Seven knowledge gaps in modern biogerontology

Abstract

Hayflick 2007a). This declaration was their rebuttal to a much earlier paper by the Nobel Laureate Peter Medawar that ageing was the last unsolved problem in biology (Medawar 1952). Both Holliday and Hayflick had based their proclamations on the assumption that, by the end of the twentieth century, a detailed description of the ageing phenotype at all levels of the biological organization was already achieved, possible molecular-genetic processes of longevity assurance were understood, and that explanations for the evolution of ageing and longevity were generally accepted.Since then, a tsunami of ageing interventional research publications and associated industry news has been dominating the biogerontological scene, often with naïve extrapolations, overhyped claims and empty promises. Several biogerontologists, demographers and ethicists have repeatedly drawn the attention of scientists and the general public to the pros and cons, hype and reality, fact and fiction of the socalled "anti-ageing" industry (

Intracellular cytokines in peritoneal leukocytes relate to lifespan in aging and long-lived female mice

“…Moreover, the present work highlights specific immune adaptations in long-lived individuals, which may underlie their achievement of a prolonged and healthy lifespan. At last, this research may contribute to fill in one of the seven knowledge gaps in modern biogerontology that have been recently described (Rattan 2024). In particular, this work provides one approach to help distinguishing between harmful, useful, and neutral changes occurring during ageing, that is by the study of the relationship between those changes at a given time point in the old age and lifespan.…”

Inhibition of mTOR prevents glucotoxicity-mediated increase of SA-beta-gal, p16INK4a, and insulin hypersecretion, without restoring electrical features of mouse pancreatic islets

“…Our study aims to correlate and to qualitatively characterize mechanisms of islet cell adaptation (or failure) during cell stress and induction of known senescence markers, as well as the significance of mTOR pathway for these functional and molecular alterations. This basic investigation is an essential prerequisite for addressing current knowledge gaps in biogerontology concerning the efficacy of any interventional strategy interacting with repair and recovery during the aging process (Rattan 2024). Likewise, identifying whether the generic biomarkers usually associated with senescence are applicable for the pancreatic beta-cells, which are known to possess a low replication rate, requires thorough assessment.…”

“…In the context of aging accelerated senescence may occur due to over-activation of signaling pathways such as mTOR. Certainly, this model-as all in vitro models with isolated tissue or organs-does not entirely reflect the complex dynamics of senescence-associated metabolic interactions (or failure) in the whole organism (Rattan 2024). As the induction of SA-beta-gal and the hypersecretory phenotype in response to glucotoxicity occurred in islets of male and female mice, the data of both sexes were pooled.…”

“…The reversal of insulin hypersecretion in our in vitro model is not mediated by a reversion of glucotoxicity-induced changes in the glucose-sensitivity of the classical stimulus-secretion cascade. An intriguing aspect that remains to be clarified by long-term experiments with "aged islets" at different timepoints is, whether interfering with the hypersecreting phenotype by modulating mTOR proves to be beneficial, neutral or detrimental for the dynamic regulation of blood glucose during the aging process with its heterogenous demands (Rattan 2024).…”

Altered lactate/pyruvate ratio may be responsible for aging-associated intestinal barrier dysfunction in male rats

“…Since ageing is primarily a progressive loss of health, the focus of interventional strategies requires a shift from the treatment and prevention of diseases to the maintenance, recovery and enhancement of health. The seven knowledge gaps (the species, sexes, bodily-systems, organs, cell types, organelles, and macromolecules) have significantly implications for both the basic research in biogerontology and for the success of interventional strategies being pursued for healthy ageing and longevity of human beings (Rattan 2024 ).…”