cognition.” That means it could help with the dreaded ‘brain fog’.

NAD and fatigue

Cosmetic physician Dr Sophie Shotter says that in her experience NAD+ works to treat tiredness, especially hormonally-related fatigue. “I definitely notice the difference when I supplement; for starters, I don’t get that mid-afternoon energy slump.”

NAD and preventing cravings

Apart from the aforementioned protective effect on the liver and delivering much-needed energy when you’ve been burning the candle at both ends NAD+ can, according to Dr Conlon, “help suppress the cravings that plague addicts of all kinds.” The theory is that this is because having enough NAD+ in your system stops the body ‘running on empty’ from substance abuse. As a result, it craves fewer ‘fresh hits’ of more stimulants.

Biohacker and author Davinia Taylor, a recovering alcoholic, recently told us that she noticed that effect after having a NAD+ IV drip. “It gets rid of any cravings. Think sugar, shopping…. I didn’t even fancy the chips I was trying to treat myself with,” she said. “It shuts down the body’s addictive mechanism and its need for a dopamine rush. It makes me feel not high, not buzzy, not wired like you would from Red Bull – but chipper. It’s like an alternative to hair of the dog that’s actually good for you, and an antidote to the fact that hangovers get worse with age. It’s an awake, clean energy that helps you deal with any stress better; that’s one of the things we get worse at as we get older, and when our hormones are on their way out. This is the ultimate energy shortcut that works for me.”

NAD supplements: what is the best way to take NAD+?

NAD IV drips

Taylor gets her drips from GP Dr Enayat of London biohacking health clinic Hum2n, who offers a ‘substance detox programme’ of five IV drips in one week, starting at £2795, and a three-drip anti-ageing protocol from £1295.
Beware, though: apart from the substantial financial investment, having these drips is also an investment in time, as they typically take three hours to infuse. Unless you take the ‘speedy’ half-hour option which, according to people we’ve spoken to has an unpleasant side effect of feeling temporary stomach and brain pressure as the active works its way into your system.

The payoff, says Leadon, who’s had NAD+ IV drips himself, is a sustained high and clarity of mind. “Drips are great to prepare for a major event or to aid recovery,” he says. “But my preference is always to supplement in a way that’s as close as possible to what the body does naturally. So a little-and-regular approach in the shape of daily oral supplementation is, in my opinion, the best way forward for sustained overall age prevention and support.” He considers the liposomal NAD+ supplement he’s about to launch, will be the next best thing (of course) to an IV drip.

NAD+ liposomal drops

Getting NAD+ into your cells is tricky. “NAD+ is a very large molecule that cannot just penetrate the skin or the mucus membranes in the mouth [ie taken under the tongue] to enter the bloodstream,” says Leadon. “And taken as a capsule, it won’t survive the gut intact.” To get around the issue, Leadon has created a nano-sized version of NAD+ and stabilised it in a ‘liposomal’ delivery system (protected in microscopic lipid bubbles). It’s been shown to go straight into the bloodstream when you place some drops of it under the tongue. “NAD+ is also very sensitive to heat damage so the drops may have to be kept in the fridge,” he says. Currently, the company is in the process of doing third party testing to back up its claims.

Supplements that help the body make NAD+

According to Conlon, getting NAD+ into the bloodstream doesn’t mean it actually gets into the body’s cells. “Right now, there’s very little proof that it can, apart from some indication that it can permeate some neuronal [brain and nervous system] cells. The exact same, by the way, goes for NAD+ IV drips,” she says.

This is why most NAD+ supplements provide not NAD+, but NAD+ precursors (since you ask – nicotinamide riboside or niagen tryptophan, or nicotinamide mononucleotide – NMN). Unlike the whole NAD+ molecule, these are readily absorbed into the system, and the body then converts them into NAD+.

But as far as Conlon is concerned, this is not enough. “Every cell in your body is like a small factory that needs power to function,” she says. “But with age, these ‘cell factories’ sustain major damage, which means the fuel you supply them with leaches away.” For her, it means that a good NAD+ supplement needs to provide a blend of nutrients that help repair and maintain your cells, alongside the fuel for making NAD+. Her Nuchido Time+ supplement is an example of this and has just been subjected to a double-blind, placebo-controlled crossover study to prove its claims. “We’ve tested the blood of human volunteers and we’ve seen an increase in NAD+ of 242 per cent in 16 days, on the basis of taking six capsules a day,” she says.

Can you take NAD when pregnant?

NAD+ is vital for normal organ development in babies but the advice is to, out of caution, hold off on taking NAD+ supplements in pregnancy. An Australian 2020 study on animals concluded that supplementing with precursor NMN improved the quality of ovarian cells in adult mammals but it’s not known what effect it had on their unborn young.

Are there any side effects of taking NAD+?

From the research so far (which has been done mostly on animals, with a few human studies), very few contra-indications have been flagged for taking supplements with NAD+ precursors, they seem to be very safe ingredients. In the human studies, 1000-2000mg of nicotinamide riboside (one popular precursor) a day had no harmful effects – and most supplements contain 250-300mg a day. However long-term effects in humans are still relatively unknown.

The verdict: is NAD+ the next big thing?

She would say so of course, but Conlon believes it is. “Whether it was Covid that inspired it or not, consumers in the UK have really embraced the idea of long-term preventative healthcare much more than they did before, and they’re looking for solutions that really hold water,” she says. “We’ve seen the popularity of collagen supplements, but the proof is dicey and few people are prepared to take the amount of collagen supplementation required to really see a difference.”

“While the research is growing, the possibilities are far-reaching because cellular energy is at the heart of longevity,” says Dr Conlon. For her, NAD+ supplementation is a way to stay mentally sharp and physically active for as long as possible throughout what are set to be longer lives than ever before.

Dr Sophie Shotter believes in NAD+ supplementation as well: “ I do recommend NAD supplements to patients, often those struggling with hormone-related energy levels,” she says. “But it’s important to note that we cannot supplement NAD directly,” she says. “I opt for NAD+ precursors, but I believe it’s also important to support our cellular ability to produce NAD+ as it decreases with age.”

Dr Shotter supplements patients as well as herself through IV drips with NADH “not a precursor but the ‘reduced’ version of NAD+; it easily converts into NAD+” she explains. She’s also a fan of the Nuchido Time+ supplement. “The fact that it has additional ingredients designed to boost both the cells’ ability to produce as well as recycle NAD+ is a real bonus,” she says. “With consistent use, I believe [supplements] can be very beneficial.”

But despite his strong interest in biohacking, this is one hack that nutritional therapist O’Shaughnessy isn’t getting behind just yet. He feels it’s expensive and certainly not a magic bullet. “NAD+ therapy should just be used as a tool,” he says. “If you’re suffering from fatigue, then it’s vital you consider the functional elements. These include being over-stressed, tackling vitamin and mineral deficiencies (particular in vegan diets which are often lacking iron, vitamin B12 and protein), digestive imbalances, sleep hygiene, food sensitivities, toxin overload, and more.” Taking NAD+ supplements, he says “will be a drop in the ocean if there are all sorts of imbalances in the body. The priority should be on addressing these.”

If you want to invest in an energy supplement, “a vitamin B complex is a cheap all-rounder,” he says. “Common sense says that we should function with optimal energy without the need for NAD+.” Try Healthspan High Strength Vitamin B Complex, £8.99.

Will studies prove him right or wrong? IS NAD+ a fad or the key to helping us age better? We’ll have to wait and see.

 

 

 

David Sinclair: Extending the Human Lifespan Beyond 100 Years | Lex Fridman Podcast

David Sinclair is a geneticist at Harvard and author of Lifespan.

This Podcast is a repost which originally appeared on lexfridman.com
Podcast notes are a repost which originally appeared on PodcastNotes
Lex Fridman Podcast #189 with David Sinclair - June 6, 2021
Edited for content and readability - Images sourced from Pexels

Key Takeaways

  • Wearables have the potential to revolutionize medicine
  • The goal is doctors being able to look at a dashboard of our body based on swabs, blood tests, and biosensors and make real-time, tailored recommendations
  • Top causes of aging: broken chromosomes, cell stress, smoking
  • Lifestyle methods to slow aging: fasting (skip 1-2 meals per day), eat more vegetables and less red meat, exercise, get good quality sleep (quality more important than quantity)

Introduction

Dr. David Sinclair (@davidsinclair) is a biologist, professor of genetics at Harvard, author, and expert on aging and longevity. His research and biotech companies focus on understanding why we age and how to slow its effects.

In this episode of the Lex Fridman Podcast, Lex and guest David Sinclair discuss the determinants of why we age, solving aging, the trend of wearables and tracking health data, artificial intelligence, social perspectives of lifespan , and death, and lifestyle factors to improve lifespan.

Host: Lex Fridman (@lexfridman)

Book: Lifespan: Why We Age and Why We Don’t Have To by David Sinclair

Artificial Intelligence & Immortality

  • We live in a time we can leverage data to have the pieces of the life of people we can gather using technology, beyond just written books
  • AI makes it possible to bring back people that we love in some way and in essence achieve immortality
  • AI can be used to build experience, thoughts, speech
  • AI uses in aging: generate biological clocks, predict protein folding, assemble genomes, predict longevity in mouse in response to stimuli, diagnosing a virus

David Sinclair Interest And Predictions On Wearables

  • Wearables represent the merging of machines and humans  
  • Wearables help us collect biological data about our bodies
  • We can use data to keep ourselves in optimal shape
  • “Picture a future where you’re monitored constantly so you wouldn’t have a heart attack, you’d know that was coming.” – David Sinclair
  • It’s feasible that wearables and similar technology will indicate what antibiotic or medication to take, what to eat, etc. – and augment physicians who would just need to sign off on the protocol
  • COVID-19 accelerated biological technologies & medical advances
  • There will be day doctor’s use wearable technology to send patients home for monitoring instead of keeping them in the hospital
  • Wearables will revolutionize medicine – it can collect data which can be used to predict sickness, diagnose disease

InsideTracker

  • InsideTracker: David Sinclair co-founded a company that creates personalized and actionable plans to help people optimize their bodies through nutrition, supplements, and lifestyle
  • Connects scientific papers to individual data and make recommendations for lifestyle
  • InsideTracker leverages hundreds of thousands of human data points and thousands of scientific articles to create a formula of what works and what doesn’t for your body
  • Recommendation of food and nutrition was better than leading drug at treating type 2 diabetes
  • Soon, the current model of medicine is going to outdated as machines and data will know us better than our doctor
  • “We wouldn’t drive a car without a dashboard so why would doctors do the same?” – David Sinclair

How And Why We Age

  • Aging is both a feature and bug of evolution
  • We only need to live as long as we need to in order to replace ourselves – some breed slowly and build a body that lasts, some breed quickly and die quickly
  • We can do better at aging
  • Hallmarks of aging include: loss of telomeres, senescent cells, loss of energetics
  • Defining factor of aging: preservation of information and loss of entropy
  • “Loss of information in our bodies is a root cause of aging.” – David Sinclair
  • We have information regulator genes in our bodies – upregulation could preserve health
  • Information in cells = DNA and epigenome
    • DNA is usually intact in animals and humans over time
    • Epigenome: regulators of genetic information
  • Question of importance: is there a repository of information in the body to restore from?
  • Antagonistic pleiotropy: a system built to keep us alive when we’re young but has damaging effects later in life
  • Causes of aging: (1) broken chromosomes and (2) cell stress – smoking also dramatically accelerates biological age
    • It’s hard to repair something that’s constantly breaking: we have 1000 chromosome breaks per day – the break is recognized by proteins and is usually fixed but not always
  • You can slow down aging using three embryonic genes to reset the age of tissues to a certain point – but if you don’t do it right it can cause tumors  

Data Sharing In Biology

  • “We’re living through what’s going to be seen as one of the biggest revolutions in human health through the gathering of data about our bodies.” – David Sinclair
  • Ultimately, we’re all going to be monitored
  • There will be a reversal where blamed will be assigned for not collecting data
  • Decisions are made based on very few tests when we have the opportunity to collect more
  • Consumer health is going in the direction of the patient having access to better data than the doctor (through private lab tests, biotech companies, etc.)
  • Doctors are becoming excited and interested about seeing and using privately collected patient data to make more informed decisions
  • The U.S. currently spends 17% of GDP on healthcare – we can save money by monitoring using wearables and prevention
  • Ideally, we can create a system where we can share data as we’d like and keep what we wouldn’t

Lifestyle Methods To Slow Aging

  • Fasting is one of the oldest ways to improve health – we need to optimize how long and the frequency
  • “If there’s one thing I can recommend to anybody to slow down aging it’s to skip a meal or two a day.” – David Sinclair
  • Note: David Sinclair is a big fan of one meal a day; the carnivore diet has made Lex feel really good
  • When you eat seems to be more important than what you eat
  • Data says plant-based foods are better than meat-based foods
    • People who live longer tend to eat Mediterranean diets with little red meat
    • High meat consumption stimulates mTor
    • Could take rapamycin to counteract effects of meat
    • Meat produces immediate health benefits (muscle, energy) but potentially at the expense of long term effects
  • Eat a diet full of leafy greens, avoid spikes in sugar, possibly explore supplementing with resveratrol
  • Exercise clearly extends longevity
  • You don’t need much exercise to get great benefit – exercise aerobically a few times per week (even 10 minutes) and lift weights a few times per week
  • Sleep is critical for longevity to avoid premature aging and adverse health outcomes
  • Sleep quality seems to matter more than quantity
  • The brain is the center for longevity so we have to take care of stress levels, mental health

Data Collection Methods

  • We’ll likely work to moving away from blood draws for data
  • Currently: swab and ship to the lab to test hormones, stress levels, blood glucose, etc.
  • In the next 10 years: spit on paper and stick in a machine for analysis
  • Home tests are really easy and scalable if they can become democratized (price reduced)

Realistic Goals Of Lifespan

  • If you start eating cleaner in your 20s, that has been shown to improve lifespan in animal models
  • If you are in your 20s, aim to reach 100
  • There’s no maximum limit to human lifespan

Death & Denial

  • We seem to draw meaning from life being rooted in our existence – most of us find it distressing to face our own mortality
  • All living beings have evolved to want to live and survive
  • It’s possible we evolve to naturally deny aging because we need to use our energy and focus for innovation and life instead of death
  • It might be easier to be lazy if you are immortal

Note: Wearable Oura ring was referred to multiple times throughout the show

How mRNA and DNA vaccines could soon treat cancers, HIV, autoimmune disorders and genetic diseases

The idea of using genetic material to produce an immune response has opened up a world of research and potential medical uses far out of reach of traditional vaccines. Deborah Fuller is a microbiologist at the University of Washington who has been studying genetic vaccines for more than 20 years. We spoke to her about the future of mRNA vaccines.

Below are excerpts from that conversation which have been edited for length and clarity.

This article is a repost which originally appeared on The Conversation
Deborah Fuller - January 6, 2022
Edited for content and readability - Images sourced from Pexels

Our Takeaways:

  • Nucleic acid vaccines are based on the idea that DNA makes RNA and then RNA makes proteins.
  • These vaccines are effective at inducing a T cell response.
  • For cancer, the goal is to make your body better able to recognize the very specific neoantigens the cancer cell has produced and destroy it.
  • For autoimmune disorders, the vaccine would suppress the T Cells to keep the immune system from attacking myelin

How long have gene-based vaccines been in development?

This type of vaccine has been in the works for about 30 years. Nucleic acid vaccines are based on the idea that DNA makes RNA and then RNA makes proteins. For any given protein, once we know the genetic sequence or code, we can design an mRNA or DNA molecule that prompts a person’s cells to start making it.

When we first thought about this idea of putting a genetic code into somebody’s cells, we were studying both DNA and RNA. The mRNA vaccines did not work very well at first. They were unstable and they caused pretty strong immune responses that were not necessarily desirable. For a very long time DNA vaccines took the front seat, and the very first clinical trials were with a DNA vaccine.

But about seven or eight years ago, mRNA vaccines started to take the lead. Researchers solved a lot of the problems – notably the instability – and discovered new technologies to deliver mRNA into cells and ways of modifying the coding sequence to make the vaccines a lot more safe to use in humans.

Once those problems were solved, the technology was really poised to become a revolutionary tool for medicine.

What makes nucleic acid vaccines different from traditional vaccines?

Most vaccines induce antibody responses. Antibodies are the primary immune mechanism that blocks infections. As we began to study nucleic acid vaccines, we discovered that because these vaccines are expressed within our cells, they were also very effective at inducing a T cell response. This discovery really prompted additional thinking about how researchers could use nucleic acid vaccines not just for infectious diseases, but also for immunotherapy to treat cancers and chronic infectious diseases – like HIV, hepatitis B and herpes – as well as autoimmune disorders and even for gene therapy.

How can a vaccine treat cancers or chronic infectious diseases?

T cell responses are very important for identifying cells infected with chronic diseases and aberrant cancer cells. They also play a big role in eliminating these cells from the body.

When a cell becomes cancerous, it starts producing neoantigens. In normal cases, the immune system detects these neoantigens, recognizes that something’s wrong with the cell and eliminates it. The reason some people get tumors is that their immune system isn’t quite capable of eliminating the tumor cells, so the cells propagate.

With an mRNA or DNA vaccine, the goal is to make your body better able to recognize the very specific neoantigens the cancer cell has produced. If your immune system can recognize and see those better, it will attack the cancer cells and eliminate them from the body.

This same strategy can be applied to the elimination of chronic infections like HIV, hepatitis B and herpes. These viruses infect the human body and stay in the body forever unless the immune system eliminates them. Similar to the way nucleic acid vaccines can train the immune system to eliminate cancer cells, they can be used to train our immune cells to recognize and eliminate chronically infected cells.

What is the status of these vaccines?

Some of the very first clinical trials of nucleic acid vaccines happened in the 1990s and were for cancer, particularly for melanoma.

Today, there are a number of ongoing mRNA clinical trials for the treatment of melanoma, prostate cancer, ovarian cancer, breast cancer, leukemia, glioblastoma and others, and there have been some promising outcomes. Moderna recently announced promising results with its phase 1 trial using mRNA to treat solid tumors and lymphoma

There are also a lot of ongoing trials looking at cancer DNA vaccines, because DNA vaccines are particularly effective in inducing T cell responses. A company called Inovio recently demonstrated a significant impact on cervical cancer caused by human papilloma virus in women using a DNA vaccine.

Can nucleic acid vaccines treat autoimmune disorders?

Autoimmune disorders occur when a person’s immune cells are actually attacking a part of the person’s own body. An example of this is multiple sclerosis. If you have multiple sclerosis, your own immune cells are attacking myelin, a protein that coats the nerve cells in your muscles.

The way to eliminate an autoimmune disorder is to modulate your immune cells to prevent them from attacking your own proteins. In contrast to vaccines, whose goal is to stimulate the immune system to better recognize something, treatment for autoimmune diseases seeks to dampen the immune system so that it stops attacking something it shouldn’t. Recently, researchers created an mRNA vaccine encoding a myelin protein with slightly tweaked genetic instructions to prevent it from stimulating immune responses. Instead of activating normal T cells that increase immune responses, the vaccine caused the body to produce T regulatory cells that specifically suppressed only the T cells that were attacking myelin.

Any other applications of the new vaccine technology?

The last application is actually one of the very first things that researchers thought about using DNA and mRNA vaccines for: gene therapy. Some people are born missing certain genes. The goal with gene therapy is to supply cells with the missing instructions they need to produce an important protein.

A great example of this is cystic fibrosis, a genetic disease caused by mutations in a single gene. Using DNA or an mRNA vaccine, researchers are investigating the feasibility of essentially replacing the missing gene and allowing someone’s body to transiently produce the missing protein. Once the protein is present, the symptoms could disappear, at least temporarily. The mRNA would not persist very long in the human body, nor would it integrate into people’s genomes or change the genome in any way. So additional doses would be needed as the effect wore off.

Research has shown that this concept is feasible, but it still needs some work.

Proteins could be key to long and healthy life

Developing drugs that target these proteins could be one way of slowing the ageing process, according to the largest genetic study of ageing.

This article is a repost which originally appeared on The University of Edinburgh
The University of Edinburgh - January 24, 2022
Edited for content and readability - Images sourced from Pexels
Source: https://www.nature.com/articles/s43587-021-00159-8

Our Takeaway:

  • 2 proteins are identified to have significant negative effects across ageing measures.
  • Individuals with raised levels these 2 proteins (LPA & VCAM1), are less likely to live longer lives.
  • High levels of LPA can increase the risk of atherosclerosis. Heart disease and stroke is also possible.
  • VCAM1 helps with blood clotting and the immune response and increases when it has detected an infection.
  • Studies are being done to lower these proteins when elevated.

As we age, our bodies begin to decline after we reach adulthood, which results in age-related diseases and death. This latest research investigates which proteins could influence the ageing process.

Many complex and related factors determine the rate at which we age and die, and these include genetics, lifestyle, environment and chance. The study sheds light on the part proteins play in this process.

Inheritance

Some people naturally have higher or lower levels of certain proteins because of the DNA they inherit from their parents. These protein levels can, in turn, affect a person’s health.

University of Edinburgh researchers combined the results of six large genetic studies into human ageing – each containing genetic information on hundreds of thousands of people,

Among 857 proteins studied, researchers identified two that had significant negative effects across various ageing measures.

People who inherited DNA that causes raised levels of these proteins were frailer, had poorer self-rated health and were less likely to live an exceptionally long life than those who did not.

Protein roles

The first protein, called apolipoprotein(a) (LPA), is made in the liver and thought to play a role in clotting. High levels of LPA can increase the risk of atherosclerosis – a condition in which arteries become clogged with fatty substances. Heart disease and stroke is a possible outcome.

The second protein, vascular cell adhesion molecule 1 (VCAM1), is primarily found on the surfaces of endothelial cells – a single-cell layer that lines blood vessels. The protein controls vessels’ expansion and retraction – and function in blood clotting and the immune response.

Levels of VCAM1 increase when the body sends signals to indicate it has detected an infection, VCAM1 then allows immune cells to cross the endothelial layer (a thin membrane that lines the inside of the heart and blood vessels), as seen for people who have naturally low levels of these proteins.

Improved ageing

The researchers say that drugs used to treat diseases by reducing levels of LPA and VCAM1 could have the added benefit of improving quality and length of life.  

One such example is a clinical trial that is testing a drug to lower LPA as a way of reducing the risk of heart disease.

There are currently no clinical trials involving VCAM1, but studies in mice have shown how antibodies lowering this protein’s level improved cognition during old age.

The findings have been published in the journal Nature Aging.

Breakthrough into the cause of male infertility

Scientists at Newcastle University have identified a new genetic mechanism that can cause severe forms of male infertility.

Our Takeaway:

  • Scientists collected and studied DNA from 185 infertile men and their parents. They identified 145 rare protein-altering mutations that are likely to negatively impact male fertility.
  • As many as 29 of the mutations affect genes directly involved in processes related to spermatogenesis — the process of sperm cell development.
  • Experts have found that mutations occurring during the reproduction process, when the DNA of both parents is replicated, can result in infertility in men later in life.
This article is a repost which originally appeared on ScienceDaily
Newcastle University - JANUARY 10, 2022
Edited for content and readability - Images sourced from Pexels
Source: https://www.ncl.ac.uk/press/articles/latest/2022/01/maleinfertilitystudy/

This breakthrough in understanding the underlying cause of male infertility offers hope of better treatment options for patients in the future.

The study, published today in Nature Communications, shows that new mutations, not inherited from father or mother, play a major role in this medical condition.

Improving understanding

It is hoped that this new knowledge will help to provide more answers in the future about the cause and best treatment options available to infertile couples.

Professor Joris Veltman, Dean of Newcastle University’s Biosciences Institute, UK, led the research which involved patients from Newcastle Fertility Centre and Radboud University Medical Centre in the Netherlands.

He said: “This is a real paradigm shift in our understanding of the causes of male infertility. Most genetic studies look at recessively inherited causes of infertility, whereby both parents are a carrier of a mutation in a gene, and the infertility occurs when the son receives both mutated copies, resulting in problems with their fertility.

“However, our research has found that mutations which occur when the DNA is replicated during reproduction in parents plays a significant role in the infertility in their sons.

“At present, we don’t understand the underlying cause in the majority of infertile men, and this research will hopefully increase the percentage of men for whom we can provide answers.”

Scientists collected and studied DNA from a global cohort of 185 infertile men and their parents. They identified 145 rare protein-altering mutations that are likely to negatively impact male fertility.

As many as 29 of the mutations affect genes directly involved in processes related to spermatogenesis — the process of sperm cell development — or other cellular processes related to reproduction.

Experts identified mutations in the gene RBM5 in multiple infertile men. Previous research carried out in mice has shown that this gene plays a role in male infertility.

Importantly, these mutations mostly cause a dominant form of infertility, where only one mutated gene is required. As a consequence, there is a 50% chance that infertility caused by these mutations will be passed on to the man’s child (if assisted reproductive technologies are used) and this may result in infertility, particularly in sons.

Millions of children have already been born through assisted reproductive approaches as a result of infertility. This research indicates a significant proportion of these children may inherit infertility from their father.

Professor Veltman said: “If we are able to obtain a genetic diagnosis, then we can start understanding better male infertility problems and why some infertile men still produce sperm that can be used successfully for assisted reproduction.

“With our information, and the research others are doing, we hope clinicians can improve counselling for couples and recommend what is the best course of action in order to conceive, either by proposing an appropriate medically-assisted procedure or in cases where none is suitable, provide appropriate alternatives.”

Infertility problems

It is estimated that up to 7% of men are affected by infertility and 50% of fertility problems within a heterosexual couple are due to the man. In around half of male infertility cases, the cause is unexplained.

Moving forwards, the scientists want to expand their work by studying thousands of patients and their parents in a large international consortium.

They will follow-up their research by conducting further studies into the role these newly identified mutated genes have on the impact of spermatogenesis and on the overall fertility in humans.

An at-home DNA test promises to tell you what strain of weed is best for you, and what kind will make you paranoid

Many people swear off weed after taking too much of an edible on one occasion. Ending up anxiously couch-locked is no one’s idea of a good time, but what if there was a test to tell you a better way to get high?

This article is a repost which originally appeared on Insider
Andrea Michelson - October 4, 2021
Edited for content and readability Images sourced from Pexels
  • Endocanna Health offers a DNA test that tells you how to use cannabis better.
  • The analysis looks at genetic hallmarks that may influence how you respond to drugs.
  • With those genes in mind, the company says it can recommend a personalized profile.

Endocanna Health is offering a DNA test that claims to do just that for $199. Its team of scientists have identified 57 genetic signatures that may influence someone’s response to cannabis. From there, the company can recommend certain doses or formulations of cannabis for a customer’s specific needs.

Users can swab themselves at home with an Endo·dna test kit or send in data from another service like 23andMe for a smaller fee.

The company markets itself as “the future of personalized cannabinoid therapeutics,” founded with precision medicine in mind. Other companies such as HaluGen have created similar tests that screen for sensitivity to ketamine, mushrooms, and other psychedelics that are now being used for therapeutic purposes.

Your genetics affect how you respond to drugs

The Endocanna test considers a person’s response to THC, the compound in cannabis that’s associated with the high, along with the other parts of the plant. While some people feel relaxed or giddy after consuming THC, approximately 31% of the general population has reported an adverse reaction to the drug, according to Endocanna.

Studies have hinted at a genetic basis for how people respond to drugs: whether they’re predisposed towards anxiety and psychosis, or if they might have a greater tendency to become addicted.

Scientists haven’t identified a specific piece of genetic code that predicts a bad trip, but they have named some genes of interest. The AKT1 gene, for one, has a variant that’s been potentially linked to a higher risk of psychosis in people who use cannabis.

Other genes may be connected to unhealthy use of cannabis and other drugs. The National Institute on Drug Abuse estimates that 30% of people who use cannabis do so problematically, with some cases qualified as addiction. The gene CHRNA2 has also caught scientists’ interest as a potential factor in cannabis use disorder.

The test might tell you to avoid THC completely, or opt for a cannabis strain with higher levels of CBD, another cannabinoid that won’t get you high. Someone who tends to get anxious when using weed might opt for a high CBD to THC ratio for pain relief without the psychoactive risks.

Endocanna also says it considers terpenes, another type of cannabis compound that may affect the brain, when creating a personalized cannabis profile based on genetic information.