human longevity- camilla warrender

Medical researchers are working feverishly on human aging. Many anticipate the human lifespan to expand naturally as our species evolves. Biotech entrepreneurs are pushing the envelope.

What does it mean for the future of our species?

Lots to think about here. A few questions:

  1. What is the natural length of human life?
  2. What makes us age?
  3. How might we slow aging?
  4. Does lifestyle matter?
  5. Could COVID-19 adversely affect the lifespan of the species?
  6. The long view.

I am Camilla Warrender. Let’s take a look.

What is the natural length of human life?

One of the most prominent debates in the field of aging has raged for a couple of decades between two leading researchers —  epidemiologist S. Jay Olshansky at the University of Illinois, and biologist Steven Austad at the University of Alabama. Their September 2000 wager was whether the first person living to 150 years was already alive.

Dr. Austad bets that those born in the 21st century will have an average life expectancy of 100 years, and a few outliers will live to 150.

Dr. Olshansky expects some extension of the human lifespan, but more likely that we’ll be “increasing years of health, reducing disparities between socio-economic demographics, and diminishing the impacts of the diseases of aging.” In an earlier “Position Statement on Human Aging”, he said: “It is not people that have changed; it is the protected environments in which we live, and the advances made in biomedical sciences and other human institutions, that have permitted more people to attain, or more closely approach, their life-span potential…”

Olshansky’s statement contains a pretty big qualifier. If it’s advanced in biomedical sciences that have allowed more people to approach their potential lifespan, the question looms larger: Given advances, both achieved and imagined, what is that potential?

What makes us age?

Harvard biologist David Sinclair has attracted a lot of attention for his research on slowing the rate of aging and extending the human lifespan. Sinclair has researched the accumulation of senescent or aged cells, and the poor communication between cells that accompanies aging.

His research shows strong evidence that aging results from a loss of information — not in our genome, but in the “epigenome” that turns on and off different parts of our DNA. As we age, this loss of information leads to some cells losing their identity.

Sinclair has focused much of his work on “longevity genes,” and especially sirtuins. Sirtuins make enzymes that protect all organisms from disease and deterioration. These genes maintain the epigenetic information in a cell that helps it to remember its purpose and function.

His research showed that sirtuins need the coenzyme NAD+ (nicotinamide adenine dinucleotide) to work. NAD+ is responsible for hundreds of critical biological processes in our body, including the production of energy, regulation of sleep, and maintenance of healthy DNA.

He also found that the polyphenol resveratrol acts as an NAD+ activator or accelerator.

But as we age, the levels of NAD+ decline. The good news is that two precursors — the NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) molecules  — boost NAD+ levels. While there’s still a debate as to whether NMN or NR is the more effective precursor, Sinclair is betting on NMN. So much so that he takes it each morning, and has his entire family taking it as well.

But that good news is not unqualified. Sinclair also takes pains to clarify that with the current COVID pandemic, there could be risks in taking a ton of NAD+ precursors. Experiments with mice also showed that resveratrol could raise the levels of the ACE2 protein, the enzyme on the outside of the lung cells. And that could offer the coronavirus more opportunity to enter cells.

So especially now, there’s more work to be done.

A quick reminder that Sinclair’s work comes on the shoulders of 2012 Nobel winner stem cell scientist, Shinya Yamanaka. Yamanaka isolated 4 factors that allowed him to reprogram mature cells into immature stem cells, which could then grow into any number of different cells in the body.

That’s something of what the moon jellyfish can do. Often considered close to “immortal,” it can reverse-engineer different types of its own cells, resetting them to an earlier time in its life.

Sinclair experimented with 3 of the 4 factors that Yamanaka had discovered and reversed the aging retinas of mouse subjects in his lab. He effectively reset the epigenome, allowing blind animals to see again — results that Sinclair calls “freakishly exciting.” And he claims he can do that to any tissue in the body.

He’s emphatic as to the potential he sees:  “…cellular age can be fully reset, something I’m convinced we will be able to do one day, without losing our wisdom, our memories, or our souls.”

There is by now a pretty wide consensus among aging researchers that behavioral, dietary, and pharmacologic interventions can delay and even prevent the onset of age-related disease.

So, how else might we slow aging?

Lots of potential on the horizon.

Sinclair, Austad, and other noted researchers are also looking at old drugs that show promise for increased longevity. Rapamycin and metformin are at the top of the list.

Metformin increases the oxygen into a cell, and it has already been used widely (and cheaply) to treat diabetes. It turns out to also have other broad benefits — fewer cancers, and less dementia and heart disease.

Quercetin is also being studied for its ability to reduce cell senescence. Its antioxidant and anti-inflammatory properties help to kill cancer cells, control blood sugar, and prevent heart disease.

Also under experimentation are suppression of human growth hormone (HGH), stem cell technologies that promise to prolong life indefinitely, and research into the genetic switches that control the biological processes of aging.

While much of this is wildly exciting, I think we should be hesitant to draw too many conclusions just yet from lab mice or flies about how humans should live.

Anyway, as some of these drugs are about to enter human trials, we’ll soon see what they produce. For the moment, however, the real control we have over the length of our life is at the personal level.

Does lifestyle matter?

There’s been a wide agreement for a long time as to the longevity benefits of a healthy lifestyle. More recent research digs into the specifics of those things in ways that are really interesting.

The research of Sinclair and others has shown that sirtuins respond well to caloric and amino acid restriction. Simply feeding mice 40% less in the lab extends their lives by as much as 30%. There’s also strong evidence that extending the length of time between feedings (known as intermittent fasting) yields even more dramatic benefits.

Equally dramatic, if a bit more complex, was the effect that protein restriction in a mouse’s diet (and thus amino acid restriction) had on longevity.

The rather new field of nutritional geometry has been offering new insights on this kind of research, exploring the relationship between food intake and longevity. There we find much good work being done on the benefits of restricted amino acid intake. Matthew Piper, for one, has offered interesting research on the way restricting amino acids lowers fertility while at the same time extending lifespan.

Another surprising finding was the benefit of keeping the body at a cold (and sometimes hot) temperature.

What has not yet entered the mainstream of biomedical research is something that’s been clear for centuries — that humans can live longer and healthier lives by slowing the rate of their breathing. People typically breathe 12-15 times per minute, though most breathe closer to 15.

A long yogic tradition in India and Tibet maintains that by reducing the breathing rate to 12 per minute, the average human lifespan of 82 years can be increased to 108 years. Reduce the rate to 9 per minute, and you lengthen life to 124 years. You get the idea.

We know that slowing the breath can slow the heartbeat, lower blood pressure, and reduce symptoms of stress, anxiety, and depression. While numerous medical studies have confirmed the extraordinary benefits, medical researchers continue to ignore them. Probably because it’s hard to control breathing in lab mice. And hard to create a startup around meditation and pranayama breathing practices (and also takes tremendous discipline).

Could COVID-19 adversely affect the lifespan of the human species?

We don’t yet know about the long-term effects of COVID on the human lifespan. Many questions are still ahead. We’ve already seen that for many of the individuals who die from the disease, life is shortened by 11-13 years or more.

But for all those who either recover or never know they’ve contracted it, we know little about the long-term effects of the disease on the body. As to what effect it might have on the longevity of the human species? Not yet clear.

It remains to be seen what the socioeconomic effects of the pandemic and its resulting economic shocks will be. As economies contract, will problems with the distribution of resources be prolonged? That could certainly affect human longevity.

So could the changes in our ability to be physically close to other people. Mental health is in some ways related to social connection and proximity. Lonely people tend to live shorter lives.

These issues will need to be addressed.

The long view

First of all, we need to consider what we’re after here. Is it death as a disease-to-be-cured, or is it aging well and healthy? Particularly given the COVID considerations, I’m focused on the latter of these.

If some of the focus, meaning, and passion of our lives derives from the limits of our mortality, I suspect those things could be compromised if our lives were to stretch 50% further. Bioethicist Leon Kass offers a very strong anti-anti-aging take: “To number our days is the condition for making them count.”

I think only a fool would choose to live forever. But for everyone to live a long, full life, with everything a human being could know, explore and experience in life, and then leave life quickly, would be a great blessing. Many individuals — indeed, perhaps most — suffer greatly from deterioration of health in the last years of their lives.

Assuming the additional years of extended life were healthy ones, a longer life could change a lot of things, creating tremendous opportunities for people.

It could also introduce economic challenges. But the global socioeconomic challenges expected with the current rapidly growing population of seniors (many of them with health challenges) can be easily expected to outweigh the challenges that result from more people living longer, healthier lives.

Back to the Austad/Olshansky debate. Olshansky’s expectation that we’re simply moving toward more years of health for everyone is based in part on our success in reducing the disparities between different socio-economic groups.

But the current political climate in the US and other parts of the world makes it hard to envision immediately what Olshansky anticipates.

I believe that the coming decade will be one of collaboration. That especially holds true for developments in the field of aging. To make longer-and-better-health-for-all possible, the world needs to collaborate. That includes more innovative governance, at both the national and the global level.

Researchers and entrepreneurs and citizens are all engaged around the topic of a longer, healthier life for more people. It’s now within reach. Biomedical research and technology continue to leap forward, and many citizens are already working with their doctors and providers as full participants in their own health care. What’s needed is for policymakers to come along, to make that possible for all.

The global population is older than ever before. But the disparity in lifespan between different demographics, countries, and contrasting life circumstances has also been growing. That has to change.

The biggest challenge right now lies not in the potential of medical technology — we know that’s exponential. But all stakeholders don’t seem to have the same goal. Biologists and biodemographers are not hanging out much with bioethicists, nor are biotech entrepreneurs with policymakers. To make progress that’s effective, comprehensive, and ethical, we need to work together.

We can get there.

Citizens, researchers, and biotech entrepreneurs will be pushing forward. If policymakers don’t come along willingly, I expect they’ll be dragged along by their constituents — kicking and screaming, if necessary.

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Camilla Warrender
Camilla Warrender

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