The Science to Fix Aging

Aging is the leading cause of suffering and death worldwide. Every day, over 100,000 people die from age-related diseases such as cancer, Alzheimer's, and heart disease. This is because advanced biological age – essentially the accumulation of damage in our cells and tissues – is the biggest risk factor for these diseases. Traditional medicine usually addresses each age-related disease after it appears, and classic gerontology efforts try to slow down the damage accumulation by tweaking metabolism or lifestyle. In contrast, the damage repair approach aims to directly repair the underlying cellular and molecular damage of aging before it causes disease. By fixing the damage that builds up with age, scientists believe we can prevent or even reverse age-related diseases, effectively rejuvenating the body and extending healthy lifespan.

Aging as Damage Accumulation (and a Curable Condition)

According to this approach, aging is essentially seen as a side-effect of normal metabolism – a lifelong accumulation of various forms of damage in the body's cells and tissues. Once the damage passes a certain threshold, it leads to pathology: the familiar diseases and frailty of old age. However, if we periodically repair this damage at the molecular and cellular level, we could reset the biological clock, restoring tissues to a younger state and preventing those diseases from ever arising. After such rejuvenation treatment, damage would slowly begin accumulating again with time – but the key idea is that rejuvenation therapies could be applied repeatedly at intervals to keep damage below the harmful level. In this scenario, people might indefinitely retain the health and vigor of young adults, essentially curing aging as we know it.

Crucially, the damage-repair strategy is considered easier to implement than trying to slow aging by re-engineering metabolism. Metabolism is extraordinarily complex – intervening in it can cause many unintended side-effects because of how interdependent biological pathways are. Repairing damage after it occurs, on the other hand, is more straightforward: one doesn't need to grasp every nuance of metabolism to undo its by-products. Instead, researchers can identify the various forms of damage that are known to occur and develop targeted therapies to remove or neutralize each of them. In other words, rather than trying to change the incredibly complicated machinery of the body (which could cause new problems), the focus is on periodically cleaning up and fixing the "wear and tear" that the machinery produces. This approach takes advantage of the fact that scientists already know a great deal about the types of damage involved in aging.

SENS and the Hallmarks of Aging: One Unified Framework

Over the past two decades, biogerontologists have converged on this damage-centric view of aging. Two prominent frameworks encapsulate it: Strategies for Engineered Negligible Senescence (SENS) and the Hallmarks of Aging. Importantly, these are not competing or opposite theories – they are fundamentally the same concept: both describe aging as resulting from a handful of core damage processes and advocate repairing that damage to fight aging. The difference between them lies only in how they categorize the damage. SENS, first articulated by Dr. Aubrey de Grey in the early 2000s, groups all aging damage into seven broad categories for which repair strategies are envisioned. The Hallmarks of Aging framework, proposed in a 2013 Cell paper by López-Otín et al., describes essentially the same phenomena but breaks them into a different number of categories (originally nine hallmarks, updated to twelve in 2023). In principle, however, both frameworks point to the same underlying idea: aging is driven by accumulated damage, and by addressing each category of damage, we can effectively treat aging itself.

It's worth noting how influential this perspective has become. The Hallmarks of Aging publication (2013) became the most highly cited paper in the aging research field in the last decade. It provided a common language for researchers by clearly defining the major types of biological damage that come with age, which in turn has guided countless studies and new therapies aimed at those damage processes. SENS explicitly frames aging as an engineering problem to be solved and calls for immediate development of rejuvenation biotechnologies. Both frameworks continue to shape anti-aging research, reinforcing each other and driving the field toward interventions that repair the root causes of aging instead of merely treating its symptoms.

The Seven Categories of Damage (SENS)

The SENS model enumerates seven categories of cellular and molecular damage that encompass all age-related degeneration. These seven types of damage are: Cell loss and atrophy, Division-obsessed cells, Death-resistant cells, Mitochondrial mutations, Intracellular junk, Extracellular junk, and Extracellular matrix stiffening.

• Cell loss and tissue atrophy – Cells die and are not automatically replaced, leading to tissues that thin out or weaken with age. (Solution: stimulate regeneration via stem cells or growth factors.)
• Division-obsessed cells – Also known as uncontrolled cell proliferation, this is essentially cancer: cells that keep dividing when they shouldn't. (Solution: novel cancer therapies.)
• Death-resistant cells – Cells that should die (for example, worn-out or dysfunctional cells) but don't, often called senescent cells, which then linger and secrete harmful signals. (Solution: remove or reprogram these cells, for instance with senolytic drugs or immune therapies.)
• Mitochondrial mutations – Damage to the mitochondrial DNA inside cells, which impairs energy production and can contribute to aging. (Solution: protect or restore mitochondria, e.g. by moving critical mitochondrial genes to the cell nucleus or other gene therapies.)
• Intracellular junk – The accumulation of junk proteins or aggregates inside cells (such as misfolded proteins or resistant metabolic by-products like lipofuscin) that the cell cannot break down. (Solution: introduce novel enzymes or enhanced recycling mechanisms to clear out these wastes.)
• Extracellular junk – Harmful aggregates outside cells, in the spaces between cells. A key example is the amyloid-beta plaques that contribute to Alzheimer's disease. (Solution: immunotherapy or other means to dissolve or remove these extracellular deposits.)
• Extracellular matrix stiffening – Structural proteins in the extracellular matrix (like collagen) can form cross-links or other alterations over time, making tissues stiffer and less functional (this contributes to wrinkles, arteriosclerosis, etc.). (Solution: break the cross-links with drugs or enzymes, restoring elasticity.)

These categories cover the "damage map" of aging. Notably, no new fundamental type of age-related damage has been discovered outside these categories for decades, suggesting that this list is comprehensive. The Hallmarks of Aging describe a very similar set of phenomena in different words – for instance, several Hallmarks (genomic instability, telomere attrition, loss of proteostasis, etc.) correspond to one or another SENS category – but both frameworks are mapping the same problem of accumulated damage. In both cases, the end goal is to develop a suite of therapies that, collectively, repair all of these damage types in a person.

From Theory to Practice: Prospects for Rejuvenation

The damage repair approach is no longer theoretical; it is already shaping real interventions. Numerous start-ups, biotech companies, and research institutes are pursuing therapies that target various Hallmarks of Aging/damage categories – for example, senolytic drugs to clear senescent (death-resistant) cells, enzyme therapies to break down protein aggregates, gene therapies to fix mitochondrial mutations, and so on. This shift in focus from "treating diseases" to treating aging itself has been a dramatic change in biomedicine. It has been facilitated by the success of the Hallmarks framework in rallying scientific interest and by early proof-of-concept demonstrations (such as clearing senescent cells in mice to reverse aspects of aging). Still, the approach is in its infancy. At present, only a small fraction of the potential damage-repair interventions are even in early development. The current research funding and effort in this area is only a tiny fraction of what is needed to tackle aging comprehensively, according to proponents of the field.

Advocates argue that no fundamentally new scientific breakthrough is required to cure aging – we largely know what needs to be fixed. Every type of age-related damage seems to be already identified, and at least in principle, strategies exist to repair each of them. In the words of the SENS researchers, it's now an engineering challenge: implementing all these solutions and making them safe and effective in humans. Aubrey de Grey and colleagues have often likened this to maintaining a complex machine: if you can periodically remove the rust and replace worn-out parts, the machine can keep running indefinitely. The roadmap for doing this to the human body is conceptually clear – what's needed is concerted action and resources. The science itself is on a "relatively clear road," and the main barriers are now funding and logistics, not knowledge. If many more researchers and vastly greater funds were devoted to the damage-repair approach, progress would greatly accelerate.

In fact, experts in this field believe that with sufficient support, we could see working rejuvenation therapies in the not-distant future. One projection is that robust rejuvenation in laboratory mice could be achieved in about 10 years, and the first wave of human rejuvenation treatments could follow a decade thereafter – if the research is very well funded and efficiently executed. In other words, on the timescale of 10–20 years, we might develop the medical tools to fundamentally reset aging in humans, not just slow it. This optimistic scenario assumes a Manhattan Project-like effort: thousands of research groups each tackling a different piece of the aging puzzle in parallel, so that all categories of damage get addressed around the same time. With our current, more modest efforts, it will take longer; however, even now the trend is clear. Each year, new therapies targeting aging damage are entering clinical trials (for example, senolytics for senescent cells and immunotherapies for amyloid plaques are already in human testing). As these partial rejuvenation therapies emerge, they will likely prove the concept and attract further investment, creating a virtuous cycle.

In summary, the damage repair approach to aging – as exemplified by SENS and the Hallmarks of Aging – offers a promising path to end age-related disease and extend healthy life. Rather than viewing aging as an untouchable natural process, it reframes it as a set of concrete biological problems that can be solved with tools of medicine and biotechnology. By dividing aging into its component damages and conquering each one, scientists aim to prevent the entire cascade of degeneration that we now consider "getting old." This paradigm has gained tremendous traction in the scientific community, and if its potential is realized, the implications for human health and longevity would be revolutionary. Aging, in this new view, becomes not an inevitable fate but a challenge we can overcome – possibly within our lifetimes – through applied science and engineering of the human body's maintenance processes. The hallmarks may vary in number or name, but the message is the same: to cure aging, find the damage and fix it. With sustained research efforts, adequate funding, and continued advances, the once "impossible" dream of curing aging may well become a practical reality.