Academy Member Wang Xiaodong Showcases Anti-Aging Breakthrough: Mice Achieve 'Biological Immortality'—Is Human Aging Delay Within Reach?

In May, the “2023 HongShan Global Healthcare Industry Summit” was held at the Zhangjiang Science Hall in Shanghai. Themed “Begin with the End in Mind, Reach Far by Attending to the Minute,” the summit featured keynote presentations ranging from scientific breakthroughs in frontier healthcare to concrete application scenarios and solutions for translating technological innovations into practice. It systematically dissected “unmet needs” in the healthcare sector, covering a broad spectrum of hot topics of common interest to academia, industry, and the investment community, thereby fostering effective and in-depth exchanges.

At the conference, Dr. Wang Xiaodong, Academician and Director of the National Institute of Biological Sciences, Beijing, delivered a presentation titled “Pathways Available to Humans in Combating Aging.” He shared the scientific mechanisms underlying aging and approaches to anti-aging, providing evidence that the aging process is determined by the interactions among an individual’s genes, proteins, and environment. VCBeat has compiled and edited the highlights from his insightful presentation.

Wang Xiaodong is a Foreign Member of the Chinese Academy of Sciences, Director of the National Institute of Biological Sciences in Beijing, and a co-founder of BeiGene. In 2004, Dr. Wang was elected as a Member of the U.S. National Academy of Sciences. In 2014, he was elected as a Foreign Member of the European Molecular Biology Organization (EMBO) and has received numerous international awards for biological research. His research focuses on the biochemical pathways and processes of apoptosis. He has published many academic papers in prestigious international journals such as Science and Nature, establishing himself as a renowned scholar in this field globally.

Results from China’s Seventh National Population Census show that the population aged 60 and above has exceeded 260 million, accounting for 18.70% of the total, an increase of 5.44 percentage points compared with 2010. As China accelerates into an aging society at an unprecedented pace, the importance of studying aging in modern society is self-evident.

How Can Aging Be Delayed? Academician Wang Xiaodong Suggests That Pharmaceuticals May Offer a Solution. By understanding at the molecular and mechanistic levels how genes, proteins, and environmental factors determine the aging process, we can employ various technologies to intervene in this process, thereby achieving delayed aging and even healthy aging.

Academician Wang Xiaodong first explained the scientific mechanisms underlying aging. Human life comprises distinct stages, including development, growth, maturity, and aging. Throughout these stages, the body undergoes various changes. The aging process is genetically controlled; different species possess distinct genetic profiles, resulting in varying lifespans. Furthermore, gene-environment interactions significantly influence longevity.

In the animal kingdom, the lifespans of various species are limited, and these limits vary. Taking a relatively narrow taxonomic group as an example, the naked mole-rat is a subterranean animal that lives in darkness. Its genetics and growth environment enable it to live significantly longer than its counterparts. While typical rodents, such as rabbits and mice, have lifespans of only a few years, naked mole-rats can live for 40 to 50 years.

Another more specific animal is Brandt’s bat, a species of bat. This bat carries a mutation in the IGF (insulin-like growth factor) gene that significantly extends its lifespan. This indicates that although lifespan is genetically controlled, if it is regulated by a multidimensional matrix of genes, it may take decades to fully understand the role of each genetic node in the aging process.

Naked mole rats and Brandt’s bats are both mammals. Additionally, a simpler model organism has taken the lead in longevity research—the nematode *Caenorhabditis elegans* (*C. elegans*). This organism is remarkably simple, nearly invisible to the naked eye, with cells observable only under a microscope. It has a lifespan of just a few weeks and is transparent throughout its body.

Caenorhabditis elegans has made groundbreaking contributions to the field of aging research. Cynthia Kenyon, an American scientist who has long studied the mysteries of lifespan, discovered a single-gene mutation that doubles the lifespan of C. elegans. This study advanced the understanding of aging from descriptive and phenomenological observations directly to the genetic and molecular levels.

Academician Wang Xiaodong stated that, through years of research, a series of approaches have now emerged in the field of anti-aging.

First, we focus on the body’s energy factories—the mitochondria.Mitochondria function as energy-providing boilers, generating power for the body by metabolizing ingested food. However, this metabolic process produces factors that can damage mitochondria and even cells. This phenomenon reflects a prominent theory of aging: mitochondrial damage contributes to organismal aging.

The second approach is to clear senescent cells.In human tissues, particularly in non-dividing tissues such as nerves and muscles, the accumulation of senescent cells can trigger various inflammatory responses, thereby accelerating aging. Therefore, the clearance of senescent cells is currently being investigated as a strategy in the field of anti-aging research.

Third is stem cell therapy.Research on stem cells has made rapid progress over the past two decades. Individuals can now generate induced pluripotent or even totipotent stem cells, as well as tissue-specific stem cells such as those for skin, intestine, lung, and muscle. In the field of aging research, there is significant interest in whether stem cell therapy—specifically, the reinfusion of stem cells into aged tissues—can delay or even reverse aging.

Another theory posits that aging is caused by inflammatory responses within various tissues. During the process of neurodegeneration, the brain exhibits significant inflammatory activity. Therefore, whether anti-inflammatory interventions can slow down these age-related neurodegenerative diseases has become a highly active area of research.

In addition, other strategies actively explored in the field of anti-aging include restoring telomerase activity, employing epigenetic modulators, and reshaping proteostasis networks.

Aging is a systematic and complex process. Are there any simple methods currently available to slow it down? Academician Wang Xiaodong shared insights on the latest research findings.

Currently, two renowned "miracle drugs," metformin and rapamycin, are undergoing clinical trials for anti-aging purposes. Some studies have demonstrated that long-term administration of these two drugs to Caenorhabditis elegans and even mammalian models such as mice can indeed extend lifespan.

At the event, Academician Wang Xiaodong also presented a research finding: SIRX596, a proprietary small-molecule compound developed by Sironax (Vitaerlon), demonstrated anti-aging effects in mouse feeding studies. Sironax was co-founded in 2018 by Academician Wang Xiaodong and Dr. Zhang Zhiyuan, his colleague at the National Institute of Biological Sciences, Beijing, with the aim of treating age-related degenerative diseases and thereby slowing down the aging process.

In this experiment, researchers divided mice into three groups. One group consisted of young mice aged three months, equivalent to 25-year-old humans; the second group comprised aged mice fed a standard mouse diet for two years, equivalent to 80-year-old humans; and the third group consisted of aged mice fed a mouse diet supplemented with the compound SIRX596 for two years.

Externally, the second group of mice exhibited typical signs of aging, including obesity, scoliosis, sparse fur, and graying. The third group of mice did not display age-related morphological changes, and their appearance showed no significant differences from that of the first group of young mice.

In terms of athletic performance, the experimental GIFs presented by Academician Wang Xiaodong show that during a running wheel competition among three groups of mice, the second group of aged mice was the first to drop out, falling off the wheel in under two minutes. The third group of aged mice ran for a slightly shorter duration than the first group of young mice, but the difference was minimal and statistically insignificant.

This demonstrates that by understanding the aging process, designing compounds, and then intervening in this process—even through crude intervention at a specific node—it is possible to achieve the goal of delaying aging.

Although the results from mouse trials are promising, Academician Wang Xiaodong also acknowledges that proving whether this drug can truly delay human aging requires evidence from two aspects:

1. Is the anti-aging effect of drugs mediated through specific targets and drug actions?

2. Are the Anti-Aging Mechanisms Observed in Mice Effective in Humans?

Finally, Academician Wang Xiaodong stated that there are numerous strategies for combating aging, necessitating exploration from multiple perspectives to truly identify critical, and even initiating, nodes within the aging process. Research should focus on aging-related processes, including cognitive decline, metabolic decline, reproductive aging, immune senescence, and musculoskeletal degeneration, to explore the biological molecular mechanisms and intervention strategies and methods associated with aging. The goal is to further extend the period from youth to middle age, prevent and treat aging-related diseases, and ultimately achieve healthy aging.