As modern societies are becoming older, the projected percentage of the total population over 65 years old is expected to reach 16.2% in 2050. While we entered the last decade with a proportion not higher than 8%, this calls for new challenges and questions about our future. This worldwide trend is greatly explained by the successful developments of modern medicine. From the eradication of numerous infectious diseases, to the most recent developments in gene therapies and the increasing access to treatment all around the world, we are witnessing a significant growing of the population’s lifespan.
Living longer inevitably opens the question: to what cost? Indeed, aging is the major risk factor for most human pathologies including cancer or Alzheimer’s. Risk of death from these diseases is 100 to 1000 times higher after the age of 65 years than in the first decades of life of an individual. Extending lifespan without assuring healthier old age does seem odd. This is why understanding the mechanisms responsible for aging is of central interest. These processes are characterized by a progressive decline in cellular, tissue, and organismal integrity that can be explained by the so-called hallmarks of aging. It includes chronic inflammation, cell dysfunction, stem cells that lose their ability to regenerate tissues, and the increase of senescent cells that accumulate in tissues and accompanies diseases.
Importantly, several strategies already exist that partially counteract the process of aging including exercise, caloric restriction or intermittent fasting. In addition to the growing number of studies demonstrating conservation of the aging process across model organisms, growing body of evidences show that similar interventions, such as the previously mentioned dietary restrictions, increase lifespan in almost every species examined. For this specific intervention for instance, beneficial physiological changes accompanied the lifespan extension such as increased stress resistance and interestingly reduce incidence of age-related diseases.
On the other hand, not only can changes in lifestyle affect longevity, but some pharmacological treatments have also been studied for their capacity to ameliorate age-associated hallmarks. Exciting progresses in the field of aging have led to the first drug to be tested for its age-targeting effects: Metformin. Indeed, the mechanisms whereby this previously anti-diabetic drug attenuated hallmarks of aging have been demonstrated. This makes Metformin an attractive gerotherapeutic drug to translate to human trials. More recently, another drug that sparked the interest of researchers for the last decade is in the centre of a trial with a different mammal, but certainly not the least: the dog. The Dog Aging Project will test the effects of the drug Rapamycin in hundreds of dogs in a double-blinded, placebo-controlled trial, and assess its effect on immunity, cancer, cognitive and heart function.
Finally, while some of these interventions seem to affect an organism’s healthspan and lifespan more than other, the growing field of aging is also developing strategies for targeting the causes of age-related diseases at the level where it occurs: the cell. This strategy is specifically targeting the removal, repairing and replacement of cellular and molecular damages that have accumulated in tissues with time. It will allow the retrieval of the body’s cells and biomolecules normal interactions, and its tissues normal and healthy functioning. Targets include the clearance of extracellular and intracellular aggregates, elimination of senescent cells, epigenetics, and tissue engineering.
With the ever-growing number of aging companies, all these lifestyle strategies, pharmacological trials, or new molecular approaches for the reversal of cellular aging will push the field forward. Eventually, it will allow the development of future therapeutic strategies aiming at the improvement of human healthspan and lifespan.
Writing by: Lucas Schoenfeldt.