Aging: therapeutics for a healthy future

https://doi.org/10.1016/j.neubiorev.2019.11.021Get rights and content

Highlights

  • Approaching aging as a target is a new therapeutic frontier.

  • Potential of modifying aging processes can be transformative for medicine.

  • Multiple mechanisms have the potential to deliver improvements in healthspan.

  • Challenges of science, translation, economics and regulation need to be navigated.

  • Encouragement from collaboration between academia, industry, funders and regulators.

Abstract

Increased healthcare and pharmaceutical understanding has led to the eradication of many childhood, infectious and preventable diseases; however, we are now experiencing the impact of aging disorders as the lifespan increases. These disorders have already become a major burden on society and threaten to become a defining challenge of our generation. Indications such as Alzheimer’s disease gain headlines and have focused the thinking of many towards dementia and cognitive decline in aging. Indications related to neurological function and related behaviors are thus an extremely important starting point in the consideration of therapeutics.However, the reality is that pathological aging covers a spectrum of significant neurological and peripheral indications. Development of therapeutics to treat aging and age-related disorders is therefore a huge need, but represents a largely unexplored path.

Fundamental scientific questions need to be considered as we embark towards a goal of improving health in old age, including how we 1) define aging as a therapeutic target, 2) model aging preclinically and 3) effectively translate from preclinical models to man. Furthermore, the challenges associated with identifying novel therapeutics in a financial, regulatory and clinical sense need to be contemplated carefully to ensure we address the unmet need in our increasingly elderly population. The complexity of the challenge requires different perspectives, cross-functional partnerships and diverse concepts. We seek to raise issues to guide the field, considering the current state of thinking to aid in identifying roadblocks and important challenges early. The need for therapeutics that address aging and age-related disorders is acute, but the promise of effective treatments provides huge opportunities that, as a community, we all seek to enable effectively as soon as possible.

Section snippets

Aging – what are we attempting to treat?

Many consider aging as a purely chronological phenomenon; it is an immutable fact that we all get older. However, this is a simplification as individuals all age functionally in different ways and the concept of “biological aging” is more relevant than chronological aging (Khan et al., 2017). When we consider biological aging, we have a therapeutic target, not simply targeting getting old, rather treating physiological decline that is manifested by dysfunction and morbidity in late life. When

Issues involved in developing anti-aging therapies

A therapeutic that halts or prevents aging, putting off the onset of a debilitating disorder, could lead to a longer life. Extending life on the face of it is highly positive; the vast majority of the population looks forward to a long and fruitful life. However, if anti-aging therapies only increase lifespan without increasing healthspan it will just increase the population of diseased elderly, increasing healthcare spending and providing an undesirable, unsustainable, future for society. If

What may anti-aging therapeutics look like?

Is a golden bullet of a single drug to impact aging biology a realistic scenario? The diversity of age-related disorders, the multitude of potential endpoints, the complexities of genetic risk factors and environmental challenges accumulating over a lifetime all make a single therapeutic unlikely. However, if there are fundamental underlying mechanisms, such as cellular senescence or failure of proteostatic maintenance, or a natural mixture, such as plasma or a fraction of plasma able to

Funding and regulatory issues

Associated with the treatment of aging is a new set of interpretations of clinical success that go beyond purely scientific concepts. In particular, advancing a therapeutic for aging means that we have long timelines, yet to be validated outcome measures and a lack of clarity about the regulatory environment for such therapies. These challenges impact how aging therapeutics will be funded and considered. Nonetheless, there is an appetite by the broad community to achieve these goals and thus

Conclusions

We are at an exciting juncture where the realities of anti-aging therapies are upon us, and discussing how we can practically advance such approaches is a necessity. Even though a majority of research and therapeutic development focuses on individual domains such as neuroscience or behavior alone, thinking in the context of a systemic impact as we age provides wholly new opportunities, not only to tackle neurological disorders, but a spectrum of age-related ailments. The involvement of multiple

Acknowledgements

The authors thank Gabrielle LeBlanc (Leblanc Bioscience Consulting, Berkeley, CA) for help in writing the manuscript. This review is based in part on an open scientific satellite symposium titled “Aging: Therapeutics for a Healthy Future” held in conjunction with the 46th Annual Society for Neuroscience meeting in 2016, sponsored and organized by Charles River Laboratories. The meeting panelists included: Robert Hodgson (CNS Biology, Takeda, San Diego CA), Brian K. Kennedy (Yong Loo Lin School

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