Dietary restriction and mitochondrial function link replicative and chronological aging in Saccharomyces cerevisiae

Abstract

Chronological aging of budding yeast cells results in a reduction in subsequent replicative life span through unknown mechanisms. Here we show that dietary restriction during chronological aging delays the reduction in subsequent replicative life span up to at least 23 days of chronological age. We further show that among the viable portion of the control population aged 26 days, individual cells with the lowest mitochondrial membrane potential have the longest subsequent replicative lifespan. These observations demonstrate that dietary restriction modulates a common molecular mechanism linking chronological and replicative aging in yeast and indicate a critical role for mitochondrial function in this process.

Mitochondria and aging: A role for the mitochondrial transition pore?

“…This is in accordance with data from Delaney et al. (2013) showing in yeast that cells with the lowest mitochondrial membrane potential have the longest subsequent replicative lifespan, but also with the demonstration that mild uncoupling protects mitochondrial function and contributes to the longevity of the most active human muscle fibers (Amara et al., 2007). A possible reason for this protective effect is the prevention of ROS production which is a well‐known consequence of a mild drop in membrane potential (Skulachev, 1998).…”

Dietary restriction and lifespan: Lessons from invertebrate models

“…There is also overlap between the various downstream components of DR. For example, inhibition of mTOR or Sch9 increases mitochondrial respiration and also induces stress response transcription factors that can enhance resistance to acidification-induced cell death (Bonawitz et al, 2007; Fabrizio et al, 2001; Lavoie and Whiteway, 2008; Pedruzzi et al, 2003). In addition, chronological aging leads to reduced RLS (Ashrafi et al, 1999; Delaney et al, 2013; Murakami et al, 2012), suggesting underlying mechanistic similarities between mitotic and post-mitotic lifespan within the same eukaryotic cell.…”

Microfluidic technologies for yeast replicative lifespan studies

“…Mitochondrial membrane potential has previously been implicated as a biomarker or mediator of age-related cellular pathology 42–46 . By tracking the mitochondrial membrane potential in individual cells across the aging process, Fehrmann et al found that the instantaneous risk of losing mitochondrial membrane potential did not increase with age.…”