To Age or Not to Age

We’re at the dawn of another epoch of major discontinuous transformational shifts led by technology. One of the areas that I’ve been watching closely is in longevity and anti-aging, to both live longer and live younger, free from the ravages of aging related diseases and decline.

It’s another one of those domains that I believe is advancing more quickly than our ability to fully grasp and address the implications. Like AI, I believe anti-aging and longevity technology needs very careful navigation and a governing body of ethics and guardrails to ensure we don’t open a pandora’s box. There are many thorny issues, which I discuss in the tail end of the blog post.

I’ve informally canvassed family and colleagues “would you want to live a lot longer” and I’ve been somewhat surprised by the many who reject the desire to live “a lot” longer. Most believe there is a right time to bow out and that right time is below the age of 100. I haven't put a lot of thought into that question for myself but my hunch is that I enjoy living so much, I would never want my life to end.

A Look Back

The search for longevity and elixirs for youth have been an enduring quest throughout human history, spanning cultures, civilizations, and scientific advancements. From ancient folklore and mythical tales to contemporary scientific research, humans have always sought ways to extend their lifespan and unlock the secrets of immortality.

In ancient civilizations such as Egypt and China, the pursuit of longevity was intertwined with spiritual and philosophical beliefs. The Egyptians, for instance, believed in the concept of an afterlife and developed elaborate burial rituals to preserve the body for eternity. In China, the search for longevity was deeply rooted in Taoist philosophy, which emphasized the balance of yin and yang energies to achieve harmony and longevity. Practices such as meditation, herbal remedies, and alchemy were explored to attain immortality.

As human civilization progressed, scientific advancements and medical discoveries provided new avenues for understanding and pursuing longevity. During the Renaissance period, figures like Leonardo da Vinci and Paracelsus delved into alchemy and explored the concept of an elixir of life, a substance believed to grant immortality. However, these pursuits often remained speculative and lacked empirical evidence.

In the 20th century, advancements in biology, medicine, and genetics began to shed light on the mechanisms underlying aging and opened up new avenues for extending human lifespan. Scientific breakthroughs such as the discovery of DNA and the identification of telomeres, the protective caps at the ends of chromosomes, led to increased understanding of cellular aging processes.

All this yearning for living longer has worked. In the 19th century, global life expectancy was around 30 years. It is almost 73 years today (according to World Health Organization). But a sustained gradual increase in lifespan is one thing, a dramatic discontinuous increase is an altogether different thing.

Looking Ahead

In recent decades, research on longevity has become a multidisciplinary field, encompassing genetics, gerontology, nutrition, and lifestyle interventions. Scientists have identified various factors that influence lifespan, including genetics, epigenetics, caloric restriction, exercise, and environmental factors. Moreover, the identification of genes that regulate aging, such as the SIRT1 gene, has provided new targets for potential interventions.

Today, the search for longevity has become an enormous area of research, with scientists exploring cutting-edge technologies such as gene editing, stem cell therapies, and senolytics (drugs that target senescent cells, the “zombie” cells that no longer divide and sit around with damaged characteristics). Furthermore, advancements in artificial intelligence and machine learning are being employed to analyze vast amounts of data and gain insights into the complex interplay of factors influencing aging.

A study was recently published by one of the visible scientists in this domain, Dr. David Sinclair of Harvard, showing a lasting reset of cellular aging (my oversimplification) through a chemical cocktail intervention delivered over just four days. While the study has several limitations (as acknowledged by the researchers), it is nonetheless seminal and profound in that a reset of cellular aging was achieved in such a short period of time.

There are a number of areas of research that are showing potential:

• Senescence and Senolytics: cellular senescence refers to the state where cells lose their ability to divide and function properly, contributing to aging and age-related diseases. Senolytics are compounds designed to target and eliminate senescent cells. Research in this area aims to develop effective senolytic therapies to delay aging and promote healthier lifespans.
• Telomere Research: telomeres are protective caps at the ends of chromosomes, and their length is associated with aging and cellular health. Studies focus on understanding telomere dynamics and investigating the potential of telomerase activation to extend cellular lifespan.
• Caloric Restriction and Mimetics: caloric restriction has been shown to extend lifespan and delay age-related diseases in various organisms. Researchers are exploring caloric restriction mimetics—compounds that can mimic the beneficial effects of caloric restriction without actually reducing food intake—as a potential anti-aging strategy.
• Mitochondrial Health: mitochondria are essential organelles involved in energy production, and their dysfunction has been linked to aging. Investigating ways to maintain mitochondrial health and functionality is an important aspect of anti-aging research.
• Epigenetics: epigenetic changes influence gene expression without altering the DNA sequence. These changes play a role in aging and age-related diseases. Understanding and manipulating epigenetic modifications could provide insights into slowing down the aging process.
• Stem Cell Research: stem cells have the potential to regenerate damaged tissues and organs. Anti-aging research explores how stem cells can be utilized to repair age-related damage and rejuvenate tissues.
• Immunosenescence: the aging of the immune system, known as immunosenescence, leads to increased susceptibility to infections and age-related diseases. Research focuses on improving immune function in older individuals to promote healthy aging.
• Hormesis: hormesis is a biological phenomenon where exposure to mild stressors can trigger cellular repair mechanisms, resulting in improved resilience. Researchers investigate hormetic compounds and interventions that could enhance longevity and healthspan.
• Microbiome and Aging: the gut microbiome plays a crucial role in various aspects of health, and its composition changes with age. Research examines the relationship between the microbiome and aging, exploring potential interventions to modulate the microbiome for healthier aging.
• AI and Machine Learning: advanced data analytics, including AI and machine learning, are being used to analyze large datasets related to aging, genomics, and lifestyle factors. These approaches can identify patterns and correlations that might lead to novel anti-aging interventions.

The field of antiaging research has garnered significant attention and investment in recent years. According to a report by the global data provider CB Insights, venture capital funding in the antiaging sector reached over $2 billion in 2021. Notable investments have been made in areas such as biotechnology, regenerative medicine, genetics, and artificial intelligence. Major companies, as well as private investors and philanthropic organizations, are increasingly recognizing the potential of antiaging research and its implications for healthcare, longevity, and future economies. Some notable individual investors include Jeff Bezos, Sergey Brin, Larry Ellison, Peter Thiel and Jim Mellon.

This substantial financial support is expected to further propel scientific advancements and accelerate the development of innovative interventions and therapies targeting age-related conditions and promoting healthy aging.

Many forecasters in this field of study believe that in the next handful of years, we will identify breakthroughs that will allow humans to live to 125 years or beyond.?Simple caloric restriction studies alone have shown in mouse models to increase lifespan by as much as 40%.

Navigating the Perils

The pursuit of longevity and the potential to extend human lifespan raises several risks and ethical considerations. There are significant moral, philosophical and practical challenges.

First let’s start with the most glaring. As of 2021, according to Fidelity Investments, the average American household had $129K saved in their 401K. Social Security faces significant long-term funding challenges. So who’s going to pay for all of these people who are living 30 or 40 years longer? Will the technology only be available to those who can prove they have the financial means to live longer? Or will just shift the retirement age up 30 years? Will we shift it for everyone or just those who opt in to living 30 years longer?

Second, what’s the upper limit that we find acceptable and who gets to define it? What if immortality is possible? Should we pursue immortality. If yes why, if no why not?

Third, the possibility of overpopulation and social imbalances looms large if substantial life extension becomes a reality. The planet already houses 8 billion+ people and some have put the upper limit of stress on the planet at 10 billion. Will need global one child policies? Perhaps it won't matter because we will be immortal and that means we can become a cosmic interplanetary species.

Fourth, long-term safety issues and informed consent are critical to address for any experimental anti-aging interventions. It is very difficult to conduct long-term randomized trials to understand safety and efficacy. Will we accept evidence-informed in place of evidence-based?

Finally, defining aging and healthspan accurately, as well as grappling with existential concerns about identity and purpose in extended lifespans, also demand attention.

Balancing resource allocation, mitigating unintended consequences, and regulating the market will be essential for responsible progress in this complex and evolving field.

While the quest for immortality remains elusive, recent research has yielded significant advancements in our understanding of aging and the potential for extending healthy lifespan. From everything I've read, I believe we will see a discontinuous jump soon, in the next decade a technology or few will emerge than can meaningfully impact lifespan.?

But this is a complicated domain with many thorny challenges. I urge all of the scientists, entrepreneurs and policymakers working in this field to exercise our own moral and ethical instincts and give downside risk prevention some serious thought. The upside is clear and it's beautiful in my eyes.