The UN’s Brief on the Biology of Aging

Key Points:

• In the brief, the UN’s Scientific Advisory Board defines aging as a decline in physiological function, a reduced capacity to recover from stress, and an increased susceptibility to disease and death.
• To combat aging, the interdisciplinary field of geroscience has been developed, which seeks to delay, prevent, and treat multiple diseases linked to aging processes.
• The UN Scientific Advisory Board highlights recent breakthroughs in geroscience, including gene therapy, which involves replacing faulty genetic sequences.

Aging is an inevitable part of life, a complex process that affects every living organism. For centuries, humanity has been fascinated by the prospect of extending lifespan and maintaining vitality into old age. While the fountain of youth remains a mythical concept, groundbreaking scientific advancements are shedding new light on the biological mechanisms of aging, offering unprecedented opportunities to not only potentially extend life but to enhance the quality of those extended years. This article, drawing insights from a recent brief by the UN Scientific Advisory Board, delves into the fascinating world of geroscience—the interdisciplinary field dedicated to understanding and combating the aging process.

What is Aging?

In biological terms, aging is characterized by a decline in function, a reduced capacity to recover from stress, and an increased susceptibility to disease and death over time. It is a multifaceted process influenced by a combination of genetic, environmental, and social factors, manifesting uniquely in each individual.

The UN Scientific Advisory Board’s brief highlights several key biological hallmarks of aging:

Molecular and Cellular Processes

At the core of aging lies the accumulation of damage at the molecular and cellular level. Our cells, over time, undergo a process called “senescence,” where they gradually lose their ability to replicate and function properly. This cellular decline is often driven by:

• DNA Mutations and Damage: Our genetic material is constantly under assault from various stressors, leading to mutations and damage. While our bodies have repair mechanisms, their efficiency declines with age, contributing to genomic instability.
• Telomere Shortening: Telomeres are protective caps at the ends of our chromosomes. With each cell division, these telomeres shorten. Once they become too short, cells can no longer divide and enter senescence. Telomere dysfunction is a significant contributor to cellular aging.
• Loss of Proteostasis: Proteostasis refers to the ability of proteins to maintain their quality and proper folding. As we age, this ability can decline, leading to the accumulation of misfolded proteins, which can contribute to various disorders, including neurodegenerative diseases like Alzheimer’s.

Genetics and Epigenetics

Our genes play a crucial role in determining our susceptibility to diseases and our overall aging trajectory. While some genetic predispositions can increase the risk of age-related diseases like cancer and heart attacks, the field of epigenetics offers a more nuanced understanding. Epigenetics refers to changes in gene expression that do not involve alterations to the underlying DNA sequence. These epigenetic modifications, such as DNA methylation and histone modifications, can deteriorate with aging, influencing our biological age and mortality risk. Large-scale genome studies have even identified specific genetic variations, like those in the apolipoprotein gene, that are strongly linked to longevity and can influence the risk of diseases like Alzheimer’s.

Systemic Biomarkers

Beyond the cellular level, aging can be observed through the functional decline of tissues and organs. Blood-based biomarkers, such as glucose and cholesterol levels, are well-established indicators of physiological aging, correlating strongly with disease and mortality. Changes in metabolic functions, hormone production, and organ degeneration are all recognized markers of the aging process.

Inflammation and the Immune System

Chronic, low-grade inflammation, often referred to as “inflammaging,” is a hallmark of aging. This persistent inflammation arises from factors like cellular senescence, oxidative stress, and the accumulation of molecular damage. Inflammaging contributes to a wide range of age-related conditions, including degenerative disorders, cardiovascular disease, and various cancers. Furthermore, the immune system’s effectiveness wanes with age, making older individuals more vulnerable to infections and diseases.

These interconnected processes provide a comprehensive understanding of how aging manifests at different biological levels, laying the groundwork for targeted interventions to promote healthier and longer lives.

What is Geroscience?

Geroscience is an emerging interdisciplinary field that seeks to understand the fundamental biological mechanisms of aging and their contributions to age-related diseases. The ultimate goal of geroscience is to develop interventions that can delay, prevent, or treat multiple disorders and diseases linked to these aging processes, thereby extending not just lifespan, but also healthspan—the period of life spent without age-related chronic conditions.

The field of geroscience encompasses several key approaches:

• Altering or Tracking Biological Mechanisms: This involves identifying and manipulating the core biological processes that drive aging, such as those related to DNA repair, cellular senescence, and metabolism.
• Pharmacological Treatments: Developing drugs that target age-related diseases, with the aim of slowing or reversing the aging process itself.
• Dietary Interventions: Investigating how specific dietary approaches can improve healthspan and prevent age-related dysfunction.
• Surgical Approaches and Regenerative Medicine: Exploring advanced techniques like organ replacement, bionic augmentation, and tissue regeneration to address age-related decline.

Geroscience has moved beyond simply studying aging as a natural decline; it views aging as a malleable process that can be influenced through scientific intervention. This shift in perspective has opened new avenues for research, including the potential for gene editing and other pharmacological manipulations to delay aging.

Recent Developments and Breakthroughs

Over the past 25 years, significant advancements in genetics have fueled optimism that human aging processes could potentially be slowed or even suspended. Discoveries related to longevity genes, enzymes involved in DNA repair, and the effects of dietary interventions have led some scientists to believe that aging is at least partially biologically controllable. This optimism has spurred massive investments in gerontology research, though some critics caution against overly optimistic expectations not yet supported by widespread application.

Key developments highlighted by experts in the field include:

• Epigenetic Reprogramming: As cells and DNA age, they lose genetic and epigenetic information, leading to changes in gene expression. Recent studies, particularly in animal trials, suggest that this loss of information might be reversible, opening doors for new therapeutic approaches to age-related diseases and extended healthspans.
• Base Editing: Inspired by the success of CRISPR gene-editing, base editing techniques have shown promise in correcting genetic mutations responsible for rapid aging symptoms, such as those seen in Hutchinson-Gilford progeria syndrome. While still in early stages, this technology holds potential for pinpointing and eradicating significant age-related diseases. However, recent findings suggest that the aging process might be more complex than previously thought, involving a cascade of genetic changes that could make broad genetic modifications more challenging.

Despite these exciting findings, the biology of aging remains a fundamental mystery. Theories abound, and new discoveries are constantly emerging, but a universally accepted concept of aging has yet to materialize. The accelerating progress in artificial intelligence (AI) is expected to play a crucial role in geroscience, particularly in making sense of the vast amounts of data generated by aging research.

Considerations

Geroscience has profound implications that extend beyond the health sector, impacting global economies and sustainable development goals. Some critical considerations include:

Social and Economic Burdens

While extending human lifespans is a noble goal, it could lead to a larger, older population, potentially straining social and health systems and impacting economic growth. The economic benefits of targeting aging and extending healthspans are potentially enormous, but only if increased longevity is accompanied by preserved function and improved healthspans. The scientific community is increasingly advocating for balanced approaches that prioritize healthspan, prevention, and a care economy for aging populations.

Inequalities

The majority of geroscience research is currently concentrated in the Global North, with significant investments from large companies targeting affluent populations. This trend risks exacerbating global health inequalities, as emerging therapies and treatments may only be accessible in developed regions or tailored to specific demographics. Equitable development of geroscience, reduced barriers to access, and capacity-building in the Global South are crucial for navigating future demographic transitions. Furthermore, there’s a recognized need to address gender bias in health research, ensuring that geroscience accounts for gender-specific aging pathways.

Dual-Use of Geroscience

Like many scientific advancements, geroscience carries potential dual-use risks. Therapies designed to combat fatigue or enhance cognitive abilities could theoretically be misused, for instance, to create more resilient soldiers. Conversely, treatments to reverse or slow aging could be manipulated to accelerate aging or induce diseases. While these scenarios are currently speculative, there is a growing call for scientific forums and normative safeguards to ensure the safe and ethical development of geroscience.

Conclusion

The field of geroscience is rapidly advancing, offering exciting prospects for understanding and intervening in the aging process. By unraveling the complex biological mechanisms that drive aging, scientists are paving the way for a future where extended healthspans and improved quality of life are within reach. However, as with any transformative scientific endeavor, it is crucial to address the ethical, social, and economic implications to ensure that the benefits of geroscience are equitably distributed and responsibly applied for the betterment of all humanity.