DefinePK

Abstract

Ageing, conventionally measured as an inevitable biological process, is one of the major areas of leading-edge scientific research. Nowadays, the field of senolytics, telomere extension and other cellular rejuvenation techniques intended at tackling ageing at its foundation have been studied by scientists as potential new options for extending human life and refining health in later years.1
Senolytics, Aging Reversal and Signaling the End of Senescence
The class of drugs known as senolytics, which kill senescent cells, have seen great promise in preclinical and very early human trials. Senescent cells, also termed zombie cells, accumulate with a normal ageing process and contribute to inflammation, tissue malfunction, and age-related disease. Senolytics, the drugs that selectively remove these cells, improve health, reduce frailty and it might even extend life.2 Such drugs as dasatinib and quercetin have been effective in animal models and ongoing human trials in checking their lifelong impact on ageing-related disorders like osteoarthritis and cardiovascular failure. A strategy of senolytics has proven to be promising against age-related decline due to its ability to target specific pathways that allow senescent cells to persist and evade regular cell death. Senolytics can accomplish this by acting in BCL-2, PI3K/AKT, and p53/p21 pathways, restoring tissue homeostasis and decreasing chronic inflammation.3 Dasatinib, a renowned tyrosine kinase inhibitor initially developed for leukaemia, and Quercetin, an exceptional natural flavonoid with brilliant senolytic properties, are two of the most prominent senolytics. Often, these both work well synergistically to enhance each other’s effects. An alternative flavonoid, fisetin, also has great potential for extending lifespan in experimental mice. Additionally, Navitoclax was identified for its ability to induce apoptosis of senescent cells through a selection of BCL-2 family members.4
Telomere Extension: The Key to Cellular Immortality
Telomeres are sequences of DNA located at the end of chromosomes that degrade with each cell division, leading to cell dysfunction.  Telomerase, an enzyme that replaces telomeres, has been shown to extend the cellular lifespan and possibly reverse the ageing process in various studies.5 Current studies include gene therapy to increase telomerase activity, which has been successful in animal models. The main challenges are the potential for uncontrolled cell growth and cancer. Telomere extension offers a great prospect to enhance the quality of human life and increase the lifespan primarily through two ways. First, there is telomerase activation, a process that reverses the shortening of telomeres. Telomerase is a ribonucleoprotein that adds tandem repeats to the ends of telomeres.6 It is mostly inactive in somatic cells, but this is very important in stem cells, germline cells and cancer cells. Gene therapy or the use of tiny molecules such as TA-65 could perhaps be used to deliver telomerase to ageing cells and resuscitate it, or reactivate it and increase its activity. Other research has shown that specific nutrients and hormones can increase telomerase activity, so there may be other avenues to be explored to regrow cellular health as well.7
On the other hand, an interesting mechanism called Alternative Lengthening of Telomeres (ALT) is working independently from telomerase mainly in cancer cells. ALT allows cells to extend their telomeres by copying telomeric DNA from one chromosome to another by using DNA repair mechanisms, such as homologous recombination. Blocking ALT could be an important cancer research target since ALT inhibiting could do much to stop the infinite proliferation of cancer cells.8
 
Beyond Senolytics and Telomeres: Additional Promising Interventions
Other therapies are gaining popularity in longevity therapy, besides senolytics and telomere extension. Metabolic pathways have been shown to regulate lifespan when metformin and rapamycin are mimicking calorie restriction. In addition, there are great breakthroughs from regenerative medicine in the renewing of ageing organs and tissues, including stem cell therapy and tissue engineering.9
The Ethical and Social Consequences of Prolonged Lifespan
While these scientific advances are interesting, they involve equally or even more serious ethical and societal dismays. What will be the implications of being able to confidently dramatically postpone or even, in some cases, reverse ageing on the global dynamics of population, economic systems and health systems? To prevent a future in which only the wealthy can afford extended lifespans, anti-ageing medications must be available as well.10, 11
The Future of Longevity Medicine
Anti-ageing research has moved beyond the realm of science fiction. With continuous advances in biotechnology, the idea of reducing, halting, or even reversing parts of ageing is becoming more real. However, converting these discoveries into safe and effective medicines for general usage is still a considerable issue. As research advances, the focus must stay on guaranteeing not only a longer but a healthier life.12
The promise of healthy longevity is closer than ever, but it will necessitate careful consideration of scientific, ethical, and cultural issues. The next few decades could redefine what it means to be old, turning ageing from an unavoidable decline into a controlled, treatable condition.