Can we slow down or, better yet, reverse ageing?

Ageing is defined as the decline in physiological function with decreased survival and fertility rate as age increases. As the elderly population grows in the next 20 years,  ageing is likely to become a major risk factor for disease-induced mortality, and it is of clinical relevance and interest to search for remedies. 

Methods for slowing down ageing

Epigenetic reprogramming: Epigenetics is defined as the regulation of gene expression by means other than an individual’s DNA sequence. Epigenetic changes occur at various levels when the organism ages. Epigenetic reprogramming is the reset of epigenomes of somatic cells to establish pluripotency. iPS cells were a revolutionary technique to revert differentiated cells to the pluripotent stem cell stage by over-expression of Yamanaka factors to erase epigenetic marks and restore youthfulness to cells. Short-term cyclic expression of Yamanaka factors has been shown to reduce age-associated hallmarks without the formation of tumours in premature ageing mouse models.  

Lengthening of telomeres: Telomeres are short repetitive DNA sequences at the end of each chromosome and they help to protect chromosomal DNA ends and prevent degradation. Telomere shortening happens as an organism ages; some have referred to telomeres as the “biomarker of ageing”. Extensive studies are working on reversing ageing through the reactivation of telomerase, an enzyme that extends the length of telomeres. 

Senolytic drugs: Senolytic drugs induce apoptosis of senescent cells selectively. Senescent cells, which are known to accumulate in different types of tissues as age increases, enter an irreversible cell-cycle arrest, undergo several phenotypic changes and are resistant to apoptosis. These cells release chemokines, pro-inflammatory cytokines and pro-thrombotic factors that may damage tissues, alter tissue structure and increase fibrosis. The new class of drugs, senolytics, are inhibitors of the identified senescent cell anti‐apoptotic pathways and were demonstrated in previous studies to extend lifespan and improve the function of stem cells in ageing mouse models. 

Dietary supplements of antioxidants:  Oxidative damage increases and antioxidant function decreases with ageing. Antioxidants, which are substances that inhibit or reduce the oxidation of substrate, may therefore be able to slow down ageing and increase the lifespan of an organism. Studies have demonstrated that dietary supplements of antioxidants, such as vitamins C and E, can increase the lifespan of model organisms. 

Caloric restriction:  Caloric restriction, which is the reduction of food intake by 30-50% without malnutrition, is reported as the most effective method to extend lifespan as well as health span in a number of species.

Conclusion and Perspectives 

There have been massive efforts in researching methods to slow down ageing for several decades. With technological advancement, we began to understand more about the mechanisms of ageing and develop strategies based on these mechanisms to slow down ageing. However, ageing is a complex process whose full mechanism is yet to be discovered. It is foreseeable that there will be more interdisciplinary collaboration in the next 50 years to dissect the mechanisms of ageing. With the rise of big data analytics, it is predicted that the new era of informatics will help to advance biomedical research in the coming years.

Image description: portrait of man holding a younger black and white photo of himself in front of his face

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