Large-scale survey highlights challenges to advancing longevity research
The desire to extend human lifespan and promote healthier aging has evolved from a science fiction scenario to a tangible scientific goal. In recent years, advances in longevity research have fueled optimism that aging can be effectively combated in our lifetime. However, there are still significant hurdles to overcome on the way to this ambitious goal. Based on the findings of a survey of 400 experts conducted by the Longevity Biotech Fellowship Bottleneck Consortium here are five key components that are necessary to advance longevity research.
1. Refining biomarkers for aging
Accurate assessment of the effectiveness of anti-aging measures depends on reliable biomarkers of aging. Although DNA methylation is widely used, it does not cover the entire spectrum of age-related changes. The development of comprehensive biomarkers that reflect various aspects of aging independently of external factors is essential if the effectiveness of therapies is to be accurately assessed.
2. Increasing financial resources
Despite its potential to reduce the burden of age-related diseases, longevity research remains underfunded compared to disease-specific initiatives. Redirecting funds toward research into the underlying mechanisms of aging could yield significant health benefits. A balance between investment in disease-oriented research and research into the causes of aging is critical to maximizing long-term health outcomes.
3. Improved research models
Effective testing of anti-aging treatments requires accurate models that mimic the human aging process. Current models, such as animal experiments and cell cultures, can only replicate the complexity of human aging to a limited extent. In order to achieve progress in longevity research, more representative models need to be developed that better reflect human physiology and the diseases associated with aging.
4. Stricter regulatory framework
Conventional regulations for drug development are ill-suited to longevity therapies that target multiple age-related diseases simultaneously. The regulatory framework must therefore be adapted to allow therapies that target aging itself rather than specific diseases. This requires a reassessment of risk assessment methodologies and ethical considerations to facilitate the development and testing of anti-aging interventions.
5. Better public understanding
Despite increasing media coverage, there are still misconceptions about longevity research that undermine public support. It is therefore important to inform the public about the potential benefits of longevity research for general health and well-being in order to gain broader support and funding.
Raising public awareness, adapting regulations, improving research models, reallocating funding, and optimizing biomarkers will accelerate progress in longevity research. Successfully addressing these challenges can pave the way for a future in which healthier aging and longer life expectancy are not just aspired to, but achieved.
The challenges mentioned here do not cover all the problems identified by the Bottlenecks Consortium. Other frequently cited problems include insufficient data sharing between researchers and a lack of qualified professionals entering the field. The latter problem is partly linked to the aforementioned factors, such as funding constraints and regulatory barriers, which can discourage aspiring researchers from engaging in longevity research.
Detailed survey results and analyses with charts and infographics can be found on the Longevity Biotech Fellowship website.
Epigenetic changes are a cause of aging
A study shows that manipulating the epigenome can accelerate and reverse aging
According to the theory of aging information, our genome is comparable to biological hardware, while the epigenome is software—and aging is a software problem that can be fixed by restarting from a backup copy.
An international study, which took 13 years to complete, shows for the first time that deterioration in the way DNA is organized and regulated—known as epigenetics—can accelerate the aging of an organism independently of changes in the genetic code itself.
The researchers triggered accelerated aging in mice by causing DNA breaks that trigger a cellular repair process and changes in DNA organization, i.e., epigenetic changes. The authors demonstrated that it was the increased stress caused by DNA reorganization and the resulting loss of epigenetic information, rather than changes in the DNA sequence, that caused the mice to age faster.
Using gene therapy, they then introduced factors into the mice that partially restored the integrity of the epigenome and returned the organs and tissues to a youthful state, allowing aging to “advance and reverse at will.”
“We believe our study is the first to demonstrate that epigenetic changes are the primary cause of aging in mammals,” said the study’s lead author, David Sinclair, professor of genetics at the Blavatnik Institute at Harvard Medical School and co-director of the Paul F. Glenn Center for Biology of Aging Research.
The epigenetic reset led to improved aging markers in the kidneys, muscles, and eyes. While the study is significant, other scientists in the field caution that without further experimentation, it is too early to draw major conclusions about the nature of aging and our ability to reverse it.
Leonard Guarente, American biologist, Novartis Professor of Biology, and director of the Paul F. Glenn Center for Biology of Aging Research at MIT (Massachusetts Institute of Technology), Boston, has this to say:
“Studies on yeast and mammalian cells over the past 25 years have shown that DNA double-strand breaks cause a redistribution of epigenetic regulators that affect histone acetylation and methylation throughout the genome, which could be a cause of aging. This paper describes how a small number of genomic DNA breaks can be induced in young mice and how the effects are observed during aging. The results indeed show a redistribution of epigenetic markers throughout the genome and accelerated biological aging as measured by epigenetic DNA methylation clocks, as well as canonical aging phenotypes in animals. These epigenetic changes can be partially reversed by the expression of Yamanaka factors. The results support a model in which DNA breaks and the resulting changes in the epigenetic landscape are important causes of normal mammalian aging.”
Guarente is best known for his research on lifespan extension in Saccharomyces cerevisiae yeast, roundworms, and mice.
References
Yang, J. H., Hayano, M., Griffin, P. T., Amorim, J. A., Bonkowski, M. S., Apostolides, J. K., Salfati, E. L., Blanchette, M., Munding, E. M., Bhakta, M., Chew, Y. C., Guo, W., Yang, X., Maybury-Lewis, S., Tian, X., Ross, J. M., Coppotelli, G., Meer, M. V., Rogers-Hammond, R., . . . Sinclair, D. A. (2023). Loss of epigenetic information as a cause of mammalian aging. Cell, 186(2), 305-326.e27. https://doi.org/10.1016/j.cell.2022.12.027