Introduction

The Biology of Ageing must now become integrated into the approaches of our specialty. We had to wait for the baby-boom to become the papy-boom, and now the super papy-boom, for many clinical and/or fundamental specialties in biology and health to take an interest in ageing—for health reasons, but also for the wider societal and economic issues.

Many organ specialties are increasingly interested in biological and molecular ageing. Geriatric medicine and its professionals must now better understand biological and molecular ageing, not only of specific organs, but above all of the dysfunctions related to geriatric syndromes.

Despite its name, our discipline is young. After having clearly defined geriatric syndromes and polypathology, frailty and even more recently preventive interventions for healthy ageing, the biology of ageing must be explained and taught to future clinicians. We must motivate students and young geriatricians to invest in research. Understanding and learning the biology of ageing without a purpose can be off-putting for clinicians. However, it takes on greater meaning when approached from the point of view of geriatric syndromes [1, 2].

Nine key hallmarks of ageing have been identified: cellular senescence, epigenetic alterations, telomere attrition, mitochondrial dysfunction, genomic instability, altered intercellular communication, deregulated nutrient-sensing, stem cell exhaustion, and loss of proteostasis [3, 4]

Geriatric syndromes may seem to be somewhat removed from such biological and molecular hallmarks, but experimental models can serve as “intermediary steps” from human to biology (Fig. 1). For examples, cells and yeast present rapid proliferation and short lifespan. Caenorhabditis elegans and Drosophila can serve as screening models for pro or anti-ageing drugs. Mice offer numerous possibilities to mimic diseases (transgenic mice). Naturally selected Senescence Accelerated Mice (SAM) can be used during a short period of time (half lifespan compared with non-SAM mice) to study biology in premature systems depending on the SAM model. Microcebe lemurs present a spontaneous high incidence of Alzheimer’s disease-like behavior, physiological and molecular ageing. Finally, monkeys have proven to be a good model to confirm experimentally the positive effect of caloric restriction on lifespan [5, 6].

Fig. 1
figure 1

From geriatric syndromes to key hallmarks of ageing

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The future for the biology of ageing is no longer merely to improve our understanding of the fundamental pathways of ageing, but now also includes better control of ageing. We need to focus our immediate efforts principally on slowing accelerated ageing in non-communicable diseases: the future will certainly lead us towards questions surrounding the prevention of physiological ageing, with all the ethical reservations that will be required.

They are many ways to combat ageing, the best of which is of course multidimensional prevention, but it could also be targeting specific organs, or else considering many factors in a global assessment. For example, stem cell transplantation can be used for targeted organs or tissues, while cloning to reset the telomere clock or pharmacological interventions represent a more global approach.

Some therapies against premature aging have been identified, such as targeting anti-apoptotic pathways, PI3 Kinase, the p53 and p16 axes, and NF-κB regulation. The development and widespread clinical use of senolytics have come about following identification of the Senescence-Associated Secretory Phenotype (SASP). The accumulation of senescent cells is likely to contribute to inflammageing, since the SASP is produced by senescent cells and includes production and secretion of pro-inflammatory cytokines, chemokines, soluble receptors, metalloproteases, certain protease inhibitors, and growth factors [7,8,9].

Today, senotherapy (removal of senescent cells) regroups 5 classes of drugs collectively named “senolytics”: senoblockers, senomorphics, senostatics, senomodulators, senosuppressors (Fig. 2) [10, 11].

Fig. 2
figure 2

Senotherapy: 5 class of “senolytics” and their target action. Senescence Associated Secretory Phenotype (SASP). 1: Senomorphics, small molecules inhibiting SASP. 2: Senomodulators, drugs suppressing SASP activity. 3: Senostatics: drugs interfering cells entering to senescence. 4: Senoblockers, agents affecting epigenetic regulators to reactivate programs of youthfulness and regeneration. 5: Senosuppressors: therapeutics slowing down senescent cell accumulation rate

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Conclusion

The Biology of Ageing not only represents an asset for geriatric medicine, but also a challenge for the future. Biology of Ageing articles submitted to EGM should ideally be linked to geriatric questions and syndromes. From chemistry, molecular and cellular biology to drug development via preclinical animal studies, articles must give fundamental results useful for the future of Geriatric Medicine. The final aim is to improve the care of older people.

While geriatic medicine does not hold the monopoly of interest in the biology of ageing, our specialty nevertheless encompasses much of the clinically relevant expertise, as well as being primarily concerned with the ultimate purpose of this field of research.