Physiological frailty index (PFI): quantitative in-life estimate of individual biological age in mice.
The development of healthspan-extending pharmaceuticals requires quantitative estimation of age-related progressive physiological decline. In humans, individual health status can be quantitatively assessed by means of afrailty index(FI), a parameter which reflects the scale of accumulation of age-related deficits. However, adaptation of this methodology to animal models is a challenging task since it includes multiple subjective parameters. Here we report a development of a quantitative non-invasive procedure to estimate biological age of an individual animal by creatingphysiological frailty index(PFI). We demonstrated the dynamics of PFI increase during chronological aging of male and female NIH Swiss mice. We also demonstrated acceleration of growth of PFI in animals placed on a high fat diet, reflecting aging acceleration by obesity and provide a tool for its quantitative assessment. Additionally, we showed that PFI could reveal anti-aging effect of mTOR inhibitor rapatar (bioavailable formulation of rapamycin) prior to registration of its effects on longevity. PFI revealed substantial sex-related differences in normal chronological aging and in the efficacy of detrimental (high fat diet) or beneficial (rapatar) aging modulatory factors. Together, these data introduce PFI as a reliable, non-invasive, quantitative tool suitable for testing potential anti-aging pharmaceuticals in pre-clinical studies.
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Marina P
MP
Antoch
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.|Everon Biosciences, Inc., Buffalo, NY 14203, USA.
Michelle
M
Wrobel
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Karen K
KK
Kuropatwinski
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Ilya
I
Gitlin
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Katerina I
KI
Leonova
Everon Biosciences, Inc., Buffalo, NY 14203, USA.
Ilia
I
Toshkov
Everon Biosciences, Inc., Buffalo, NY 14203, USA.
Anatoli S
AS
Gleiberman
Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Alan D
AD
Hutson
Everon Biosciences, Inc., Buffalo, NY 14203, USA.
Olga B
OB
Chernova
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Andrei V
AV
Gudkov
D000375:Aging / Q000502:physiology*; D000818:Animals; D059305:Diet, High-Fat; D005260:Female; D006304:Health Status; D008136:Longevity / Q000502:physiology*; D008297:Male; D051379:Mice; D012727:Sex Characteristics
aging; chronological age; high fat diet; obesity; rapamycin; rapatar