Top Anti-Ageing Targets
Top Targets for Anti-Aging Interventions
One of the undeniable results of the publication of the Hallmarks of Ageing was providing a focus for research and therapy on the mechanisms of ageing. The science of anti-aging is evolving quickly, with research highlighting key biological targets that slow or even reverse aspects of the aging process. Here, we look at the top seven targets for anti-aging interventions as it currently stands.
1. Cellular Senescence
Senescent cells are cells which no longer divide and cease performing their usual function. They accumulate with age, releasing inflammatory signals that contribute to tissue and systemic deterioration, known as the SASP Senescence associated secretory phenomenon. Targeting senescent cells, known as senolytic therapy, is an exciting area of research.
Example: The drugs dasatinib and quercetin have shown promising results in selectively clearing senescent cells in mice, reducing age-related physical dysfunction.
Kirkland JL, Tchkonia T. Cellular Senescence: A Translational Perspective. EBioMedicine. 2017.
2. Telomere Maintenance
Telomeres, protective caps at the ends of chromosomes, shorten with each cell division, eventually triggering cellular aging. Telomerase activation aims to maintain or lengthen telomeres, preserving cellular health.
Example: TA-65, a compound derived from the herb Astragalus membranaceus, has shown potential to lengthen telomeres in humans, improving immune function.
Harley CB, Liu W, Blasco M, et al. A natural product telomerase activator as part of a health maintenance program. Rejuvenation Research. 2011.
3. Mitochondrial Function
Mitochondria are essential for cellular energy production, and also perform a series of essential metabolic and signalling functions within the cell. Their decline is closely associated with aging. Supporting mitochondrial health can help counteract this process.
Example: Urolithin A, a compound derived from pomegranates, promotes mitophagy (the removal of damaged mitochondria) and improves muscle health in older adults.
Andreux PA, Blanco-Bose W, Ryu D, et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolism. 2019.
4. Epigenetic Reprogramming
Epigentics describes the state of genetic expression – which genes are ON and which genes are OFF. There is a different epigenetic pattern for every cell type. Epigenetic patterns of young and aged cells have been identified and mapped. Epigenetic reprogramming can reset these markers to a more youthful state – making old cells young again.
Example: The Yamanaka factors (Oct4, Sox2, Klf4, c-Myc) have been used to partially reprogram cells, rejuvenating tissues and even reversing signs of aging in animal models.
Ocampo A, Reddy P, Martinez-Redondo P, et al. In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell. 2016.
5. Stem Cell Therapy
Stem cells play a key role in tissue regeneration, but their numbers and function decline with age. Stem cell therapy aims to replenish and rejuvenate these cells, allowing them to divide and replenish tissues as would occur naturally in youthful organs and tissues.
Example: Mesenchymal stem cells (MSCs) have been used to repair and regenerate tissue in several conditions, including osteoarthritis and age-related degeneration.
Galipeau J, Sensebe L. Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities. Cell Stem Cell. 2018.
6. Autophagy Induction
Autophagy is a natural process by which cells remove damaged components and recycle them. This process becomes less efficient with age, allowing accumulation of damaging by products within and without of cells. Enhancing autophagy helps clear cellular waste, potentially slowing aging.
Example: Spermidine, a compound found in fermented foods, has been shown to induce autophagy, improve cell health, and even extend lifespan in animal models.
Eisenberg T, Knauer H, Schauer A, et al. Induction of autophagy by spermidine promotes longevity. Nature Cell Biology. 2009.
7. Nutrient Sensing Pathways
Nutrient-sensing pathways like mTOR and AMPK regulate how the body responds to food intake. Modulating these pathways mimics the beneficial effects of caloric restriction, which is associated with increased lifespan.
Example: Metformin, a common diabetes medication, activates AMPK and has shown promise in extending lifespan and reducing age-related diseases.
Pozzi, M., Susini, P., Di Seclì, D. et al. The anti-aging role of metformin, clinical applications to pursue the longevity road. Eur J Plast Surg 47, 65 (2024). https://doi.org/10.1007/s00238-024-02211-3
Conclusion
Each of these targets is a promising avenue for anti-aging interventions, providing both preventive and therapeutic potential to slow down or even reverse aspects of aging. Many interventions positively affect multiple pathways. Many interventions are currently available, providing practitioners and individuals cost effective safe and effective ways to intervene today against the ageing processes. As research progresses, we can anticipate that more of these approaches may move from the lab to real-world applications, helping individuals lead healthier, longer lives and one day defeating ageing.
Copyright Dr Christopher Maclay 2024. All rights reserved.
Disclaimer: This information is for educational purposes only, it does not constitute medical advice. Please consult with your health care practitioner for personalised medical advice.