New Horizons: Novel Approaches to Enhance Healthspan Through Targeting Cellular Senescence and Related Aging Mechanisms

Author:

Tchkonia Tamar1ORCID,Palmer Allyson K1ORCID,Kirkland James L1ORCID

Affiliation:

1. Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota

Abstract

Abstract The elderly population is increasing faster than other segments of the population throughout the world. Age is the leading predictor for most chronic diseases and disorders, multimorbidity, geriatric syndromes, and impaired ability to recover from accidents or illnesses. Enhancing the duration of health and independence, termed healthspan, would be more desirable than extending lifespan merely by prolonging the period of morbidity toward the end of life. The geroscience hypothesis posits that healthspan can be extended by targeting fundamental aging mechanisms, rather than attempting to address each age-related disease one at a time, only so the afflicted individual survives disabled and dies shortly afterward of another age-related disease. These fundamental aging mechanisms include, among others, chronic inflammation, fibrosis, stem cell/ progenitor dysfunction, DNA damage, epigenetic changes, metabolic shifts, destructive metabolite generation, mitochondrial dysfunction, misfolded or aggregated protein accumulation, and cellular senescence. These processes appear to be tightly interlinked, as targeting any one appears to affect many of the rest, underlying our Unitary Theory of Fundamental Aging Mechanisms. Interventions targeting many fundamental aging processes are being developed, including dietary manipulations, metformin, mTOR (mechanistic target of rapamycin) inhibitors, and senolytics, which are in early human trials. These interventions could lead to greater healthspan benefits than treating age-related diseases one at a time. To illustrate these points, we focus on cellular senescence and therapies in development to target senescent cells. Combining interventions targeting aging mechanisms with disease-specific drugs could result in more than additive benefits for currently difficult-to-treat or intractable diseases. More research attention needs to be devoted to targeting fundamental aging processes.

Funder

Translational Geroscience Network

National Institutes of Health

Alzheimer’s Association Part the Cloud Program

Robert and Arlene Kogod

Connor Group

Robert J. and Theresa W. Ryan

Noaber Foundation

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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