Unlocking the biology of aging

What we know and where the industry seems to be heading.

For most of human history, aging was seen as an inevitable process. But as science advances, some are beginning to ask: what if aging itself is treatable? What if we could slow it down, or even reverse some aspects of it? These questions have fueled a surge in longevity research and biotech investment. But how much of this is hype, and how much is grounded in biology?

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Over the past century, global life expectancy has seen a remarkable increase. In 1900, the average life expectancy at birth was approximately 32 years. By 2021, this figure had more than doubled, reaching 71 years (Our World in Data). A significant factor contributing to this rise is the substantial reduction in child mortality rates. In 1990, the global under-five mortality rate was 93 deaths per 1,000 live births. By 2022, this rate had declined by 60%, dropping to 37 deaths per 1,000 live births (UNICEF).

But preventing childhood deaths does not explain the full picture. Improved sanitation, access to antibiotics, advances in surgical techniques, and a better understanding of nutrition and chronic disease prevention have all played critical roles in keeping people alive longer. Today, reaching old age is no longer an exception but the norm.

From Our World in Data

Yet, while people are living longer, many of those years come with an increasing burden of chronic disease. Cancer, cardiovascular disease, and neurodegeneration have replaced infections as the primary causes of mortality. These conditions are not new, but in the past, fewer people lived long enough to develop them. Now, instead of facing a single life-threatening illness early on, older folks often spend decades managing multiple, complex health conditions.

This shift raises an important question: if aging itself is the biggest risk factor for these diseases, could targeting the aging process directly help us stay healthier for longer?

Just like most (maybe all?) things in biology, aging is complicated and is not a single, uniform process. Over the past few decades, researchers have identified some of the key molecular and cellular mechanisms that drive aging like the accumulation of DNA damage and changes in mitochondrial function and cellular senescence. In animal models, interventions that modify these pathways have extended lifespan and delayed age related decline but translating these discoveries into real human therapies remains an open challenge.

Now, a growing number of biotech startups are stepping into the field, aiming to translate scientific discoveries into real-world treatments. Companies like Retro Biosciences and NewLimit suggest that aging is not an inevitable process but one that can, at least in part, be influenced. However, whether these approaches will truly work remains an open question—one that will take time and rigorous testing to answer. So, what do we actually understand about the biology of aging, and what key uncertainties still remain?

The Molecular Biology of Aging: What We Know So Far

Aging is not a single event but a gradual breakdown of biological systems. Several key molecular processes have been shown to contribute to this decline. These interconnected mechanisms, often referred to as the hallmarks of aging, help explain how cells lose function over time and why aging is the biggest risk factor for diseases such as cancer, neurodegeneration, and metabolic disorders.

At its core, aging is a complex interplay of damage accumulation, loss of cellular maintenance, and changes in gene regulation. While the exact triggers are still debated, researchers have identified several key biological processes that drive aging at the molecular level:

• Genomic Instability – Over time, DNA accumulates damage from environmental stressors, metabolic byproducts, and replication errors. These mutations and chromosomal abnormalities can impair cellular function and increase the risk of diseases like cancer (López-Otín et al., 2013).

• Epigenetic Alterations – Cells rely on intricate regulatory mechanisms to control gene expression, but with age, these processes become dysregulated. Changes in DNA methylation, histone modifications, and chromatin structure can disrupt normal gene function, leading to loss of cellular identity and an increased susceptibility to age-related diseases (Horvath, 2013).

• Mitochondrial Dysfunction – Mitochondria, the cell’s energy powerhouses, gradually lose efficiency with age. This decline results in reduced ATP production and heightened oxidative stress, which damages proteins, lipids, and DNA, further accelerating cellular aging (Bratic & Larsson, 2013).

• Cellular Senescence and Chronic Inflammation – When cells experience excessive damage, they stop dividing and enter a senescent state. While this can prevent uncontrolled cell growth and cancer, senescent cells do not simply disappear—they linger, secreting inflammatory molecules that impair tissue function and contribute to chronic diseases (Tchkonia et al., 2013).

• Loss of Proteostasis – Proteins must be properly folded and maintained for cells to function correctly, but aging disrupts this balance. Misfolded and aggregated proteins accumulate, which is a hallmark of neurodegenerative disorders such as Alzheimer’s and Parkinson’s (Hipp, Park, & Hartl, 2014).

The Hallmarks of Aging

Can We Actually Intervene in Aging?

The idea of targeting aging itself—rather than just managing the diseases it causes—has gained significant momentum in recent years. Instead of focusing solely on treatments for cancer, cardiovascular disease, or neurodegeneration, researchers are exploring whether aging can be slowed, delayed, or even reversed.

So far, most experimental interventions have been studied primarily in animal models where some of the most widely discussed approaches include:

• Parabiosis – Infusing old mice with young blood has been shown to rejuvenate brain function and improve tissue health. This effect, first observed decades ago, has gained renewed attention as researchers try to pinpoint which factors in young blood drive these benefits (Pálovics et al., 2022).

• Rapamycin – Originally developed as an immunosuppressant, rapamycin has emerged as one of the most robust lifespan-extending compounds in animal models. Mice treated with the drug live 20–30% longer, likely due to its role in inhibiting mTOR, a cellular pathway linked to aging and metabolism (Harrison et al., 2009).

• Cellular Reprogramming – Yamanaka factors, a set of genes that can reset cells to a more youthful state, have been shown to reverse some signs of aging in mice. However, fully reprogramming cells can also lead to uncontrolled growth, raising concerns about cancer risk (Ocampo et al., 2016). A graphical abstract for this study is shown below.

Graphical abstract from “In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming, Cell 2016”

Antibodies as an Anti-Aging Strategy

One of the most intriguing recent developments in longevity research is the use of antibodies to target aging-related pathways. In July 2024, researchers discovered that blocking a protein called IL-11 using specific antibodies could reduce inflammation and extend mouse lifespan by 25% (Nature, 2024).

IL-11 is a cytokine linked to chronic inflammation, a key driver of many age-related diseases. As cells age, they produce inflammatory molecules that contribute to tissue damage and dysfunction. By neutralizing IL-11, researchers observed improved tissue function and increased longevity in mice. If these findings translate to humans, antibody-based therapies could become a powerful tool to combat damaging levels of inflammation.

But as with all aging research, there is a crucial caveat: what works in mice does not always work in humans. Many promising anti-aging interventions have failed in clinical trials or shown unintended side effects. The challenge is not just identifying a mechanism that influences aging but determining whether it can be safely and effectively modified in people without introducing new risks.

As research progresses, antibodies and other biologics may become a viable strategy for targeting aging-related inflammation. But for now, the question remains: are we on the cusp of real longevity breakthroughs, or are we still in the early stages of understanding how to translate these findings into meaningful human health benefits This uncertainty however, has not stopped biotech startups from jumping in with ambitious claims and massive investments, promising to turn experimental discoveries into real-world treatments.

The Billion-Dollar Longevity Bet: Boom or Bust?

Despite being in its early stages, aging research is attracting significant investment, with biotech startups moving quickly to commercialize potential interventions. Two of the most talked-about companies in this space are Retro Biosciences and NewLimit, both backed by Silicon Valley billionaires who see aging as a biological process that can be engineered.

Retro Biosciences: The $180M Bet on Extending Human Life

Funded in part by OpenAI CEO Sam Altman, Retro Biosciences is taking a multi-pronged approach to longevity, focusing on:

• Plasma Dilution Therapy – Inspired by parabiosis studies, Retro is investigating whether filtering out harmful factors from aging blood can restore youthful function.

• Cellular Reprogramming – Using Yamanaka factors to rejuvenate aging cells, aiming to reset them to a more youthful state without triggering uncontrolled growth.

• Autophagy Enhancement – Boosting the body's ability to clear out damaged cells and misfolded proteins, which accumulate with age.

Retro has not yet published detailed findings, and much of its work remains under wraps. However, its funding and ambitious focus suggest it could play a major role in shaping the future of longevity research.

NewLimit: Reprogramming Aging at the Epigenetic Level

Co-founded by Coinbase CEO Brian Armstrong, NewLimit is taking a more specific approach, betting that epigenetic reprogramming or resetting cellular identity will slow or reverse aging. What does that actually mean?

As cells age, their epigenetic landscape (the chemical modifications on DNA that regulate gene expression) becomes altered. This disrupts normal gene function, leading to cellular decline. The hope is that by resetting these markers, aging cells will regain their youthful function.

NewLimit’s primary goals are to:

• Reverse age-related epigenetic changes in human cells.

• Restore youthful function to aging tissues.

• Develop safe reprogramming methods without increasing cancer risk (that’s a big one).

The idea is compelling, but there are major challenges just as with Retro’s approach:

• How do you reprogram cells without increasing cancer risk?

• Even if we reset epigenetic markers, will that actually rejuvenate tissues?

• How do we test this safely in humans?

So far, NewLimit’s work is entirely experimental, with little public data showing whether this approach will work outside of a petri dish. The company is asking big questions, but whether it can deliver meaningful results remains to be seen.

Epigenetic regulation is at the nexus of ageing rejuvenation ncRNA non-coding RNA; RE, Repetitive elements.

Is this hype a hit or a myth?

The enthusiasm around longevity biotech is undeniable, but there is also a reality check: the most proven ways to extend healthspan may not require billion-dollar startups. They require investment in preventive medicine, public health, and lifestyle interventions, strategies that already have strong evidence behind them but are often underfunded.

For example:

• Alzheimer’s disease – Research shows that exercise, diet, and better cardiovascular health significantly lower dementia risk. Would we be better off focusing on broad public health interventions rather than high-risk biotech ventures?

• Cancer prevention – Early detection and screening programs save lives. Should we be investing more in expanding access to proven diagnostics rather than hoping for a future aging "cure"?

The dream of dramatically extending human lifespan is exciting, but it is important to remember that aging research is still in its early days. While these biotech companies may one day make groundbreaking discoveries, the most effective longevity strategies available today are not experimental gene therapies or magic pills. They are the same foundational habits doctors have been recommending for decades: regular exercise, a balanced diet, clean air, and reducing environmental risk factors for chronic disease.

That may not sound as futuristic as 'hacking aging,' but for now, it remains our best bet for a longer, healthier life. That said, I find this field fascinating, and I am eager to see where it leads and maybe even be a part of that journey as a scientist myself. The complexity of aging biology makes it one of the most intriguing challenges in science, and dedicating resources to understanding it—both in the lab and in the clinic—will undoubtedly shape the future of medicine.

In the coming weeks, I will be diving deeper into aging research, exploring the key mechanisms that drive it, and highlighting the many open questions that remain. I will also share insights from my own PhD work in the context of aging science and discuss what I find most exciting about the future of this field.

Let me know your thoughts - what do you think is the most promising avenue of aging research? I would love to hear your perspective.

- Karin

Acknowledgments:

• Phil Fradkin (https://philechka.com/) for valuable discussions and suggestions.