Healthy Longevity: Aging Hallmarks and Innovative Strategies

Aging is marked by a gradual decline of physiological fitness and the accumulation of cellular damage, resulting in reduced function and increased disease risk. Over the past 20 years, research and development in aging and healthy longevity have expanded and diversified. Recently, experts from CAS, Cedars-Sinai Medical Center, Procter & Gamble, and Harvard Medical School joined for a webinar on November 14 to provide an overview of the current aging research trends and their insights into specific healthy aging strategies. Access the webinar recording here to discover how aging research and innovations are transforming human health and longevity.

Key highlights from the webinar

Janet Sasso started the webinar, setting the stage with a high-level overview of the aging research field (See Figure 1). She discussed research efforts alongside publication trends of aging hallmarks and recent healthy aging strategies, all derived from the CAS Content Collection™. She continued the discussion by diving into biological processes such as genomic instability and telomere attrition, reactive oxygen species and oxidative stress, along with glycation and advanced glycation end products and their relationship to aging. She also discussed publication trends on age-associated diseases and strategies to combat aging before finishing by showing the therapeutic clinical trial landscape surrounding this research.

Dr. Tamara Tchkonia started her talk by introducing the interconnected mechanisms of aging and how they contribute to the pathogenesis of chronic disease before showcasing the main star of her talk, cellular senescence. Dr. Tchkonia explained the biological process of cellular senescence and different conditions that have a high burden of senescent cells. She shared research that shows a causal link between senescent cells and functional decline, strategies to target senescent cells, and lastly, clinical trials related to senescent cells that are in the development pipeline.

Dr. Gosia Klukowska continued the presentation by sharing her knowledge on aging and the oral cavity. She started with Procter & Gamble’s extensive research history in aging, then discussed functional and physiological changes of the aging oral cavity alongside key findings from oral aging research studies. Dr. Klukowska discussed the oral conditions of the aging population  and their connection to systemic diseases. She finished her presentation by highlighting oral care products that can benefit the aging population.

Dr. David Sinclair concluded the presentation with an overview of his lab’s research from the past 25 years. Starting with epigenetics and the information therapy of aging, Dr. Sinclair shares how they know cells contain a repository of youthful information that allows them to be rejuvenated into a younger state. He then talked about the strategies to control epigenetic factors to treat age-related diseases. He also shared positive study results of neuronal cell age reversal and age-related blindness in mice. They hope to use the same gene therapy treatment in humans starting in August 2025 with the first epigenetic age reversal clinical trial in humans. Finishing his presentation, he also shared hopes of making treatment cheaper. Dr. Sinclair also showed recent research where they used DASH-AI to screen and find chemicals that can do the same thing as gene therapy to rejuvenate mouse and human cells. He discussed positive study results of preclinical studies showing gene rejuvenation by these chemical compounds alongside positive clinical trial results.

To wrap up, attendees asked many questions, from the function of senescent cells and age-related diseases to questions about the aging research clinical trial landscape. Attendees also inquired about the oral microbiome, newer anti-obesity drugs, and their relationships to aging.

Key questions from the webinar

How can senolytic drugs bind to senescent cells and what is the risk of introducing cancer?

Senolytic drugs are targeting one or more pathways related to senescent cells, disabling these pathways. Regarding cancer, clearing and reducing senescent cells reduces the risk of cancer.

Which aspects of the clinical trial research landscape are most exciting to share?

The most exciting aspect of the clinical trial landscape that we saw when evaluating the CAS Content Collection, was how broad and expansive the therapeutic options are when looking at solutions for healthy longevity. Therapeutics include both pharmaceutical interventions such as mTOR inhibition and senolytic agents along with non-pharmaceutical interventions such as caloric restriction, physical exercise, and gut microbiome modulation.

How close are we to using Yamanaka factors to regenerate human neurons, and what challenges remain? If successful, could this approach repair neuronal and axonal damage in advanced Alzheimer's disease?

Human neuron cells are being rejuvenated in the lab every week, but that is not the human brain, just cells in a dish. Using gene therapy for Alzheimer's is going to be challenging, and more likely a single compound or chemical cocktail will be used more widely. We can expect to see great progress in this field within the next five years.  

Does the microbiome (gut or oral) have any effect on oral aging and health?

When someone’s microbiome is imbalanced, it can affect inflammation in the oral cavity and it can accelerate the aging of oral tissue with oxidative stress.

How is caloric restriction and body weight control related to aging? Can autophagy clear senescent cells during caloric restriction?

A healthy lifestyle and weight control can reduce triggers of senescent cells but in existing conditions with high senescent cells, caloric restriction has a synomorphic effect which can modulate the senescent cell secretory phenotype and have a benefit, but whether it eliminates or prevents senescent cells is still not determined and it is still being investigated.

How will the newer weight control drugs play into healthy longevity?

Weight control and senolytic drugs prevent senescent cell accumulation and help research animals stay healthier and more insulin sensitive, even in the context of obesity, but if they eliminate senescent cells is still under investigation. The newer weight control drugs have shown great promise for many different areas besides weight control, such as cardiovascular health and brain health. They may work by deleting senescent cells or reducing inflammation, but again, this is all still being investigated. There is still much research to be done on these drugs to understand therapeutic and adverse effects along with their mechanism of actions but offer hope and promise to many individuals for both aging and disease prevention.

Learn more 

Download our executive summary on anti-aging research to learn more about the key trends shaping healthy longevity research. See the recording and the associated slides from the webinar here.