The Biology of Aging and Longevity

Over the last few decades, technologies such as gene sequencing have revolutionized the way we understand aging and its implications for disease. Aging means a different thing than it did just a few decades ago, opening up a number of new strategies and technologies to deal with its effects.

Today, longevity research and geroscience aim to prevent and delay age-related disease (ARD) and increase healthspan. This is related to, but not the same as, lifespan. Healthspan is the period of a person’s life where they are not burdened with one of many chronic age related diseases and can live a normal, active lifestyle. Whereas lifespan, of course, is the total duration of a person’s life. While researchers are interested in expanding the total lifespan of individuals, another essential and often overlooked component of improving aging and longevity is increasing a person’s healthspan as a subset of their total lifespan.

Researchers are tending toward the conclusion that aging itself is a disease that causes ARDs, and that aging can and should be treated as a disease. They are increasingly interested in exploring lifestyle changes and clinical interventions that may be able to extend a person’s healthspan and delay many ARDs.

What We Can Learn from Genetics and Centenarians

Centenarians (people who live to the age of 100) are extremely rare, with only 1 out of 5000 people reaching that age.
1 out of 250,000 people reach semi-supercentenarian status, achieved at the age of 105. Supercentenarians are even rarer, with only 1 out of every 5 million people reaching the age of 110+.
While people age differently at ages beyond 100, as they get older than that, they begin to show similar phenotypes and display more and more similarities to each other.
Around 90% of people who will reach the age of 100 do not develop ARDs or disabling diseases throughout their early 90’s.
By the age of 100, only 15% of people remain unaffected by disabling diseases.
However, supercentenarians are more genetically similar to each other, with 70% of them escaping age-related diseases by the age of 100.
In order to live to age 90, around 75% of the way you age is determined by your health behaviors. If you’re lucky enough to live to 105+, around 75% of how you age is determined by around 200 special protective genes.
It’s likely that semi-supercentenarians and supercentenarians still have ARD related genes, but also have these protective genes.
It may be possible to isolate these protective genes and translate their effect into future medicines.
New studies are trying to discover the genetic resiliencies that centenarians have for diseases like alzheimers. Many centenarians have genetic markers suggesting that they might be predisposed to alzheimers, but then never display symptoms in later years.

How Ketones Can Help Us Understand Aging

Ketones are molecules that the body can produce and use as fuel when carbohydrate availability is low. Evolutionarily, ketones probably developed as a mechanism to fuel brain function when the body is starving. However, most organs in the body can also use ketones as fuel.
We’ve more recently come to understand that ketones are not just fuel. They also bond directly to proteins, producing specific signaling effects which trigger helpful biological processes that intersect with aging.
Active ketobodies may play a role in the expansion of lifespan and healthspan.
Research has revealed that many people who will go on to develop chronic cognitive decline first experience a decrease in the ability of the brain to metabolise glucose. However, brain ketone metabolization ability appears to be unaffected in this group.
Giving aging people regular ketone supplements seems to improve brain energy and function, possibly rescuing their brains from energy starvation and decline. Studies have shown that patients who receive these ketone diets demonstrate evidence of cognitive improvement.
During aging, the heart often displays signs of metabolic decline and energy supply disruption. Ketone supplements may also be able to rescue the heart and cardiac system from the effects of this decline, reducing oxidative stress, inflammation, and fibrosis.
Ketones seem to act as signaling metabolites through receptor bindings and epigenetic mechanisms.

Is Fasting the Answer?

Specific types of fasting have proven to reliably expand both lifespan and healthspan. This has a profound effect on most major chronic illnesses, including neurodegenerative, cardiovascular, and autoimmune diseases.
Importantly, fasting does so without adding anything to the individual’s system. Fasting simply triggers a person’s natural protective and regenerative processes.
Companies are decoding the effects of human fasting and trying to replicate them with low-impact drugs.
One way to do this is to supplement individuals with the chemicals and molecules that their body would naturally produce during a prolonged fast. By recreating the physiological effects of fasting, these drugs may be able to improve health outcomes.
Studies show that 36 hour fasts improve plasma’s ability to reduce inflammation, have protective antioxidant effects, and produce cardioprotective effects.
Traditional fasting produces profound effects on the body’s metabolic state, significantly changing the state of at least 300 metabolites. Four of these metabolites seem to be able to synergistically replicate all of the beneficial effects that normal fasting has on the body.
Researchers posit that supplementing a diet with a fasting mimetic drug can help reduce the compromising effects that eating has on plasma anti-inflammatory ability, plasma antioxidant ability, and plasma cholesterol efflux ability.
A study done on a population of roundworms found that regularly taking this fasting mimetic supplement increased their lifespan by a median of 96%. Compared to a control group of worms that were denied food in order to activate a traditional fasting response, the population given the fasting mimetic lived longer.
By combing through different natural responses to different conditions, researchers may be able to develop further mimetic supplements that increase health outcomes.

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Consideration

With 2021 well underway and with public markets still strong, we think it is an important time to highlight some of the key private market, venture investment themes that iSelect fund has identified for the year. We believe technologies transforming the Agriculture, Food and Wellness markets will flourish, with a focus on four areas: technologies that enable better food choices to drive better health outcomes, technologies that drive better, more profitable farm operations, technologies that drive the Consumerization of Healthcare, and biome-based treatment technologies. At iSelect, we invest for impact AND performance. We offer qualified investors access to emerging growth companies through our national venture capital strategy. Our unique structure allows our investors to continue to invest in these companies as they develop.

Timing

Why is now the right time for venture? The answer is that now is not explicitly the right time. Venture is something we need in our economy at all times. Now is not better than any other particular time. The question is, why ever stop? When we look at the challenges we’re facing in food and healthcare the reality is there is someone, somewhere who has an insight about how to build a product that will solve those problems. And if they put the right resources to it, they will succeed. As long as we need new technology to make life better or make our lives more enjoyable, we need venture capital to help fuel those entrepreneurs.

What is iSelect as a product?

iSelect is a very unique product, but when you break it into its parts it’s fairly easy to understand. On the front end we’re a traditional venture capital fund. We have a diligence process. We have an investment process. We have categories of industries where we have focus and real expertise, and we invest in companies in those areas that meet requirements for the fund. On the back end we’re unique in that we don’t raise a large amount of capital at one time and deploy it over the life of our fund. Each deal that we bring onto the fund, our investors have to prove and determine to invest in that deal. We have to constantly prove our diligence standards. It’s accessible, transparent and easy for investors to come in and see our comprehensive process.

What is the ideal iSelect company?

We are looking for founders that are passionate and we want the problem they’re trying to solve to be big, real, and painful. We want the solution to be revolutionary and we want our capital to be able to help them solve that problem. We want to know that they have customers involved and that the solution they’ve come up with actually meets those customers’ and market needs. And we want the team to be capital efficient with the money they’re spending.

What does the ideal iSelect company look like?

We’re looking for a company that has an opportunity to have a 10x return to our investment or greater in a period of three to seven years. What excites us at iSelect are companies that are solving big problems. We want companies that are going to be the Monsantos of the future. Not just in the size and the scope, but the impact they have on people’s lives. We want to create positive impacts on people’s lives, so we invest in areas like agricultural production and areas like producing healthy foods for our kids. They are problems that impact real people’s lives on a daily basis. That’s what we’re trying to do at iSelect. We’re trying to solve the big problems out there. Find ways to bring capital to the entrepreneurs who are the real heroes out there getting up every morning, beating away at these things that are problems that you and me and everyone else faces in their everyday lives.

What is iSelect?

iSelect is a venture capital firm. What that means is we look at hundreds and hundreds of different companies and we apply tough diligence standards to each of them, looking at whether the team has a good plan for growing the business, whether the team is qualified and credible, and more. We do that to resolve the few who provide the best opportunities for investors. And then iSelect takes that smaller set of investments and goes to investors who are interested in venture capital and provides a way for them to invest in these companies, either individually or all at once. We co-invest alongside other venture capitalists. We source transactions through to an exit where the company would become public or get bought. And we manage that whole investment process on behalf of our investors.