Longevity: living long & prospering?

Longevity is a buzzword that currently attracts considerable attention, from individuals who’d like to hack their metabolism in support of retaining a youthful appearance or rewinding their biological clock to a younger age, to governments who seek to retain their constituent members of society healthy and productive as long as possible, to investors who have identified aging as a condition that can be – while not halted – delayed through the repurposing of existing (e.g., rapamycin, as discussed in https://link.springer.com/article/10.1007/s11357-020-00274-1) or development of new treatments (such as discussed in https://www.wired.co.uk/article/aging-disease-biology).

Societies, notably in the developed world, currently experience a demographic paradigm shift in the form of an evolving population structure that is at the same time shrinking and tilting towards the old. This is dramatically expressed in what is called the old-age dependency ratio (OADR), i.e., the proportion of people aged 65 years or older relative to those of working age. For example, the UK OADR rose from around 10% in 1922 to nearly 30% currently and is projected to reach 50% by 2111 (for a detailed discussion, read https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(21)00250-6/fulltext).

Corresponding concerns are that these developments will at the same time decrease economic growth (because the productive fraction of the population decreases) and increase expenditure due to rising healthcare costs. Prospective antidotes are a potential increase in the official retirement age; new longevity working models; and, a marked shift towards preventative care rather than treatment of conditions once they are manifest.??

Of course, there is more to the longevity field than just the buzz. It’s based on decades of research and, more recently, fuelled by significant bouts of investment. A recent special edition of National Geographic (https://www.nationalgeographic.co.uk/science-and-technology/2022/12/can-ageing-be-cured-scientists-are-giving-it-a-try) provides a good overview of the topic and the research that is going on in the longevity arena.

A couple of companies (https://altoslabs.com/,?https://www.calicolabs.com/, https://hevolution.com/) have been created recently to tackle aging; not to prevent death but to increase lifespan and, most importantly, health span (the fraction of the time we are alive AND fully functioning).

These new ventures (Hevolution is an NPO created by the Saudi government) aim to tackle the complex biology of aging through large-scale investment (Altos raised USD 3bn, to begin with), unrestrained models of work (it's ok to fail repeatedly), more effective collaboration, and (which may be doubted by critics) democratization of outcomes (a recent discussion is available here).

In comparison to these efforts, government funding is trailing behind, potential reasons being (i) the long-term and risky nature of these endeavors and (ii) conflicting (short-term) funding priorities.

Overall, funding longevity projects remains a challenge, whether it's from the government or private players. Most projects are small-scale and/or in the fund-seeking phase but many of them seek to unravel the mechanisms of aging at the molecular level, to design and develop effective treatments (pharmacological and otherwise).

What is in focus already at present is that 'behaving well' (lifestyle) can effectively modify many disease risks, and aging, as has been shown already in numerous studies (e.g. Association of step counts over time with the risk of chronic disease in the All of Us Research Program | Nature Medicine). In short, there are easier ways to achieve longevity and greater health span (this article neatly summarises a few of them https://theconversation.com/life-extension-the-five-most-promising-methods-so-far-169881); but, since change is hard, and humans are creatures of habit, popping a pill may be the preferred option for many...

One of the challenges faced by scientists is that aging is difficult to define, although an effort has been made in 2013 to overcome this:?The Hallmarks of Aging: Cell.

Another one is that prospective medico-scientific solutions (an 'anti-aging pill') may increase inequality in already fractured societies, creating an 'aging well' elite and the sickly rest. This ought to be considered carefully against the prospect of increased healthcare spending as we grow older, notably in societies that do not offer free public health care are the point of need.

A recent report, by Deloitte, (https://www2.deloitte.com/us/en/pages/life-sciences-and-health-care/articles/longevity-science.html) highlights the essential outcome of any longevity-centric research or intervention: extending life span and/or health span. While the latter is at the heart of most scientific and commercial endeavors today, it’s likely that innovative treatments will positively affect the former as well.

Technically, life and health span can be evaluated using two recognized mortality metrics: Premature Years of Life Lost (PYLL or 'life span') and Years of Life with Disability (YLD or 'health span'). Significant improvements have been made in recent years in improving life span, specifically through the development of new therapeutic treatments for cancer and cardiology.

In contrast, improvements in health span have been less widespread. In fact, certain disease areas, notably the whole complex of ENM (Endocrine, nutritional, and metabolic) disorders, have seen a marked decline over the last years. This is largely driven by worsening lifestyle behavior (e.g., increasing body mass index [BMI] and type 2 diabetes) and the growing elderly population (aging is the leading risk factor for neurological and musculoskeletal disorders).

In support of a necessary shift from sick care to health care, the Deloitte paper recommends a shift from individual disease and symptom management to disease-agnostic preventative care as a critical component of the longevity approach. Instead of single-disease treatments, it recommends a focus on addressing a variety of diseases that stem from common hallmarks of aging, adopts a biological systems view, and addresses / modifies lifestyle behaviours.

Such a shift is only possible if data gathering analysis is of high resolution, multi-dimensional, and continuous, facilitated by the deployment of sensor ecosystems that are securely and reliably taking measurements and providing actionable, intelligible feedback which allows the individual (and/or a professional facilitator) to manage his/her health and well-being effectively.

An increasing number of studies demonstrate that such a scenario is not only possible (e.g. https://www.nature.com/articles/s41591-022-01981-2) but technically feasible (e.g. https://www.nature.com/articles/s41586-020-2669-y or https://www.nature.com/articles/s41591-022-01980-3).