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Healthspan therapies and interventions
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Healthspan therapies and interventions

2.3.3

Sub-Field

Healthspan therapies and interventions

Healthspan extension can already be achieved through several approaches, including specific diets, calorie restriction and exercise, 16L. Fontana‘Caloric Restriction and Cellular Senescence’
Mechanisms of Ageing and Development, Vol. 176, p.19.
 17R. G.‘A Molecular Signature Defining Exercise Adaptation with Ageing and in Vivo Partial Reprogramming in Skeletal Muscle’
The Journal of Physiology, Vol. 601, p.763.
 but drugs are being developed to mimic the effects of these interventions.

Future Horizons:

×××

5-yearhorizon

Anti-ageing drugs and regimens begin clinical trials

Tests begin to validate anti-ageing drugs and regimens. In the wake of successful trials measuring indirect effects on the diseases of ageing, first clinical trials are approved to delay age onset directly. AI, baked into a proliferation of wearable devices, apps and trackers, allows people to personalise exercise and diet interventions to maximise their healthspan. Results emerge from first trials of cell and gene therapy to slow ageing in dogs. Rapamycin and metformin trials, along with canine and non-human primate work, yield results that begin to reveal the cellular mechanisms they act on and elucidate the viability of mTOR inhibition as a single therapy that can knock down the dominoes of age-related conditions. Multiple approaches to senescent cells yield information about which work best under which circumstances.

10-yearhorizon

Clinical trials clarify promising drugs

Health plans begin to prescribe validated age-delaying therapies. Research from comparative biology of long-lived species, including naked mole rats, is tested in humans via gene therapy or pharmacological intervention. The first gut microbiome interventions are tested in humans to slow onset of age. Trials begin to combine two or more drugs like metformin and rapamycin. All findings feed back into fundamental geroscience, adding new insights.

25-yearhorizon

Early preventative interventions see success

The traditional medical model of “one disease, one treatment” is disrupted by drugs that have multi-modal effects. Rather than picking up age-related problems like cancer and dementia in their late stages, preventative interventions stop people getting ill in the first place. Prescriptions for drugs that have been validated in trials are dispensed for some people at particular risk of abnormal ageing early in life, say in their 20s, preventing the ageing process rather than trying to reverse it later.

These include drugs that target sirtuins and drugs that inhibit the mechanistic target of rapamycin (mTOR) networks, whose signalling is increasingly understood to influence longevity and ageing. mTOR inhibition has been shown to increase lifespan in animal models and elderly humans.18J. B.‘MTOR Inhibition Improves Immune Function in the Elderly’

Science Translational Medicine, Vol. 6.
19Q. Xue‘Rapamycin Increases Grip Strength and Attenuates Age-Related Decline in Maximal Running Distance in Old Low Capacity Runner Rats’
Aging, Vol. 8, p.769.
 20T. Weichhart‘MTOR as Regulator of Lifespan, Aging and Cellular Senescence: A Mini-Review’
Gerontology, Vol. 64, p.127.
 21C. Ross‘Metabolic Consequences of Long-Term Rapamycin Exposure on Common Marmoset Monkeys (Callithrix Jacchus)’
Aging, Vol. 7, p.964.
 Two such drugs under investigation are the immunosuppressant rapamycin22Z. Dave‘Rapamycin the Only Drug That Has Been Consistently Demonstrated to Increase Mammalian Longevity. An Update’
Experimental Gerontology, Vol. 176, p.112166.
 and metformin, a drug originally prescribed for type-2 diabetes and other metabolic diseases which had the “side effect” of reducing the incidence of other diseases of age compared with the purportedly healthy, non-diabetic controls against whom they were compared.23C. A.‘Can People with Type 2 Diabetes Live Longer than Those without? A Comparison of Mortality in People Initiated with Metformin or Sulphonylurea Monotherapy and Matched, Non-Diabetic Controls’
Diabetes, Obesity and Metabolism, Vol. 16, p.1165.

Trials of metformin and rapamycin24J. Leth‘Clinical Trials Targeting Aging’

Frontiers in Aging, Vol. 3.
suggest that these small-molecule drugs can change the biology of ageing in tissues to a younger profile. The first big, multi-centre trial is about to start.25‘TAME - Targeting Aging with Metformin’
American Federation for Aging Research.
 Another approach is senolytics, which target senescent cells before they can damage tissues, and many more drugs and natural products are being developed. Gene therapy and stem cells are other rapidly developing approaches to systemic and organ-specific rejuvenation.

Healthspan therapies and interventions - Anticipation Scores

The Anticipation Potential of a research field is determined by the capacity for impactful action in the present, considering possible future transformative breakthroughs in a field over a 25-year outlook. A field with a high Anticipation Potential, therefore, combines the potential range of future transformative possibilities engendered by a research area with a wide field of opportunities for action in the present. We asked researchers in the field to anticipate:

  1. The uncertainty related to future science breakthroughs in the field
  2. The transformative effect anticipated breakthroughs may have on research and society
  3. The scope for action in the present in relation to anticipated breakthroughs.

This chart represents a summary of their responses to each of these elements, which when combined, provide the Anticipation Potential for the topic. See methodology for more information.

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