Table 1.

Interventions shown to increase lifespan or healthspan in laboratory mouse models that may be suitable for translational Geroscience application in dogs or people.

Intervention	Mice	Dogs	People
Dietary restriction	Dietary restriction has been shown to increase lifespan in many, but not all, common laboratory mouse strains (Mulvey et al. 2014; Weindruch et al. 1986). It also improves many measures of healthspan including reduced cancer incidence, improved cognitive function, and enhanced metabolic health (Masoro 2005).	Dietary restriction of 25% has been reported to increase lifespan by about 2 years (Kealy et al. 2002; Lawler et al. 2007), improve metabolic health (Lawler et al. 2007; Richards et al. 2013), and delay immune senescence (Greeley et al. 2006) in Labrador retrievers maintained in a laboratory environment.	The effects of dietary restriction on mortality in people are unclear. Short-term controlled studies, as well as studies of individuals self- practicing dietary restriction have indicated improved metabolic and health parameters consistent with delayed aging (Fontana et al. 2004; Holloszy and Fontana 2007; Ravussin et al. 2015; Rochon et al. 2011). It is generally recognized that dietary restriction is not likely to represent a viable translational intervention for most individuals.
Rapamycin	Rapamycin has been shown to robustly increase lifespan in at least three different mouse strains and to improve healthspan measures including cognitive function, cardiac function, immune function, obesity, and cancer incidence (Johnson et al. 2015; Kaeberlein 2014).	Rapamycin has been shown to be well tolerated in dogs, improves outcome in a glycogen storage disease model (Yi et al. 2014), and is currently being tested in veterinary clinical trials as a treatment for osteosarcoma (Paoloni et al. 2010). veterinary clinical trial is underway to assess the side effect profile and effects on age-associated cardiac function following 10 weeks of rapamycin treatment in healthy elderly dogs (Kaeberlein 2015).	Rapamycin is used clinically to prevent organ transplant rejection, for some forms of cancer, and to prevent restenosis in cardiac stents (Kaeberlein 2013b). Short-term treatment with the rapamycin derivative RAD001 improves age-associated decline in immune function, as measured by antibody response to an influenza vaccine, in healthy elderly people (Mannick et al. 2014).
Metformin	Metformin is reported to increase lifespan in short-lived cancer-prone mouse strains (Anisimov et al. 2011a; Anisimov et al. 2010). Improved metabolic health and glucose homeostasis were reported in C57BL/6 mice treated with metformin at a dose that slightly extended lifespan, but a higher dose shortened lifespan in this strain (Martin-Montalvo et al. 2013).	One study found metformin to be protective against induced heart failure in a laboratory dogs (Sasaki et al. 2009). There is little data on use of metformin for diabetes in dogs. Dosing is critical, as metformin overdose can be a serious problem in dogs.	Metformin is the most widely prescribed antidiabetic drug in the world. Use of metformin has been associated with reduced cancer risk, reduced cardiovascular disease, and reduced all- cause mortality in diabetics (Bannister et al. 2014; Foretz et al. 2014). The Targeting Aging with MEtformin clinical trial has been proposed to assess whether metformin can delay comorbidity in people (Check Hayden 2015).
Acarbose	Acarbose was shown by the NIA Interventions Testing Program to robustly increase lifespan in male mice and modestly increase lifespan in female mice (Harrison et al. 2014).	Acarbose improves glucose homeostasis in diabetic dogs and is available by prescription for treatment of diabetes in dogs (Nelson 2000). To the best of our knowledge there is no published data indicating that treating dogs with acarbose can improve healthy longevity.	Acarbose is used clinically as a treatment for diabetes in people. It is more commonly used in Asia and Europe than in the United States (DiNicolantonio et al. 2015; He et al. 2014). To the best of our knowledge there is no published data indicating that treating people with acarbose can improve healthy longevity.
NAD precursors	NAD precursors such as nicotinamide riboside and nicotinamide mononucleotide have been reported to delay muscle aging and cognitive decline in mice (Gomes et al. 2013). At the time of this writing, there are no lifespan data available in mice.	To the best of our knowledge there is no published data indicating that treating dogs with NAD precursors can improve healthy longevity.	To the best of our knowledge there is no published data indicating that treating people with NAD precursors can improve health or longevity.
Resveratrol	Resveratrol increases survival of mice fed a high fat diet and is reported to improve metabolic function during aging (Baur et al. 2006). Resveratrol does not significantly increase the lifespan of mice fed a normal diet (Miller et al. 2011).	To the best of our knowledge there is no published data indicating that treating dogs with resveratrol can improve healthy longevity.	To the best of our knowledge there is no published data indicating that treating people with resveratrol can improve healthy longevity.
Sirtuin Activating Compounds	Two sirtuin activating compounds, SIRT1720 and SIRT2104, have been reported to modestly increase lifespan in inbred C57BL/6 mice and to improve measures of metabolic function during aging (Mercken et al. 2014; Mitchell et al. 2014).	To the best of our knowledge there is no published data indicating that treating dogs with sirtuin activating compounds can improve healthy longevity.	To the best of our knowledge there is no published data indicating that treating people with sirtuin activating compounds can improve healthy longevity.