"From geroscience to precision geromedicine: Understanding and managing aging"

A great resource just published in Cell by Cell Press by a stellar group of authors, Guido KROEMER, Andrea B. Maier, Ana Maria Cuervo (Albert Einstein College of Medicine), Vadim Gladyshev, Luigi Ferrucci, Vera Gorbunova, Brian Kennedy, Thomas Rando, Andrei Seluanov, Felipe Sierra, Eric Verdin and Carlos López-Otin (Universidad Nebrija).

This review article provides an outline of a roadmap from the current state of "geroscience" (defined as the field of inquiry dedicated to the identification of ACTIONABLE hallmarks of aging) to actual interventions, which the authors argue require precision medicine -"pending results from randomized clinical trials and regulatory approval, gerotherapeutics will be tailored to each person based on their genetic profile, high-dimensional omics-based biomarkers of aging, clinical and digital biomarkers of aging, psychosocial profile, and past or present exposures."

They contrast 3 different descriptive frameworks:

1️⃣ The 13/14 hallmarks of aging, biological phenomena that associate "causally" with aging (e.g., telomere attrition, epigenetic alterations, cellular senescence, stem cell exhaustion, chronic inflammation, dysbiosis) 2️⃣ Diseases of aging are probably the most familiar to the general public, e.g., cancer, cardiovascular disease, sarcopenia (muscle loss), neurodegeneration. Such diseases are related to the hallmarks in complex ways: they are in a way the emergent outcome of many interacting processes. 3️⃣ Gerogenes and gerosuppressors, involved in pathways that impact directly one or more diseases of aging. The idea is that "biological aging can be viewed as a process that is not only modulated by the environment but also accelerated by the activation of gerogenes and the inactivation of gerosuppressive genes". The identification of these genes (and their presence or absence in a patient) can lead to personalized therapeutic routes.

The picture here shows multiple genes and their involvement in a number of diseases of aging. Some have a narrow impact on one disease, but many affect more than one disease, suggesting that targeting these genes or their products may have an overall aging effect.

I will leave with this quote: "Theoretically, to obtain broad drug effects on multiple age-related diseases, at least one of two conditions should be fulfilled. Either the drug should target the root causes of several diseases, ideally the entire aging process, or, alternatively, the disease-specific process that is targeted (e.g., hyperglycemia or dyslipidemia) should be involved in disease-aggravating feedforward loops that involve several organ systems (e.g., the metabolic, cardiovascular, and immune/inflammatory systems), thus compromising general health"