Molecular mechanisms shared between aging, age-associated diseases and human longevity

Research Project

For decades, researchers have wanted to understand the mechanisms that drive the aging process, occasionally proposing different theories. Based on the inflammaging theory widely accepted by the scientific community, proposed in 2000 by Professor Claudio Franceschi, aging and many age-associated diseases share some basic molecular mechanisms, including inflammation. As a corollary of this idea, aging could be considered as an inconstant phenomenon which does not occur in all people at the same speed; in fact, it could be slowed down, as occurs in some particularly long-lived subjects such as centenarians. In recent years our research group has investigated this theory, studying molecules called Mytokines and Perilipins, whose roles include the control of inflammation and (primarily) metabolism. Our group was the first to observe that the level of mytokines is elevated in the elderly and correlates with a shorter life expectancy (Conte et al., 2019a)—as well as having a peculiar expression in diseases such as Type II Diabetes and Alzheimer's Disease (Conte et al., 2021). Perilipins, on the other hand, are proteins that surround the intracellular fat depots called lipid droplets; they are essential for lipid metabolism and, indirectly, for the inflammatory response. We were the first to demonstrate that one of these, Plin2, is correlated with sarcopenic myosteatosis (Conte et al., 2013). In collaboration with other groups at the Universities of Padua and Pisa, we have shown that silencing the Plin2 gene modifies the composition and lipid content of muscle fibers, activating a muscle hypertrophy program (Conte et al., 2019b) .

Much remains to be discovered about these molecules, in particular the precise role (beneficial or detriemental of the chronic secretion of mytokines in aging, as well as in diseases such as Type II Diabetes, Alzheimer's Disease, sarcopenia and tumors, where a mytokine called GDF15 appears to play an important role in the induction of cancerous cachexia. As for Perilipins, they may have a role in numerous pathologies in which there is an accumulation of lipids, such as hepatosteatosis, atherosclerosis and cardiovascular diseases, and sarcopenic myosteatosis. However, there are still many gaps in our knowledge of the physiological role of these proteins in, for example, neurodegenerative diseases such as Alzheimer's Disease. Our group investigates various aspects of the biology of these molecules, trying to find a biological link between them and with some of the primary age-associated pathologies.

Updated Research Aims

We are currently interested in the characterization of the expression of Perilipins in different areas and cell types of the human brain, either healthy or affected by neurodegeneration in early stages (Early Tauopathy) or advanced (Alzheimer's Disease).

New research topics

1.  Identification of possible differences, at the mitochondrial level, between neurons from patients with Alzheimer's disease and neurons from subjects of the same age without neurodegeneration or centenarians—in terms of Mytokines and mitochondrial function parameters.
2. Study of circulating levels of Mytokines and Perilipin 2 in patients with non-small cell lung cancer.

Collaboration:

Maria Conte, team member

 Antonio Chiariello, team member

Prof. Marco Sandri, Venetian Institute of Molecular Medicine – VIMM, and Dept. of Biomedical Sciences, University of Padua, Italy.

Proff. Giuseppe Conte, Andrea Serra, Marcello Mele, Department of Agriculture, Food and Environment, Università di Pisa, and Research Center of Nutraceuticals and Food for Health (NUTRAFOOD), University of Pisa, Italy.

 Dott. Valentina Medici, Tino Emanuele Poloni, Prof. Antonio Guaita, Fondazione Golgi-Cenci, Abbiategrasso, Milan, Italy.

 Prof.ssa Daniela Monti, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, Università di Firenze.