Table 2.

Neurological findings

Spontaneous locomotor activity
Assay	Aging phenotype	Intervention	Strain, sex	Treatment effects in aged mice	Treatment effects in young mice	References
Assessment of exploratory activity in a novel environment (open field, 20 min)	Reduced exploratory activity	Aging cohorts: oral rapamycin (14 ppm) for approx. 1 year starting at 4 months, 13 months or 25 months; young animals: oral rapamycin (14 ppm) for 3 months starting at 12 weeks of age	Male C57BL/6J Rj	Increase in exploratory activity	Increase in exploratory activity	[13]
Assessment of spontaneous in-cage motor activity (for 50 h); baseline assessment at 7 months of age; animals reexamined at 18 months of age	Reduced motor activity	Oral rapamycin (14 ppm) initiated at 9 months of age	Male UM-HET3 mice	Amelioration of age-dependent reduction in motor activity (in 2 out of 3 cohorts)	Not examined	[11]
Assessment of spontaneous in-cage motor activity (for 50 h); baseline assessment at 7 months of age; animals reexamined at 18 months of age	Reduced motor activity	Oral rapamycin (4.7, 14 or 42 ppm) initiated at 9 months of age	Male and female UM-HET3 mice	Amelioration of age-dependent reduction in motor activity (significant in males given 14 ppm and females given 42 ppm)	Not examined	[18]
Voluntary wheel running (assessed for 48 h)	Not examined	Oral rapamycin (14 ppm) for 3 months started at 24 months of age	Female C57BL/6J	Increased voluntary wheel running	Not examined	[19]

Motor coordination and balance
Assay	Aging phenotype	Intervention	Strain, sex	Treatment effects in aged mice	Treatment effects in young mice	References
Accelerating rotarod	Reduced latencies to fall	Oral rapamycin (14 ppm) for approx. 1 year starting at 4, 13 or 25 months	Male C57BL/6J Rj	No effect	Not examined	[13]
Accelerating rotarod (shown are results of a 5th session after 4 sessions of training; rotarod assessment at 25 and 31 months of age)	No decline in latencies to fall between 25 and 31 months	Oral rapamycin (14 ppm) starting at 19 months of age	Male and female C57BL/6Nia mice	Increased latencies to fall at 31 months	Not examined	[22]
Accelerating rotarod		Hypomorphic mTOR allele (mTOR ∆/∆); mTOR ∆/∆ mice were compared to wildtype littermate controls; young animals were 3–6 months old; aged animals were 17–27 months old	Mixed 129S1 and C57BL/6Ncr background; male mice	Increased latencies to fall in aged mTOR ∆/∆ mice (caveat: small sample size with only 4–6 mice per group; body weight differences between mutants and controls not accounted for)	No effect	[17]
Stride width analysis		Hypomorphic mTOR allele (mTOR ∆/∆); mTOR ∆/∆ mice were compared to wildtype littermate controls; young animals were 3–6 months old; aged animals were 17–27 months old	Mixed 129S1 and C57BL/6Ncr background; female or mixed male/female groups of mice	Reduced stride width variance in aged mTOR ∆/∆ mice (caveat: small sample size with only 6 mice per group in all but 1 group)	No effect	[17]
Automated gait analysis on TreadScan apparatus (40 gait parameters were analyzed); assessment at 25, 30 and 32 months		Oral rapamycin (14 ppm) starting at 19 months of age	Male and female C57BL/6Nia mice	Increased stride length	Not examined	[22]

Muscle strength
Assay	Aging phenotype	Intervention	Strain, sex	Treatment effects in aged mice	Treatment effects in young mice	References
Grip strength analysis	Reduced grip strength	Oral rapamycin (14 ppm) for approx. 1 year starting at 4, 13 or 25 months	Male C57BL/6J Rj	No effect	Not examined	[13]
Grip strength analysis	No difference in grip strength between 25 and 31 months	Oral rapamycin (14 ppm) starting at 19 months of age	Male and female C57BL/6Nia mice	No effect	Not examined	[22]
Grip strength analysis	Reduced grip strength	Hypomorphic mTOR allele (mTOR ∆/∆); mTOR ∆/∆ mice were compared to wildtype littermate controls; young animals were 3–6 months old; aged animals were 17–27 months old	Mixed 129S1 and C57BL/6Ncr background; female or mixed male/female groups of mice	Increased grip strength in aged mTOR ∆/∆ mice (caveat: small sample size with only 4–6 mice per group in 3 out of 4 groups)	No effect	[17]

Nociception
Assay	Aging phenotype	Intervention	Strain, sex	Treatment effects in aged mice	Treatment effects in young mice	Reference
Hot plate test	Increased latencies to reaction	Oral rapamycin (14 ppm) for approx. 1 year starting at 4 months	Male C57BL/6J Rj	No effect	Not examined	[13]

Learning and memory
Assay	Aging phenotype	Intervention	Strain, sex	Treatment effects in aged mice	Treatment effects in young mice	References
Morris water maze	Increased escape latencies during training; no age effect on probe trial measures (comparing 11 months vs. 20 months old animals)	Aging cohorts: oral rapamycin (14 ppm) for approx. 7 months starting at 4 or 13 months of age; young animals: oral rapamycin (14 ppm) for 6 weeks starting at 6 months of age	Male C57BL/6J Rj	Improved probe trial performance and decreased latencies during training	Improved probe trial performance and decreased latencies during training	[13]
Morris water maze	Increased escape latencies during training; reduced target crossings and target quadrant occupancy during a probe trial	Oral rapamycin (14 ppm) for approx. 16 months starting at 2 months of age	C57BL6/129svj mice; sex not reported	Improved probe trial performance and decreased latencies during training	Not examined	[20]
Morris water maze	Not examined	Oral rapamycin (14 ppm) for 4 months starting at 4 months of age	Male C57BL/6J	Not examined	Improved probe trial performance and decreased latencies during training	[21]
Barnes maze	Increased escape latencies	Hypomorphic mTOR allele (mTOR ∆/∆); mTOR ∆/∆ mice were compared to wildtype littermate controls; young animals were 3–6 months old; aged animals were 17–27 months old	Mixed 129S1 and C57BL/6Ncr background; female groups of mice	Decreased escape latencies in the aged mutants (caveat: small sample size with some groups having only 6 mice)	No significant difference, but trend in the same direction (possible floor effect)	[17]
Object place recognition	Reduced exploration of novel object during test	Oral rapamycin (14 ppm) for approx. 7 months starting at 4 or 13 months of age	Male C57BL/6J Rj	No effect	Not examined	[13]
Context fear conditioning	No significant effect of age observed (comparing 15, 24 and 33 months old mice)	Oral rapamycin (14 ppm) for approx. 1 year starting at 4, 13 or 20–22 months of age	Male C57BL/6J Rj	Enhanced fear conditioning (lower activity suppression ratios)	Not examined	[13]