Exhibit 10.1

FIRST AMENDMENT TO LEASE

This First Amendment (the “ First Amendment ”) to Lease is made as of October 30, 2007, by and between ARE-TECH SQUARE, LLC , a Delaware limited liability company, having an address at 385 East Colorado Boulevard, Suite 299, Pasadena, California 91101 (“ Landlord ”), and SIRTRIS PHARMACEUTICALS, INC. , a Delaware corporation, having an address at 790 Memorial Drive, Cambridge, Massachusetts 02139 (“ Tenant ”).

RECITALS

A.          Landlord and Tenant have entered into that certain Lease (the “ Lease ”) dated as of June 22, 2007 (the “ Lease ”), wherein Landlord leased to Tenant certain premises (the “ Premises ”) located at 200 Technology Square, Cambridge, Massachusetts, more particularly described in the Lease.

B.           Tenant desires to expand the Premises demised under the Lease by adding 3,786 rentable square feet (the “ Expansion Space ”) in the basement portion of the Building of which the Premises are a part, and Landlord is willing to lease such portion of the Project to Tenant on the terms herein set forth.

C.           Landlord and Tenant desire to amend the Lease to, among other things, add the Expansion Space to the Premises demised under the Lease and to provide for the improvement of such space.

AGREEMENT

NOW, THEREFORE, the parties hereto agree that the Lease is amended as follows:

1.            Capitalized Terms . Capitalized terms used herein and not otherwise defined shall have the meaning thereto ascribed in the Lease.

2.            Premises . Effective upon full execution hereof by Landlord and Tenant, the definition of “Premises” set forth in the Basic Lease Provisions of the Lease is hereby amended by deleting the same and replacing it with the following:

“That portion of the Project, containing a total of approximately 47,870 rentable square feet, as determined by Landlord, consisting of approximately (i) 17,357 rentable square feet on the second (2 ^nd ) floor of the Building (“ Second Floor Space ”), (ii) 17,357 rentable square feet on the third (3 ^rd ) floor of the Building (“ Third Floor Space ”), (iii) 8,679 rentable square feet on the fourth (4 ^th ) floor of the Building (“ Fourth Floor Space ”); (iv) 471 rentable square feet on the first (1 ^st ) floor of the Building (“ First Floor Space ”) and (v) 4,006 rentable square feet of space, in the basement of the Building (the “ Basement Space ”), as shown on Exhibit A .”

Exhibit A to the Lease is hereby deleted in its entirety and replaced with Exhibit A attached hereto.

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3.            Rentable Area of Premises . It is agreed that the Rentable Area of Premises is 47,870 sq. ft. and that Tenant’s share of Operating Expenses, as of the date hereof, is 27.03%.

4.            Security Deposit .

(a)           As a condition to the effectiveness of this First Amendment, the Security Deposit as defined in the Lease shall be increased by the sum of $174,490.87, which amount shall be held by Landlord as part of the Security Deposit subject to the terms of the Lease, it being agreed that the amount subject to proportionate increase as set forth in the definition of Security Deposit in the Lease shall, for all purposes, be $2,100,296.25.

(b)           The amount by which the Security Deposit may be reduced, subject to and in accordance with the third paragraph of Section 6 of the Lease, shall be $233,366.25. Accordingly, wherever $213,978.38 appears in the third paragraph of Section 6 of the Lease, it shall be deleted and replaced by $233,366.25.

5.            Landlord’s Work .

(a)           Definition of Landlord’s Work With Respect to the Basement Space . Landlord and Tenant agree that the Work Letter attached as Exhibit C to the Lease shall be deemed to apply to all of the Premises except the Basement Space, consequently with respect to such Work Letter, Section 5(b) thereof is hereby amended by deleting the first sentence thereof and replacing the same with the following:

“ Landlord shall provide to Tenant a tenant improvement allowance (the “TI Allowance”) of $180.00 per rentable square foot of the Premises excluding the Basement Space (which, based on 43,864 rentable square feet initially demised under the Lease, excluding the Basement Space, equates to $7,895,520.00 in the aggregate).”

(b)           Improvement of Basement Space . Delivery and acceptance of the Basement Space shall be subject to and on the terms set forth in the last two paragraphs of Section 2 of the Lease, it being agreed, however, that the Work Letter attached hereto as Exhibit B shall apply with respect to the Basement Space.

6.            Commencement Date and Rent Commencement Date . The first two sentences of the second paragraph of Section 2 of the Lease are hereby amended by deleting the same and replacing them with the following:

“ The “ Commencement Date ” with respect to the Basement Space, the First Floor Space, the Second Floor Space, the Third Floor Space and the Fourth Floor Space shall be the earliest of: (i) the later of (a) December 1, 2007, (b) the date Landlord Delivers such portion of the Premises to Tenant or (c) the date Landlord could have Delivered such portion of the Premises but for Tenant Delays; and (ii) the date Tenant conducts any business in such portion of the Premises or any part thereof. The “ Rent Commencement Date ” shall be (a) the Commencement Date, with respect to each of the Basement Space, First Floor Space, Second Floor Space, and Third Floor Space, and (b) with respect

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to the Fourth Floor Space only, the earlier of (X) one year after the Commencement Date or (Y) the date Tenant conducts any business in the Fourth Floor Space or any part thereof.”

7.            Target Commencement Date . Landlord and Tenant agree, with respect to the Basement Space, only, the Target Commencement Date shall be February 15, 2008.

8.            Parking . The phrase in parentheses in the first sentence of Section 10 of the Lease, “(which, based on 44,084 rentable square feet, equates to 66 parking spaces)”, shall be deleted and replaced with “(which, based on 47,870 rentable square feet, equates to 72 parking spaces)”.

9.            Miscellaneous .

(a)           This First Amendment is the entire agreement between the parties with respect to the subject matter hereof and supersedes all prior and contemporaneous oral and written agreements and discussions. This First Amendment may be amended only by an agreement in writing, signed by the parties hereto.

(b)           This First Amendment is binding upon and shall inure to the benefit of the parties hereto and their respective permitted successors and assigns.

(c)           This First Amendment may be executed in any number of counterparts, each of which shall be deemed an original, but all of which when taken together shall constitute one and the same instrument. The signature page of any counterpart may be detached therefrom without impairing the legal effect of the signature(s) thereon provided such signature page is attached to any other counterpart identical thereto except having additional signature pages executed by other parties to this First Amendment attached thereto.

(d)           Landlord and Tenant each represent and warrant that it has not dealt with any broker, agent or other person (collectively “ Broker ”) in connection with this transaction other than Richards Barry Joyce & Partners and Cushman & Wakefield, and that no Broker other than Richards Barry Joyce & Partners and Cushman & Wakefield , who shall be paid by Landlord pursuant to a separate Agreement, brought about this transaction. Landlord and Tenant each hereby agree to indemnify and hold the other harmless from and against any claims by any Broker other than Richards Barry Joyce & Partners and Cushman & Wakefield claiming a commission or other form of compensation by virtue of having dealt with Tenant or Landlord, as applicable, with regard to this leasing transaction.

(e)           Except as amended and/or modified by this First Amendment, the Lease is hereby ratified and confirmed and all other terms of the Lease shall remain in full force and effect, unaltered and unchanged by this First Amendment. In the event of any conflict between the provisions of this First Amendment and the provisions of the Lease, the provisions of this First Amendment shall prevail. Whether or not specifically amended by this First Amendment, all of the terms and provisions of the Lease are hereby amended to the extent necessary to give effect to the purpose and intent of this First Amendment.

(Signatures on Next Page)

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IN WITNESS WHEREOF, the parties hereto have executed this First Amendment as of the day and year first above written.

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EXHIBIT A TO FIRST AMENDMENT

Description of Premises

Exhibit A

200 Technology Square

First Floor