What is Aging?

Summary

Aging is a complex process involving a decline in bodily functions and increased vulnerability to diseases. Despite limited understanding of its mechanisms, evolutionary theories and cellular changes like DNA damage and telomere shortening are explored. Notable examples of species with extended lifespans and cancer resistance, such as the naked mole rat, demonstrate aging's plasticity. Scientific breakthroughs in gene manipulation and interventions like caloric restriction have shown potential in extending life and healthspan, offering hope for future aging research.

Takeaways

• 📉 Aging is a complex process involving a decline in the body's ability to respond to stress and an increased vulnerability to diseases.
• 🤒 Influenza, a common illness, is a significant cause of mortality among the elderly.
• 🧬 The mechanisms of aging are not well understood, and the evolutionary pressures that shaped our lifespan have historically been different.
• 🧬 DNA damage, free radical theory, and telomere shortening are among the hypotheses proposed to explain the aging process.
• 📈 After age 30, the mortality rate doubles approximately every eight years, a pattern observed across human populations.
• 🐦 Birds and the naked mole rat are examples of species that defy typical aging patterns, suggesting that longevity can be influenced by environment and genetics.
• 🦡 The naked mole rat is of particular interest due to its resistance to cancer and long lifespan.
• 🧬 Genetic manipulation can significantly impact aging, with certain gene modifications in mice leading to either accelerated aging or extended lifespan.
• 🥗 Caloric restriction, limiting food intake while maintaining nutrient intake, has been shown to extend lifespan and healthspan in rodents.
• 🧪 Bioinformatics and experimental work are used to identify genes that modulate longevity and understand the pathways they regulate.
• 💡 Aging research is time-consuming and costly, but slowing down the aging process could halve the incidence of age-related diseases at every age.

Q & A

What is aging and how does it affect our bodies?

Aging is an age-related decrease in viability and increase in vulnerability, meaning our capacity to respond to external stresses and function decreases with age, making us more susceptible to diseases.

Why is aging difficult to study?

Aging affects different levels, organs, and systems in the body, making it complex. Additionally, the mechanisms of aging, such as why we age and what drives the process from a cellular perspective, are still poorly understood.

How has the human lifespan changed over the past centuries?

The lifespan has significantly increased; 150 years ago, it was around 40 years old, and a thousand years ago, it was approximately 25 years old.

What evolutionary pressures have there been regarding aging?

In the past, most animals died young, so there was little evolutionary pressure to avoid aging or live longer.

What are some theories about the causes of aging?

Theories include DNA damage affecting cell renewal and stem cells, the free radical theory which involves oxidative stress from mitochondria, and telomere shortening with cell division.

How does the mortality rate change with age in human populations?

After about age 30, the chances of dying double every eight years, which is a standard pattern across human populations regardless of geographical location.

What is unique about the aging process in birds?

Birds live longer than expected for their body size, possibly due to their ability to fly and avoid predators.

Why do naked mole rats live longer than expected?

Naked mole rats live over 30 years because they live in a protected environment and have evolutionary reasons to live longer, including being extremely cancer resistant.

How can genes be manipulated to impact aging?

Manipulating individual genes can significantly impact aging. For example, manipulating DNA repair systems can lead to accelerated aging, while turning off the growth hormone receptor gene in mice can increase lifespan by 50%.

What is caloric restriction and how does it affect lifespan?

Caloric restriction involves limiting the number of calories consumed while maintaining adequate nutrients, which has been known to extend lifespan by up to 50% in rodents and keep them healthier for longer.

How does the speaker's lab approach the study of aging?

The lab uses a mix of bioinformatics and experimental work to identify genes that modulate longevity, looking for common patterns and key regulators of aging pathways.

What would be the impact of slowing down the aging process by seven years?

Slowing down the aging process by seven years would halve the incidence of age-related diseases at every age, significantly impacting human lifespan and health.

Why did the speaker become interested in studying aging?

The speaker became interested in studying aging at a young age, motivated by the desire to find a solution to prevent aging and death.

Outlines

00:00

🧓 Aging and Its Complexities

Aging is described as a decline in vitality and an increase in susceptibility to diseases with age. The capacity to respond to external stresses and to function properly diminishes, making individuals more vulnerable to illnesses such as influenza. Aging affects different body systems and organs, complicating research into its mechanisms. Despite some evolutionary theories and hypotheses like DNA damage affecting cell renewal and the free radical theory linking oxidative stress to aging, the exact reasons and processes behind aging remain poorly understood. Telomeres, the protective tips of chromosomes, also play a role as they shorten with age, potentially contributing to aging. The mortality rate doubles every eight years after the age of 30, a pattern observed across human populations regardless of geographical location or initial mortality rates. However, there are exceptions like birds and the naked mole rat, which live longer than expected due to their unique characteristics and environments, suggesting that longevity can be influenced by evolutionary pressures and genetic factors.

Keywords

💡Aging

Aging refers to the biological process involving the gradual decline in the functional ability of an organism over time. It is central to the video's theme, which discusses how aging affects an individual's response to stress and increases vulnerability to diseases. The script mentions that 'aging is an age-related decrease in viability and increase in vulnerability', highlighting the impact of aging on health and longevity.

💡Viability

Viability in the context of the video refers to the ability of an organism to survive and function effectively. The script connects viability with aging, stating that 'your capacity to respond to external stresses, and your capacity to function, decreases with age', indicating that as organisms age, their viability diminishes.

💡Influenza

Influenza, commonly known as the flu, is mentioned as a major cause of mortality in the elderly. It exemplifies how aging can increase susceptibility to diseases, which is a key point in the discussion about the effects of aging on health.

💡DNA Damage

DNA Damage is discussed in the video as a potential cause of aging. It is suggested that damage to DNA can affect cell renewal and stem cells, which in turn hinders the body's ability to repair itself. The script states, 'There's damage to DNA, that then probably affects cell renewal and stem cells', illustrating the role of DNA damage in the aging process.

💡Free Radical Theory

The Free Radical Theory of aging posits that reactive compounds generated during cellular respiration cause oxidative stress, leading to cumulative damage over time. This theory is mentioned in the script as a possible explanation for aging, with the statement 'This idea that as mitochondria in our cells... generates these very highly reactive compounds, which creates damaging oxidative stress'.

💡Telomeres

Telomeres are the protective caps at the end of chromosomes that shorten with each cell division. The video discusses how the shortening of telomeres with age might contribute to the aging process. The script mentions 'Telomeres are the tips of chromosomes and they shorten with cell division', linking telomere length to aging.

💡Mortality Rate

The mortality rate refers to the rate at which individuals within a population die. The video uses the doubling of mortality every eight years after age 30 as a standard pattern to illustrate the increasing risk of death with aging.

💡Naked Mole Rat

The naked mole rat is highlighted in the video as an example of an organism that lives much longer than expected for its body size. It is noted for its resistance to cancer and its protected environment as factors contributing to its longevity, showcasing the variability in aging across species.

💡Cancer Resistance

Cancer resistance is mentioned in relation to the naked mole rat's extraordinary longevity. The video states that 'there's not been a single case of cancer in hundreds of naked mole rats', suggesting that certain species have evolved mechanisms to resist aging-related diseases.

💡Caloric Restriction

Caloric Restriction is a dietary intervention discussed in the video that involves reducing the intake of calories while maintaining adequate nutrition, known to extend lifespan in rodents. It is presented as a potential method to modulate aging, with the script stating that 'Caloric Restriction... has been known for decades to extend life span in rodents like 50%'.

💡Gene Manipulation

Gene manipulation is discussed as a breakthrough in the field of aging research, where altering specific genes can have significant impacts on the aging process. The script mentions that 'you can turn off a single gene in mice like growth hormone receptor, and increase life span by 50%', illustrating the potential of genetic interventions to extend life and health.

Highlights

Aging is a complex process affecting different organs and systems.

Aging increases vulnerability to diseases like influenza.

Mechanisms of aging are not well understood at a cellular or molecular level.

Evolutionary perspective suggests little pressure to avoid aging in the past.

DNA damage affects cell renewal and contributes to aging.

Free radical theory links oxidative stress to aging.

Telomeres shorten with age, potentially driving the aging process.

After age 30, mortality risk doubles every eight years.

Birds live longer than expected due to their ability to fly and avoid predators.

Naked mole rats live over 30 years due to a protected environment and evolutionary pressure.

Naked mole rats are extremely cancer resistant.

Longevity is plastic and can be manipulated by genes and evolution.

Some species, like turtles, appear not to age.

Manipulating individual genes can significantly impact aging.

Caloric restriction extends lifespan in rodents by 50%.

Bioinformatics and experimental work are used to identify genes that modulate longevity.

If a gene mediates the effects of caloric restriction, it could be a target for anti-aging drugs.

Aging research is time-consuming and expensive.

Slowing down aging by seven years could halve the incidence of age-related diseases.

Aging is mutable and can be manipulated by diet, genes, and evolution.

The potential to find a solution to aging and death exists.

Transcripts

Aging is an age-related decrease in viability and increase in vulnerability.

It means that, your capacity to respond to external stresses, and your capacity to function

decreases with age.

You become more vulnerable to diseases.

One of the major causes of mortality in the elderly is influenza, which is just the common

flu.

The thing with aging, of course, it entails different levels and different organs and

different systems in the body, which makes it very complex and relatively difficult to

study.

We actually don't know much about aging in the sense of its mechanisms.

Why we age, what drives the process of aging from a cell or molecular perspective--is still

relatively poorly understood.

I mean, if you look at it evolutionary, our life span only recently has been so long.

I mean the life span 150 years ago was something like 40 years old.

And a thousand years ago it was maybe 25.

When our species evolved and when most species evolved, most of the animals die when they're

young.

So there was really no pressure or very weak pressure, for us to avoid aging or to live

longer.

There are hypotheses, for example:

That there's damage to DNA, that then probably affects cell renewal and stem cells, which,

in turn, prevents repairing the body and contributes to loss of viability.

Then there's the free radical theory of aging.

This idea that as mitochondria in our cells, as they burn energy with oxygen, it generates

these very highly reactive compounds, which creates damaging oxidative stress, which in

turn accumulates with age, and that's the cause of aging.

There's also things like the telomeres.

So Telomeres are the tips of chromosomes and they shorten with cell division.

But because it occurs with age as well, people say, well maybe, this drives the process of

aging.

So after about age 30, your chances of dying double every eight years

This is fairly standard for human populations.

No matter where you're from or where you live...

In a third world country, they may have higher mortality to begin with, but you'll still

see this exponential increase in mortality.

But then you have very unique creatures.

One example are birds.

Now birds actually live longer than would be expected for their body size because, you

know, they can fly and avoid predators.

One of the species that we're interested in is an organism called the naked mole rat.

Which lives over 30 years.

Why?

Because it lives in this protected environment...

Then there is evolutionary reason, there is evolutionary pressure to live longer.

One of the interesting things about the naked mole rat is that it's extremely cancer resistant.

There's not been a single case of cancer in hundreds of naked mole rats.

So longevity is plastic.

Not only are there species that live much longer time than we do, but there are species

that appear not to age.

Like some species of turtles.

Probably one of the greatest breakthroughs in the field so far is that you can manipulate

individual genes and it has a very significant impact on aging.

We know, for instance, that if you start manipulating DNA repair systems, sometimes, say, for example,

in mice, you get what looks like accelerated aging.

On the other hand, you can turn off a single gene in mice like growth hormone receptor

and increase life span by 50%.

There're also interventions that modulate aging.

So the most famous of them all is Caloric Restriction: restricting the amount of calories

animals eat while keeping nutrients like vitamins and minerals healthy.

And this has been known for decades to extend life span in rodents like 50%.

And they're healthier for longer and you know it's quite impressive.

So one of the things, for instance, our lab does, is, well, if you know of a gene that

mediates the effects of caloric restriction, then it may be a suitable target for you to

develop drugs that target that gene in order to have the same effect of caloric restriction

without you having to go on a diet.

Which, let's face it, most people don't want to.

We do a mixture of bioinformatics and experimental work.

We try to look for common patterns amongst these genes as a way to identify new genes

that modulate longevity.

And we want to identify which genes are regulating the other genes, so, key regulators of the

whole pathways.

And the thing to remember about aging in general is that it's very time-consuming and expensive

to do experiments.

That's one of the problems of aging research.

If you could slow down the process of aging just by seven years, this would reduce in

half the incidence of age-related diseases at every single age.

This would have a massive impact on human life span, on human health.

I generally make the analogy of the Wright brothers

They used to look at birds and they said, listen, there are birds.

They are heavier than air, and they can fly.

So if birds can fly, so can we make airplanes.

There's no law of nature that says that aging is immutable.

On the contrary.

What we know now is that aging is surprisingly plastic.

In the sense that it can be manipulated by genes, it can be manipulated by evolution,

it can be manipulated by diet.

When I was younger, I think maybe ten years old, I realized that everyone ages and dies.

And I thought, well, why should that be, I mean, can't we do something about it?

So I thought, well, I'll do it.

I'll study aging and I'll figure it out and I'll find a solution for it.

So people don't have to age and die.